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1. Phase Angle as an Indicator of Depression in Maintenance Hemodialysis Patients

Author: Xin Li, Kun Zhang, Qi Guo, Wei Ding, Jianying Niu, Junli Zhao, Liming Zhang, Hualin Qi, Suhua Zhang, and Chen Yu
Subjects: phase angle, depression, hemodialysis, bioelectrical impedance analysis, Internal medicine, RC31-1245
Abstract: Introduction: Depression is a common psychiatric problem in maintenance hemodialysis (MHD) patients. Recent studies have begun to explore the relationship between body composition and depression. Phase angle (PhA), a core parameter for assessing body composition, has been observed to be associated with frailty and cognitive dysfunction. The aim of this study was to investigate the association between PhA and depression in MHD patients. Methods: This multicenter, cross-sectional study included 843 MHD patients from seven dialysis centers in Shanghai, China. Depressive symptoms were evaluated using the Patient Health Questionnaire (PHQ-9), with a score of ≥10 indicating depression. PhA was measured by bioelectrical impedance analysis. Nutritional status was assessed by malnutrition inflammation score (MIS). Multivariable logistic regression models were used to investigate the association between PhA and depression. Restricted cubic spline (RCS) analysis was utilized to examine the association. Receiver operating characteristic curve was used to identify the cut-off value of PhA for depression. Results: A total of 15.2% of patients (62.8% male, median age 66 years) had depression. Median PhA level (interquartile range) of depressed patients was 4.4° (3.9–4.9°) for males and 3.9° (3.2–4.7°) for females. There was a significant decrease in the prevalence of depression with increasing quartiles of PhA levels. In multivariable logistic regression analyses, after adjusting for age, sex, education level, spKt/V, dialysis vintage, Charlson comorbidity index, hemoglobin, and serum albumin, lower PhA levels (lowest quartile group) were significantly associated with depressive symptoms (adjusted odds ratio, 2.19; 95% confidence interval, 1.07 to 4.48), compared to higher PhA levels (highest quartile group). RCS analysis showed a relatively inverse linear association between PhA and depression. The optimal cut-off value of PhA for depression was 4.9° for males and 3.5° for females. Subgroup analyses validated the findings across patient characteristics, including age, sex, diabetes, education, and malnutrition. Conclusion: Our findings indicated an inverse association between PhA and depressive symptoms in Chinese MHD patients, suggesting that PhA could serve as a valuable indicator for assessing the risk of depression in this population. Further studies are needed to explore the potential of PhA as a prognostic tool and its implications for intervention strategies.
Published: 2024
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2. Association between hearing loss and physical performance in patients on maintenance hemodialysis

Author: Weifeng Fan, Xiaojing Zhong, Qing Wu, Lihong Zhang, Zhenhao Yang, Yong Gu, Qi Guo, Xiaoyu Chen, Chen Yu, Kun Zhang, Wei Ding, Hualin Qi, Junli Zhao, Liming Zhang, Suhua Zhang, and Jianying Niu
Subjects: gait speed, handgrip strength, hearing loss, hemodialysis, physical performance, Internal medicine, RC31-1245, Specialties of internal medicine, RC581-951
Abstract: Background The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged
Published: 2024
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3. Lower extremity function and cardiovascular disease risk in hemodialysis patients: A multicenter cross‐sectional study

Author: Kun Zhang, Xin Li, Qi Guo, Wei Ding, Jianying Niu, Junli Zhao, Liming Zhang, Hualin Qi, Suhua Zhang, and Chen Yu
Subjects: cardiovascular disease, hemodialysis, lower extremity function, Physiology, QP1-981
Abstract: Abstract Physical performance in hemodialysis patients declines and serves as a cardiovascular disease (CVD) incidence and mortality predictor. However, lower extremity function's role remains unclear. This study aimed to quantify the association between lower extremity function and CVD risk in hemodialysis patients. This was a multicenter cross‐sectional study enrolling 868 participants (532 males, 336 females) from seven hemodialysis centers in Shanghai, China. Patients were divided into three groups per lower extremity function, evaluated by short physical performance battery (SPPB) scores: 0–6, 7–9, and 10–12. Upper extremity function was quantified through grip strength assessment. CVD risk was assessed using the Framingham Risk Score. Approximately 35% of hemodialysis patients had impaired lower extremity function (SPPB score
Published: 2024
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4. Association of physical performance with cognitive impairment in middle-aged to older haemodialysis patients: a multicentre cross-sectional observational study

Author: Jia Xu, Xinhui Zhao, Qi Guo, Cheng Yu, Wei Ding, Jianying Niu, Junli Zhao, Liming Zhang, Suhua Zhang, Hualin Qi, and Minhui Xi
Subjects: Medicine (General), R5-920
Abstract: Objective To determine the prevalence of cognitive impairment (CI) among middle-aged to older patients receiving maintenance haemodialysis (MHD) and to investigate the potential association between CI and physical performance. Methods This cross-sectional observational study enrolled participants aged 55–85 years who received MHD. Cognitive status was assessed using the Mini Mental State Examination (MMSE). Physical performance was measured by hand grip strength, the Timed Up and Go Test (TUGT) and the 4-m walking speed. Sociodemographic, clinical and laboratory parameters were recorded for each patient. Results The study included 592 patients (363 males); and of these, 126 (21.3%) were diagnosed with CI. Compared with patients with normal cognitive function, those with CI were significantly older and had significantly longer dialysis duration, lower educational level, higher Malnutrition Inflammation Score, higher depression and higher Charlson Comorbidity Index score. After adjustment for covariates, multiple regression analysis suggested that grip strength (odds ratio [OR] = 0.959, 95% confidence interval [CI] = 0.924, 0.996) and 4-m walking speed (OR = 0.161, 95% CI = 0.070, 0.368) were protective factors. TUGT (OR = 1.037, 95%CI = 1.003, 1.071) was a risk factor. Conclusion Physical performance was correlated with CI and might be a significant indicator for the early identification of CI in middle-aged to older MHD patients.
Published: 2024
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5. Effect of soluble dietary fiber on gut microbiota and derived metabolites in stage 3 to 5 chronic kidney disease patients: A randomized controlled trial

Author: Yuan Cui, Dingwei Kuang, Jing Wang, Shaoye Huo, Peng Li, Lin Lu, Yuhuan Wei, Lihong Wang, Xiaojing Zhong, Yunhua Zhao, Jianying Niu, Weibing Wang, and Chunhai Shao
Subjects: Chronic kidney disease, Soluble dietary fiber, Inflammation, Gut microbiota, Short-chain fatty acids, Nutrition. Foods and food supply, TX341-641
Abstract: Gut dysbiosis is closely associated with the burden of chronic kidney disease (CKD), and strategies such as prebiotic supplementation have been suggested to ameliorate CKD and related complications. We hypothesized that prebiotic-soluble dietary fiber (SDF) complexes could ameliorate biochemical parameters, gut microbiota and microbial metabolites of CKD. Here, forty non-dialyzed CKD patients in stage 3 to 5 were randomized to receive either SDF or placebo for 30 days. As expected, SDF intervention reduced serum total cholesterol levels (P＜0.05) and plasma interleukin (IL)-8 levels (P＜0.05). No profound changes in the diversity or community structure of the gut microbiota were observed in SDF group, but the composition of the gut microbiota was altered. Moreover, the concentration of propionate of short-chain fatty acids (SCFAs) increased significantly following SDF intervention (P＜0.05). SDF supplementation seems to be a promising strategy to improve inflammation, gut microbiology and derived metabolites.
Published: 2024
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6. Prevalence and predisposing factors of depressive symptoms in continuous ambulatory peritoneal dialysis patients: a cross-sectional single center study

Author: Yu Chen, Peng Li, Lei Zhang, Yanfei Zhang, Luyi Xie, and Jianying Niu
Subjects: Depressive symptoms, Peritoneal dialysis, Serum hemoglobin, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Abstract Background The aim of this study was to identify the prevalence of the depressive symptoms and the factors associated with the depressive symptoms in peritoneal dialysis patients. Methods A cross-sectional study was carried out to evaluate the prevalence and associated factors of depression in 132 continuous ambulatory peritoneal dialysis patients. Depression was evaluated using Zung Self-Rating Depression Scale. Sociodemographic and clinical characteristic were also investigated. Univariate analysis and multivariate logistic regression analysis were performed to select factors associated with depressive symptoms. Results Their median age was 57.5 years, and 58.3% were male. The rate of depressive symptoms in peritoneal dialysis patients was 78.0%. The rate of moderate/severe depressive symptoms was 64.4%. Multivariable logistic regression analysis showed that lower serum hemoglobin was significantly associated with increased risks of depression (OR = 0.989, 95CI%=0.979–0.998, p = 0.023). Conclusion Depression was highly prevalent in the peritoneal dialysis patients. Serum hemoglobin was independent risk factor for depressive symptoms in peritoneal dialysis patients.
Published: 2023
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7. MHC-1B carried exosomes derived from tubular epithelial cell induced by the EGFR mimotope inhibit macrophage activation in renal fibrosis

Author: Jin Guo, Xuanqi Liu, Haoming Song, Yong Gu, Jianying Niu, and Lin Yang
Subjects: Renal fibrosis, Mimotope, Exosome, Ribosomal protein L6, Major histocompatibility complex-1B, Biology (General), QH301-705.5, Medicine (General), R5-920
Abstract: The high prevalence of chronic kidney disease (CKD) is a significant public health burden worldwide. Renal fibrosis is an inevitable pathological process in almost all CKD cases. To date, the available treatments to prevent or delay renal fibrosis progression are limited. Epidermal growth factor receptor (EGFR) mimotope has been demonstrated to alleviate renal fibrosis in the unilateral ureteric obstruction (UUO) model as a type of vaccine. Further observations suggested that the EGFR mimotope can inhibit the activation of macrophages, which play a vital role in renal fibrosis. In the current study, we explored the link triggered by the EGFR mimotopes between tubular epithelial cells (TECs) and macrophages. A series of experiments indicated that EGFR mimotope immunization can inhibit the activation of THP-1 macrophages by TEC-derived exosomes. Injection of these exosomes ameliorated renal fibrosis in the UUO model. Mechanism analysis suggested that the major histocompatibility complex-1B (MHC-1B) was the key molecule in the TECs exosomes induced by EGFR mimotope immunization and is regulated by ribosomal protein L6 (RPL-6). This study revealed a new specific working path of the EGFR mimotope and suggests that the application of the EGFR mimotope can be extended to other immune-related disorders.
Published: 2023
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8. Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: A randomized, open‐label, parallel‐group, noninferiority phase III trial

Author: Bicheng Liu, Nan Chen, Jinghong Zhao, Aiping Yin, Xiongfei Wu, Changying Xing, Gengru Jiang, Junzhou Fu, Mei Wang, Rong Wang, Jianying Niu, Ping Fu, Zhaohui Ni, Fanfan Hou, Jiuyang Zhao, Jing Chen, Yuqing Chen, Wei Shi, Jianghua Chen, Wenge Li, Gang Xu, Ling Zhong, Wenhu Liu, Guohua Ding, Yuichiro Kondo, Changhe Yue, and Changlin Mei
Subjects: anemia, conversion ratio, darbepoetin alfa, epoetin alfa, hemodialysis, Medicine (General), R5-920
Abstract: Abstract Background This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis. Method This study was a multicenter, randomized, open‐label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8‐week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: −1.0 g/dl) was tested between the two treatments. The time‐dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron‐binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results Four hundred and sixty‐six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per‐protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were −0.07 and −0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: −0.22 to 0.39), and the lower limit of the 95% CI was −0.22 > −1.0 g/dl. The average Hb concentrations of the two groups were 10.88–11.43 g/dl (darbepoetin alfa) and 10.91–11.38 g/dl (epoetin alfa) during the study period of Weeks 0–28, with the maintenance rates of the target Hb concentration ranging within 71%–87% and 78%–95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis. Conclusion The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.
Published: 2022
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9. Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure: A randomized, open‐label, parallel‐group, non‐inferiority Phase III trail

Author: Nan Chen, Changying Xing, Jianying Niu, Bicheng Liu, Junzhou Fu, Jiuyang Zhao, Zhaohui Ni, Mei Wang, Wenhu Liu, Jinghong Zhao, Ling Zhong, Xiongfei Wu, Wenge Li, Yuqing Chen, Wei Shi, Jianghua Chen, Aiping Yin, Ping Fu, Rong Wang, Gengru Jiang, Fanfan Hou, Guohua Ding, Jing Chen, Gang Xu, Yuichiro Kondo, Yuliang Su, and Changlin Mei
Subjects: anemia, chronic renal failure, darbepoetin alfa, hemodialysis, recombinant human erythropoietin, Medicine (General), R5-920
Abstract: Abstract Background Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0–12.0 g/dL) for the treatment of renal anemia. Methods Ninety‐five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (n = 95) aged 18–70 years were randomized into a once per week intravenous darbepoetin alfa group (n = 56) and a twice or three times per week intravenous epoetin alfa group (n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA‐naive (erythropoiesis stimulating agent‐naive). The primary efficacy profile was the mean Hb level (the non‐inferiority margin was −1.0 g/dL, week 21–28); the secondary efficacy profiles were the Hb increase rate (week 0–4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>−1.0 g/dL), and non‐inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis. Conclusion Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.
Published: 2022
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10. Heparanase promotes endothelial-to-mesenchymal transition in diabetic glomerular endothelial cells through mediating ERK signaling

Author: Kaili Chang, Qiyuan Xie, Jianying Niu, Yong Gu, Zhonghua Zhao, Fengxia Li, Qiaojing Qin, and Xueguang Liu
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract: Abstract Glomerular endothelial cells (GEnCs) dysfunction occurs at the early stage of diabetic nephropathy (DN). One of its characteristics is endothelial-to-mesenchymal transition (EndMT). Heparanase (HPSE) is the only known mammalian endoglycosidase capable of degrading heparin sulfates and has a prominent role in DN pathogenesis. However, whether HPSE induces EndMT of GEnCs remains unknown. This study aimed to determine the effect and potential mechanism of HPSE on GEnCs phenotype under high-glucose conditions. In the early development of streptozotocin (STZ)-induced diabetic mice, HPSE overexpression was positively correlated with renal injury and the number of GEnCs undergoing EndMT, which was characterized by loss of endothelial marker CD31 and gain of mesenchymal markers including α-SMA and Snail1/2 by double immunofluorescence staining. Bioinformatics analysis revealed a positive correlation between HPSE and ERK. The counts of double positive staining of CD31 and p-ERK1/2 was significantly increased in the glomeruli of STZ-induced diabetic mice compared with sham mice. In cultured GEnCs, high glucose dramatically upregulated the expressions of HPSE and p-ERK1/2, both of which were markedly blocked by HPSE siRNA. Furthermore, recombinant mouse HPSE (rmHPSE) promoted the expressions of mesenchymal markers and p-ERK1/2 in a dosage- and time-dependent manner. U0126, a specific MEK/ERK inhibitor, significantly inhibited either high glucose or rmHPSE-induced EndMT of GEnCs. These data indicate that high glucose induces EndMT of GEnCs at least partially through upregulating HPSE and that HPSE promotes EndMT of GEnCs via activating ERK signaling. This study improves understanding the crucial role of HPSE in DN development and progression.
Published: 2022
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11. Comparison of three nutritional screening tools for detecting sarcopenia in patients with maintenance hemodialysis

Author: Xiaoyu Chen, Peipei Han, Xiaoyan Zhu, Peiyu Song, Yinjiao Zhao, Hui Zhang, Chen Yu, Jianying Niu, Wei Ding, Junli Zhao, Liming Zhang, Hualin Qi, Suhua Zhang, and Qi Guo
Subjects: dynapenia, geriatric nutritional risk index, hemodialysis, nutritional screening tool, pre-sarcopenia, sarcopenia, Public aspects of medicine, RA1-1270
Abstract: BackgroundMalnutrition, dynapenia, and sarcopenia are prevalent conditions among patients with maintenance hemodialysis (MHD). They are related to numerous adverse health outcomes. The aim of this study was to compare the effect of three nutritional screening tools on predicting the risk of dynapenia and sarcopenia in patients with MHD.MethodsFrom July 2020 to April 2021, a total of 849 patients with MHD were enrolled at seven different healthcare facilities in Shanghai, China in this multi-center cross-sectional study. Geriatric nutritional risk index (GNRI), malnutrition inflammation score (MIS), and creatinine (Cr) index were used for nutritional assessment. The cutoff values of muscle mass and strength to define dynapenia, pre-sarcopenia, and sarcopenia were based on the consensus by the Asia Working Group of Sarcopenia in 2019.ResultsAmong 849, almost 60% were malnourished with the majority suffering from dynapenia (27.7%), followed by sarcopenia (22.7%), and pre-sarcopenia (6.2%).The area under the receiver–operating characteristic curve for GNRI was 0.722 [95% confidence interval (CI) = 0.684–0.760] and 0.723 (95% CI = 0.663–0.783) in predicting sarcopenia and pre-sarcopenia. The GNRI [odds ratio (OR) =6.28, 95% CI: 4.05–9.73], MIS (OR =1.91, 95% CI: 1.31–2.78), and the Cr index (OR =2.73, 95% CI: 1.71–4.34) were all significantly associated with the risk of sarcopenia. More importantly, the sarcopenia predictability of the GNRI appears greater than the MIS and Cr index, while MIS was similar to the Cr index. Similarly, the superiority of GNRI prediction was also found in pre-sarcopenia, but not in dynapenia.ConclusionAll the three nutritional screening tools were significantly associated with an increased risk of sarcopenia. The sarcopenia predictability of the GNRI was greater than the MIS and Cr index.
Published: 2022
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12. Different stages of chronic kidney disease are associated with physical performance in adults over 60 years

Author: Peiyu Song, Xinghong Xu, Yinjiao Zhao, Minghong Gu, Xiaoyu Chen, Hui Zhang, Xinze Wu, Chen Yu, Jianying Niu, Wei Ding, Suhua Zhang, and Qi Guo
Subjects: sarcopenia, chronic kidney disease, muscle mass, muscle function, older adults, Public aspects of medicine, RA1-1270
Abstract: Objective:The purpose of this study was to determine the association between different stages of chronic kidney disease (CKD) and sarcopenia and its components in the Chinese older population.MethodsThe study comprised of 2,213 participants aged ≥ 60 years (1,025 men; mean age: 70.7 years) recruited from Shanghai who were invited to participate in a comprehensive geriatric assessment. Sarcopenia was defined according to the AWGS 2019 consensus update on sarcopenia diagnosis criteria. The glomerular filtration rate (GFR) was estimated using the equation that originated from the CKD-EPI equation, the stages of CKD are classified according to the Kidney Disease—Improving Global Outcomes (KDIGO).ResultsThe overall prevalence of sarcopenia was 19.0%, which increased with the severity of CKD. The prevalence of sarcopenia in patients with CKD 3–4 and kidney failure was significantly higher than that in normal and CKD 1–2 (p < 0.05). In logistic regression analysis model, compared with normal and CKD 1 patients, kidney failure was significantly associated with the increased risk of sarcopenia and low grip strength (p < 0.05); CKD 2, CKD 3–4 and kidney failure groups were significantly associated with an increased risk of low walking speed (p < 0.05), respectively; while the association between CKD and muscle mass was not shown.ConclusionsIn our study, only decreased physical performance, as represented by walking speed, was significantly associated with increased CKD severity. This may improve the evidence for the prevention and intervention of sarcopenia in patients with CKD.
Published: 2022
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13. Relationship between physical performance and mild cognitive impairment in elderly hemodialysis patients is modified by the presence of diabetes: A multicenter cross-sectional study

Author: Yinjiao Zhao, Peiyu Song, Chan Zhu, Lingyun Zhang, Xiaoyu Chen, Hui Zhang, Peipei Han, Wei Ding, Jianying Niu, Junli Zhao, Xiang Shao, Liming Zhang, Chen Yu, Jia Xu, Chenghu Fang, and Qi Guo
Subjects: mild cognitive impairment, diabetes, physical performance, walking speed, hemodialysis, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: ObjectiveThe purpose of this study was to observe the relationship between physical performance and mild cognitive impairment (MCI) in the presence or absence of type 2 diabetes in elderly hemodialysis patients.MethodsIn this multicenter cross-sectional study, 396 clinically stable and aged ≥60 years hemodialysis patients (255 men; mean age: 68.3 ± 5.9 years) were included from seven dialysis units in Shanghai, China. The Chinese version of the Modified Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale were utilized to assess MCI. The performance-based assessments consisted of three physical tests, grip strength (GS), Timed Up and Go Test (TUGT), and 4-m walking test, which respectively represent muscle strength, mobility, and walking speed (WS). Logistic regression and multivariate linear regression were used for analysis.ResultsHemodialysis patients with diabetes had a high prevalence of MCI (20.6%). The odds ratio (OR) of MCI for the interacted items [(TUGT) * (diabetes) and (WS) * (diabetes)] was significant (p 0.05). Further analysis showed that TUGT was negatively associated with attention and calculation and language. WS was positively associated with recall and language in diabetic hemodialysis patients.ConclusionsPhysical performance was associated with MCI in diabetic hemodialysis patients rather than the non-diabetes group. Whether increasing mobility or WS can positively influence MCI in individuals with type 2 diabetes requires further study.
Published: 2022
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14. Curcumin attenuates angiotensin II‐induced podocyte injury and apoptosis by inhibiting endoplasmic reticulum stress

Author: Nan Yu, Lin Yang, Lilu Ling, Yuan Liu, Ying Yu, Qing Wu, Yong Gu, and Jianying Niu
Subjects: angiotensin II, CKD, curcumin, ER stress, podocyte, Biology (General), QH301-705.5
Abstract: Podocytes are an important component of the glomerular filtration barrier in the kidneys. The dysfunction and apoptosis of podocytes are important factors that can lead to the progression of chronic kidney disease (CKD). In CKD, angiotensin II is continuously elevated in circulation and is considered to have key roles in inducing podocyte injury and apoptosis. Curcumin is a hydrophobic polyphenolic compound extracted from turmeric. Increasing evidence demonstrates that curcumin has a protective effect on the kidneys in CKD. However, the mechanisms mediating this protective effect remain unclear. The aim of this study was to explore whether curcumin could protect against angiotensin II‐induced injury and apoptosis of podocytes. We performed western blotting, immunofluorescence, phalloidin staining, and terminal deoxynucleotidyl transferase nick‐end labeling staining to observe the expression level of podocyte‐specific proteins, apoptosis‐related proteins, and the arrangement of F‐actin. We found that curcumin could reverse angiotensin II‐induced podocyte injury and apoptosis in a dose‐dependent manner. In addition, curcumin dose‐dependently attenuated a pro‐apoptotic pathway, activated by angiotensin II‐induced endoplasmic reticulum stress. Conversely, the protective effects of curcumin were impaired upon addition of tunicamycin, an activator of endoplasmic reticulum stress. Thus, we speculate that curcumin protects against angiotensin II‐induced podocyte injury and apoptosis, at least partly by inhibiting endoplasmic reticulum stress.
Published: 2020
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15. Empagliflozin Ameliorates Preeclampsia and Reduces Postpartum Susceptibility to Adriamycin in a Mouse Model Induced by Angiotensin Receptor Agonistic Autoantibodies

Author: Ruonan Zhai, Yuan Liu, Jiahao Tong, Ying Yu, Lin Yang, Yong Gu, and Jianying Niu
Subjects: preeclampsia, empagliflozin, autoantibody against angiotensin II type 1 receptor, podocyte, oxidative stress, Therapeutics. Pharmacology, RM1-950
Abstract: Preeclampsia (PE) is the leading cause of maternal and perinatal morbidity and mortality and also is a risk factor for cardiovascular and kidney disease later in life. PE is associated with oversecretion of autoantibodies against angiotensin II type 1 receptor (AT1-AA) by the placenta into the maternal circulation. Here, we sought to determine the therapeutic value of the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (EMPA) in mice with AT1-AA-induced preeclampsia. Pregnant mice were injected with AT1-AA at gestation day (GD) 13 and treated daily with EMPA until GD 19, at which point some of the maternal mice were sacrificed and assessed. The other maternal mice were labored on time and challenged with adriamycin (ADR) at 12 weeks postpartum; their offspring were assessed for fetal outcomes. We showed that EMPA treatment significantly relieved high systolic blood pressure and proteinuria and ameliorated kidney injury in PE mice without affecting fetal outcomes. EMPA also ameliorated podocyte injury and oxidative stress, reduced the expression of SGLT2 and activated the AMPK/SIRT1 signaling pathway in vivo and in vitro. Remarkably, EMPA treatment during pregnancy reduced ADR-induced kidney and podocyte injury postpartum. These findings suggest that EMPA could be a potential pharmacological agent for PE.
Published: 2022
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16. Revised Equations to Estimate Glomerular Filtration Rate from Serum Creatinine and Cystatin C in China

Author: Min Yang, Yonghua Zou, Tong Lu, Yule Nan, Jianying Niu, Xin Du, and Yong Gu
Subjects: Serum cystatin C, Serum creatinine, Estimated glomerular filtration rate, Chronic kidney disease, Dermatology, RL1-803, Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Aim: Our previous study demonstrated that the cystatin C-based chronic kidney disease (CKD)-EPI equation and combined by serum creatinine (CKD-EPIscr-cys) had better capability to accurately evaluate glomerular filtration rate in the CKD participants. Considering that the accuracy of estimated glomerular filtration rate (eGFR) remains less ideally, it is essential to modify the equation by including the Chinese eGFR racial factor in order to improve its performance. Methods: Two prospective cohorts were enrolled in 2 medical centers. New equations were developed in 529 participants and validated in 313 participants. Reference glomerular filtration rate (rGFR) was taken by 99mTc-DTPA renal dynamic imaging method (Gates method). The primary outcomes of this study were bias, precision (interquartile range of difference [IQR]), and accuracy (the proportion of eGFR within 30% of rGFR [P30] and root mean square error [RMSE]) of eGFR versus rGFR. Results: In a development data set, Chinese coefficients for CKD-EPIscr (C-CKD-EPIscr), CKD-EPIcys (C-CKD-EPIcys), and CKD-EPIscr-cys (C-CKD-EPIscr-cys) were 0.871, 0.879, and 0.891, respectively. In a validation data set, C-CKD-EPIcys was the most accurate with highest P30 value (62.3%), relative lowest IQR (15.45), and RMSE (0.80) among 6 equations, though the bias of C-CKD-EPIcys was not better than CKD-EPIcys. C-CKD-EPIscr and C-CKD-EPIscr-cys equations were improved in bias (p < 0.001), precision, and accuracy (p = 0.004 and
Published: 2019
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17. Undernutrition when young and the risk of poor renal function in adulthood in women with diabetes in Shanghai, China

Author: Qiaojing Qin, Kaili Chang, Qing Wu, Weifeng Fan, Yong Gu, Jianying Niu, and Xueguang Liu
Subjects: Medicine (General), R5-920
Abstract: Objective To evaluate the effect of undernutrition when young on the risk of poor renal function in adulthood in women with diabetes mellitus. Methods We studied diabetic women born between 1921 and 1958 who were exposed to the 1959-to-1962 Chinese famine when they were 0 to 37 years old. Exposure age was classified as young adulthood (18 to 37 years), adolescence (10 to 17 years), or childhood (0 to 9 years). The Adolescence group, which was provided with the largest amount of food during the famine, was used as the control group, and variance and binary logistic regression analyses were performed. Results The prevalences of low estimated glomerular filtration rate (eGFR) in the Childhood, Adolescence, and Young adulthood groups were 5.26%, 22.39%, and 79.24%, respectively. The risk of low eGFR for the Young adulthood group (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.10, 2.48), but not for the Childhood group (OR 1.10, 95% CI 0.68, 1.78), was higher than that for the Adolescence group after adjustment for potential confounders. Conclusions Undernutrition during young adulthood significantly increases the risk of renal dysfunction in adult women with diabetes. Therefore, the nutrition of less affluent young women should be improved.
Published: 2021
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18. Correction: Heparanase promotes endothelial-to-mesenchymal transition in diabetic glomerular endothelial cells through mediating ERK signaling

Author: Kaili Chang, Qiyuan Xie, Jianying Niu, Yong Gu, Zhonghua Zhao, Fengxia Li, Qiaojing Qin, and Xueguang Liu
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Published: 2022
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19. Angiotensin II Type I Receptor Agonistic Autoantibody Induces Podocyte Injury via Activation of the TRPC6- Calcium/Calcineurin Pathway in Pre-Eclampsia

Author: Ying Yu, Lihong Zhang, Guang Xu, Zhenghong Wu, Qian Li, Yong Gu, and Jianying Niu
Subjects: Pre-eclampsia, Podocyte, Angiotensin II type I receptor agonistic autoantibody /AT1-AA, TRPC6, Calcium/calcineurin, Dermatology, RL1-803, Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Background/Aims: Angiotensin II type I receptor agonistic autoantibody (AT1-AA) is closely related to pre-eclampsia, which is characterized by proteinuria and hypertension. AT1-AA has been shown to enhance the effect of AngII in pre-eclampsia, such as production of endothelin-1, activation of ROS, and vasoconstriction, which are considered to be associated with hypertension; however, whether or not AT1-AA participates in podocyte damage leading to the generation of proteinuria has not been reported. In this study we investigated the role of pre-eclamptic serum AT1-AA on podocytes and the mechanism underlying the generation of proteinuria. Methods: The levels of AT1-AA isolated from pre-eclamptic sera were determined by an enzyme-linked immunosorbent assay. Human podocytes were cultured in vitro and treated with various concentrations of AT1-AA. Whether or not an ERK1/2 inhibitor and TRPC6 siRNA inhibit the effect of AT1-AA on podocytes was determined. Western blot was used to detect the expression of podocyte-specific proteins (nephrin, synaptopodin, and podocin) and the phosphorylation of ERK1/2 and TRPC6. The arrangement of F-actin was observed by immunofluorescence. A Calcineurin Cellular Activity Assay Kit was used to detect calcineurin activity. Changes in the intracellular Ca2+ concentration was determined by confocal laser. Results: AT1-AA induced a decrease in podocyte-specific protein expression and calcineurin activity and increased expression of p-ERK1/2 and TRPC6 protein and the intracellular Ca2+ concentration. Immunofluorescence revealed rearrangement of F-actin. PD98059, an inhibitor of ERK1/2, and TRPC6 siRNA attenuated the decreased expression of podocyte-specific proteins and decreased intracellular Ca2+ concentration. The expression of TRPC6 was reduced following the addition of ERK1/2 inhibitor. Conclusion: AT1-AA induced podocyte damage in a dose-dependent manner. The underlying mechanism might involve activation of the TRPC6 –calcium/calcineurin pathway. This study provides new details regarding podocyte injury and the mechanism underlying the generation of proteinuria in pre-eclampsia.
Published: 2018
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20. Protective Effects of Glucagon-Like Peptide-1 Analog on Renal Tubular Injury in Mice on High-Fat Diet

Author: Honglei Guo, Hongmei Li, Bin Wang, Wei Ding, Lilu Ling, Min Yang, Yong Gu, and Jianying Niu
Subjects: GLP-1, ERS, Apoptosis, AT1R, Renal tubular, Physiology, QP1-981, Biochemistry, QD415-436
Abstract: Aims: The study aimed to investigate the renoprotective effect of glucagon-like peptide-1 (GLP-1) against renal tubular injury in C57BL/6 mice induced by a high-fat diet (HFD). Methods: Twenty C57BL/6 mice were fed HFD for 12 weeks. Ten of these mice were treated with GLP-1 at 200 µg/kg subcutaneously twice daily for 4 weeks (HFDG group), and the other ten mice received vehicle only (HFD group). Ten mice fed standard rodent chow served as controls (Con group). Body weight, kidney weight, food intake, and systolic blood pressure were measured. The expression of endoplasmic reticulum stress (ERS) markers (BIP, p-eIF2α, ATF4, and CHOP) and apoptosis in the kidney were examined utilizing western blotting, immunohistochemistry and TUNEL, respectively. Angiotensin II and angiotensin II type 1 receptor (AT1R) were examined by ELISA. Human proximal tubule epithelial cells (HK2) were treated with GLP-1(150 nM) followed by treatment with palmitic acid (500 nM [PA]) for 24 h. HK2 cells treated with BSA were used as controls. The protein levels of ERS markers, apoptosis-associated protein, and AT1R were measured by western blotting. Results: Increase of body weight, food intake, and systolic blood pressure was less pronounced in GLP-1 treated HFDG mice compared to HFD mice. The levels of ERS markers (BIP, p-eIF2α, ATF4, and CHOP) and apoptosis decreased following GLP-1 treatment in vivo and in vitro (p
Published: 2017
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21. The Correlation between Serum Uric Acid and Renal Function in Elderly Chinese Diabetes with Normoalbuminuria

Author: Qiaojing Qin, Yingjun Qian, Guanghua Zhu, Weifeng Fan, Jianying Niu, and Yong Gu
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Objective. The elder diabetic patients increases rapidly in China and often accompany with hyperuricemia. Recently evidences show that renal function has been impaired in part of diabetic patients with normoalbuminuria. Therefore, we investigated the relationship between serum uric acid (SUA) and renal function in Chinese elder diabetes with normoalbuminuria. Methods. The physical examination data from 1052 cases of diabetic residents with normoalbuminuria aged 70 years and over in the Jiangchuan community of Minhang District, Shanghai, from October 2011 to September 2014 was analyzed retrospectively. Each received height, body weight, waist circumference (WC), waist-to-hip ratio (WHR), blood pressure (BP), and collected samples of fasting blood and morning urine to detect blood routine, blood glucose, glycosylated hemoglobin (HbA1c), blood lipids, serum creatinine, urinary albumin, urine creatinine, and urine PH value. Correlation between SUA and renal function, an index of which is estimated using estimated glomerular filtration rate (eGFR), was analyzed. Results. The prevalence of hyperuricemia was 21.10%. Levels of WC and triglyceride (TG) increased and the levels of HbA1c, high density lipoprotein-cholesterol (HDL-C), eGFR, and urine PH decreased while the levels of SUA increased. Moreover, negative correlation of eGFR with age, WC, leukocyte, and SUA (Pearson r=0.415) was observed via Pearson correlation analysis. It indicates the strong association between SUA and eGFR. Furthermore, eGFR independently associated with SUA, age, leukocyte, hemoglobin (Hb), and fasting blood glucose (FBG) was confirmed by multiple linear stepwise regression analysis. Conclusion. SUA may play an important role in the decrease of eGFR in elderly Chinese diabetic patients with normoalbuminuria.
Published: 2019
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22. Astragalus membranaceus Extract Activates Immune Response in Macrophages via Heparanase

Author: Qiaojing Qin, Jianying Niu, Zhaoxia Wang, Wangjie Xu, Zhongdong Qiao, and Yong Gu
Subjects: Astragalus membranaceus extract, macrophage, heparanase, migration, immune response mediator, immune response, Organic chemistry, QD241-441
Abstract: Astragalus membranaceus (AM), a traditional Chinese medicinal herb, has immunoregulatory properties in many diseases. We investigated the effects and mechanism of Astragalus membranaceus extract (AME) in the macrophage migration and immune response mediator release. The viability of Ana-1 macrophages treated with AME was evaluated by the MTT method. The secretion and mRNA levels of IL-1β and TNF-a were measured by ELISA and RT-PCR, respectively. Macrophage migration was assayed by transwell assay. The activity of heparanase (HPA) was determined by a heparin-degrading enzyme assay. Our results didn’t show any toxicity of AME in macrophages. AME increased the activity of HPA, cell migration, mRNA levels and secretion of IL-1β and TNF-a in macrophages. Pretreatment with anti-HPA antibody reduced cell migration, secretion of IL-1β and TNF-a did not change the mRNA levels of IL-1β and TNF-a significantly in AME-treated macrophages. This suggests that AME may increase the release of immune response mediator and cell migration via HPA to activate immune response in macrophages.
Published: 2012
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23. Development and validation of a diagnostic nomogram for sarcopenia in Chinese hemodialysis patients

Author: Danshu, Xie, Qin, Zhu, Jianxin, Lu, Chun, Hu, Jianying, Niu, Chen, Yu, Junli, Zhao, Liming, Zhang, Hualin, Qi, Suhua, Zhang, Qi, Guo, Feng, Ding, and Wei, Ding
Subjects: Transplantation, Nephrology
Abstract: Background Sarcopenia is a clinical condition that is common in patients with chronic kidney disease (CKD), especially in those on dialysis. However, the relatively complicated diagnostic procedure limits its use in clinical situations. In this study we aimed to establish a simplified tool for the diagnosis of sarcopenia in patients on hemodialysis (HD). Methods Overall, 757 eligible patients from seven HD centers in Shanghai and Suzhou, China, were recruited from 2020 to 2021. The cross-sectional data were analyzed. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 criteria. Among them, 511 consecutive patients (77 with and 434 without sarcopenia) from five centers were included in the training set for the establishment of a diagnostic nomogram. Ten investigative parameters including clinical characteristics, body measurements and physical performance were used to derive the diagnostic nomogram. A total of 246 consecutive patients (47 with and 199 without sarcopenia) were included for validation of the diagnostic model. Results The average age of the enrolled patients was 60.4 ± 12.1 years, 59.8% were males and 90.5% received dialysis using an arteriovenous fistula. Overall, the sarcopenia rate was 16.4%. The training and validation sets showed no significant differences in sarcopenia rate (15.1% and 19.1%, respectively; P = .160). The nomogram derived from the training set for sarcopenia, which was based on only four features—age, sex, body weight and grip strength—achieved high C-indexes of 0.929 [95% confidence interval (CI) 0.904–0.953] and 0.955 (95% CI 0.931–0.979) in the training and external sets, respectively, and had a well-fitted calibration curve. The cut-off value was 0.725, with a sensitivity of 0.909 and a specificity of 0.816. The nomogram accurately diagnosed sarcopenia with fewer variables and more simplified diagnostic procedures. Conclusions The nomogram had a good diagnostic capability for sarcopenia in patients on HD and may be a convenient tool for clinical use.
Published: 2022
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24. Angiotensin 1-7 and its analogue decrease blood pressure but aggravate renal damage in preeclamptic mice

Author: Yuan, Liu, Ruonan, Zhai, Jiahao, Tong, Ying, Yu, Lin, Yang, Yong, Gu, and Jianying, Niu
Subjects: General Veterinary, Guinea Pigs, Blood Pressure, General Medicine, Receptor, Angiotensin, Type 1, General Biochemistry, Genetics and Molecular Biology, Mice, Pre-Eclampsia, Pregnancy, Humans, Animals, Female, Animal Science and Zoology, Angiotensin I
Abstract: Preeclampsia (PE) is a multisystem disease that affects the health of both the pregnant women and the fetus during pregnancy. Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) play a significant role in the pathogenesis of PE. This study aimed to determine the effects of Angiotensin 1-7 (Ang 1-7) and its analogue AVE0991 on AT1-AA-induced PE model. Pregnant mice were divided into five groups: the normal pregnant group, AT1-AA-induced preeclampsia group, and AT1-AA-induced preeclampsia group treated with Losartan, Ang 1-7, and AVE0991, respectively. AT1-AA-induced PE model was established on gestational day 13 by tail intravenous injection of purified AT1-AA polyclonal antibody from serum of guinea pigs. Blood urea nitrogen (BUN), urine albumin and urinary creatinine were measured on day 18 of pregnancy. The systolic blood pressure (SBP) was measured from gestational day 13 to day 18. Renal structure changes were observed via light and electron microscopy. Compared with the normal pregnant group (NP group), AT1-AA-induced preeclampsia group (PE group) exhibited elevated blood pressure and proteinuria, consistent with the characteristics of PE. Ang 1-7 or AVE0991 treatment decreased blood pressure without showing renoprotective effects. The findings indicated that Ang 1-7 and its analogue reduced blood pressure but aggravated renal damage in AT1-AA-induced PE mice.
Published: 2022
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25. Empagliflozin in Patients with Chronic Kidney Disease

Author: Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela 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Irina, Rump, Lar, Stegbauer, Johanne, Pötz, Christine, Schemmelmann, Mara, Schmidt, Claudia, Koch, Michael, Aker, Sendogan, Küpper, Annika, Martin, Manuela, Pfab, Thiemo, Albert, Christian, Haase, Michael, Zander, Barbara, Schneider-Danwitz, Claudia, Seeger, Wolfgang, Seeger, Wolf-Adam, Zemann, Britta, Stellbrink, Christoph, Marx, Kristin, Stellbrink, Ekaterina, Brettschneider, Britta, Watson, Stephanie, Iselt, Marion, Klausmann, Gerhard, Kummer, Inga-Nadine, Kutschat, Auguste, Streitenberger, Simone, Girndt, Matthia, Markau, Silke, Girakossyan, Ina, Hanf, Claudia, Beige, Joachim, Wendt, Ralph, Schmidt, Ulrike, Schneider, Andrea, Veelken, Roland, Donhauser, Claudia, Becker, Lui, Miftari, Nexhat, Wolfling, Ricarda, Morlok, Sarah, Hugo, Christian, Paliege, Alexander, Passauer, Jen, Stumpf, Julian, Fleischer, Annegret, Haaser, Kerstin, Kraemer, Bernhard, Jochims, Jan, Kruger, Bernd, Foellinger, Claudia, Reisler, Anastassiya, Strutz, Frank, Haack, Stefan, Hohenstatt, Ursula, Busch, Martin, Herfurth, Konstantin, Wolf, Gunter, Paul, Rainer, Haller, Hermann, Kaufeld, Jessica, Menne, Jan, Bahlmann-Kroll, Elisabeth, Bergner, Angela, Weihprecht, Horst, Er, Aydin, Sonntag, Florian, Turan, Elif, Wittmann, Michael, Klauser, Franziska, Voigt, Eva, Schettler, Volker, Schulz, Egbert, Rohnstock, Madlen, Schettler, Elke, Schroppel, Bernd, van Erp, Rene, Kachele, Martin, Ludwig, Ulla, Schulte-Kemna, Lena, Kmietschak, Waltraud, Preiss, Elke, Ruocco, Martina, Heine, Gunnar, Brzoska, Martin, Gabel, Sebastian, Büttner, Christina, Sabarai, Asma, Banas, Bernhard, Bergler, Tobia, Ehrl, Yvonne, Putz, Franz, Schuster, Antonia, Kuhn, Stefanie, Schramm, Torsten, Degenhardt, Stefan, Schmidt, Gerhard, Weiland, Lea, Giebeln-Hudnell, Ulrike, Kielstein, Jan, Eden, Gabriele, Fuchs, Brigitte, Morig, Gina, Winkler, Manuela, Darius, Harald, Kriatselis, Charalampo, Roesch, Carl-Philipp, Maselli, Astrid, Alscher, Dominik, Ketteler, Marku, Schanz, Moritz, Schricker, Severin, Rettenmaier, Bianka, Schwab, Andrea, Pergola, Pablo, Leal, Irene, Cagle, Melissa, Romo, Anna, Torres, Anthony, Joshi, Sucharit, Barrett, Kulli, Africano, Alexi, Dodds, Vicki, Gowen, Dorleena, Morris, Ashlee, Fernandez, Juan, Jimenez, Guillermo, Viera, Ricardo, Bruce, Kendaling, Barrios, Ryan, Garcia, Maylin, Garcia, Kerelyn, Leal, Iradi, Tietjen, David, Bains, David, Castillo, Carlo, Brewer, Genielle, Davis, Justin, Freking, Natalie, Golson, Brittany, Ham, Sally, Roesch, Jesslyn, Suchinda, Pusadee, Beigh, Shameem, Lilavivat, Usah, Bilton, Joyce, Bocchicchia, Kim, Turner, Jeffrey, Dahl, Neera, Peixoto, Aldo, Kavak, Yasemin, Liberti, Lauren, Nair, Hari, Page, Nicola, Rosenberg, Stephanie, Simmons, Kathryn, Isakova, Tamara, Frazier, Rebecca, Mehta, Rupal, Srivastava, Anand, Fox, Patrick, Hecktman, Jonathan, Hodakowski, Alexander, Martinez, Carlo, Phillips, Rachel, Stevenson, Alexi, Mustafa, Reem, Jansson, Kyle, Kimber, Cassandra, Stubbs, Jason, Tuffaha, Ahmad, Yarlagadda, Sri, Griffin, Debbie, Laundy, Elisabeth, Tang, Zhuo, Alicic, Radica, Cooper, Ann, Davis, Lisa, Gore, Ashwini, Goldfaden, Rebecca, Harvill, Leslie, Hichkad, Lisa, Johns, Barry, Jones, Thoma, Merritt, Kayla, Sheldon, Jennifer, Stanfield, Jennifer, Alexander, Lindsay, Preston, Kaitlyn, Wood, Lindsey, Pradhan, Rajesh, Deraad, Roger, Mcintosh, Kelli, Raymond, Loui, Shepperd, Michael, Mclaughlin, Susan, Seifert, Mary, Shepherd, Andrew, Aiello, Joseph, Durham, William, Loudermilk, Laurie, Manley, John, Burnette, Sabrina, Evans, Stephanie, Johnson, Tara, Sloan, Lance, Ann Acosta, Judy, Gillham, Stacy, Sloan, Katia, Squyres, Sueann, Rocco, Michael, Hawfield, Amret, Bagwell, Ben, Richmond, Lauren, Soufer, Joseph, Clarke, Subha, Aliu, Amanda, Calabrese, Kristine, Davis, Amanda, Poma, Veronica, Spinola, Tracy, Magee, Jame, Silva, Ricardo, Choksi, Rushab, Dajani, Lorraine, Evans, John, George, Anil, Krish, Prasanth, Martins, Gerard, Sheikh-Ali, Mae, Sutton, David, Driver, Freda, Hanburry, Abraham, Hume, Laura, Hurst, Amber, Taddeo, Matthew, Turner, Marla, Yousif, Veronica, Beddhu, Srinivasan, Al-Rabadi, Laith, Abraham, Nikita, Caamano, Amalia, Carle, Judy, Gonce, Victoria, Staylor, Kaitlyn, Zhou, Na, Bansal, Shweta, Bhattarai, Manoj, Sharma, Kumar, Debnath, Subrata, Garza, Aliseiya, Velagapudi, Chakradhar, Rovner, Sergio, Almeida, Javier, Casares, Pablo, Stewart-Ray, Verlaine, Almaraz, Rene, Dayrell, Renata, Moncada, Ana, Pulido, Ricardo, Rodriquez, Roxana, Deeb, Wasim, Degoursey, Kathryn, Gloria, Rodel, Greene, Trevor, Miller, Robert, Pereira, Edward, Roura, Miguel, Domingo, Debbie, Dorestin, Sasha, Hodge, William, Jackson, Cathy, Lund, Deborah, Taylor, Katrina, Boren, Kenneth, Cleveland, Brittany, Gaiser, Sandra, Sahani, Mandeep, Aldrich, Logan, Edmerson, Exodu, Limon, Edmond, Valletta, Cole, Vasquez, Patricia, Provenzano, Christopher, Brar, Navkiranjot, Henderson, Heather, Keith, Bellovich, Khai, Qur, Khairullah, Quresh, Makos, Gail, Topf, Joel, Gasko, Sherry, Henschel, Rosemarie, Knapp, Kaitlin, Kozlowski, Teresa, Lafleur, Paula, Varughese, Ashwathy, Xue, Hui, Wu, Patricia, Arechiga, Olga, Darbeau, Shan, Fechter, Michael, Martinez, Stephanie, Hanson, Lenita, Cooper, Nyla, Madera, Areli, Cadorna, Jay, Sheridan, Rita, Sparks, Helen, Eilerman, Bradley, Bodine, Susanne, Eid, Wael, Flora, Rebecca, Avery, Amber, Hardy, Cashmere, Biscoveanu, Mihaela, Nagelberg, Steven, Cummins, Tracey, Rahbari-Oskoui, Frederic, Oommen, Anju, Forghani, Zohreh, Hitchcock, Stacie, Hosein, Darya, Watkins, Diane, Patel, Minesh, Lambert, Anthony, Newman, Elizabeth, Wood, Autumn, Ross, Tammy, Topping, Stephany, Mulhern, Jeffrey, Murphy, Lorna, Vasseur, Ann, Greenwood, Gregory, Hadley, Alexander, Laurienti, Denise, Marshall, Christopher, Mclean, Nichola, Satko, Scott, Caudill, Brandy, Maris, Jacob, Rogers, Janice, Vanhoy, Cindy, Thomas, George, Nakhoul, George, O'Toole, John, Taliercio, Jonathan, Cooperman, Leslie, Markovic, Marina, Tucky, Barbara, Dev, Devasmita, Hasan, Alia, Yalamanchili, Hima, Jain, Namita, Mcneil, Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative
Subjects: chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract: Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)
Published: 2023

26. Relationship Between Serum Indirect Bilirubin Levels and Cardiovascular Events and All-Cause Mortality in Maintenance Hemodialysis Patients

Author: Yu Chen, Peilei Zhao, Weifeng Fan, and Jianying Niu
Subjects: Chemical Health and Safety, Therapeutics and Clinical Risk Management, Pharmacology (medical), General Medicine, General Pharmacology, Toxicology and Pharmaceutics, Safety Research
Abstract: Yu Chen, Peilei Zhao, Weifeng Fan, Jianying Niu Department of Nephrology, Shanghai Fifth Peopleâs Hospital, Fudan University, Shanghai, Peopleâs Republic of ChinaCorrespondence: Jianying Niu, Department of Nephrology, Shanghai Fifth Peopleâs Hospital, Fudan University, 801 Heqing Road, Shanghai, 200240, Peopleâs Republic of China, Tel +86-21-24289516, Fax +86-21-24289690, Email niujianying@fudan.edu.cnPurpose: Unconjugated bilirubin is one of the most endogenous antioxidant substances. Mildly elevated total bilirubin concentrations may protect against cardiovascular disease and total death. However, most studies only focused on the association between serum total bilirubin and the risk of cardiovascular disease and total death. This study aimed to investigate the relationship between serum indirect bilirubin (IBIL) and the cardiovascular events in maintenance hemodialysis patients.Patients and Methods:Â : This retrospective cohort study included 284 maintenance hemodialysis patients. Patients were divided into two groups according to the median IBIL level: high IBIL group (IBIL â¥ 3.0 Î¼mol/L) and low IBIL group (IBIL < 3.0 Î¼mol/L). All demographic and laboratory data were recorded at baseline. The endpoint was cardiovascular events and all-cause mortality.Results: During the median follow-up time of 62 months, 96 patients developed cardiovascular disease. There were 134 deaths. In KaplanâMeier analysis curves, the risk of cardiovascular events in the low IBIL group was significantly higher than high IBIL group (P < 0.001). In multivariate Cox regression analysis, the risk of cardiovascular events in high IBIL group was 0.484 times (95% CI 0.278â 0.844, P = 0.010) the risk in low IBIL group. However, there was no significant association between serum IBIL level and all-cause mortality (P = 0.269).Conclusion: Our findings suggest that lower circulating IBIL levels were associated with the increased risk of cardiovascular events in maintenance hemodialysis patients.Keywords: cardiovascular disease, bilirubin, hemodialysis, retrospective study
Published: 2022

27. Study on coupling between mineral resources exploitation and the mining ecological environment in Shanxi Province

Author: Jianying Niu, Jin-Sheng Zhou, Haodong Lv, and Wenjing Wu
Subjects: Sustainable development, Economics and Econometrics, Index (economics), Index system, business.industry, Ecological environment, Geography, Planning and Development, Environmental resource management, 0211 other engineering and technologies, Socioeconomic development, 02 engineering and technology, 010501 environmental sciences, Management, Monitoring, Policy and Law, 01 natural sciences, Mineral resource classification, Mining industry, Coupling (computer programming), 021108 energy, business, 0105 earth and related environmental sciences
Abstract: Due to rapid socioeconomic development, seeking the coordination of resources exploitation and the ecological environment has become an objective requirement for the healthy and sustainable development of the mining industry. This paper selects 23 indicators with which to construct an evaluation index system for mineral resources exploitation and the mining geological ecological environment of Shanxi Province from 2003 to 2015. It then establishes a development index model, a coupling degree model and a coupling coordination degree model. Using a time-series analysis, the comprehensive development level, coupling status and coupling coordination degree of the two systems are analyzed. The results are threefold. (1) The overall level of mineral resources exploitation improved, but, after 2012, the level dropped significantly. The ecological environment in the mining area has improved as a whole, but, due to the ecological fragility caused by long-term extensive mining and acute treatment, the state of the ecological environment fluctuates greatly. (2) The coupling degree between mineral resources exploitation and the mining ecological environment is stable, and it has been in the antagonistic stage for a long time. Although the degree of coupling coordination has improved, it remains at a low level. (3) Further improvement in the coordination between mining exploitation and the mining ecological environment in Shanxi Province has been restricted due to several indicators with greater weights. Recommendations to be considered by policy makers include insufficient sustainable development concepts, outstanding historical issues and the lack of guarantees for environmental protection funds.
Published: 2021
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28. Bioinformatic investigation for candidate genes and molecular mechanism in the pathogenesis of membranous nephropathy

Author: Xiaojing Zhong, Ying Yu, Lihong Zhang, Jianying Niu, and Peng Li
Subjects: Candidate gene, Microarray, Protein Array Analysis, 030232 urology & nephrology, Complement Membrane Attack Complex, Computational biology, 030204 cardiovascular system & hematology, Glomerulonephritis, Membranous, SOXC Transcription Factors, 03 medical and health sciences, 0302 clinical medicine, Databases, Genetic, microRNA, Humans, Medicine, Gene Regulatory Networks, Protein Interaction Maps, Gene, Transcription factor, Genetic Association Studies, business.industry, Competing endogenous RNA, Gene Expression Profiling, Computational Biology, General Medicine, MicroRNAs, Potassium Channels, Voltage-Gated, Nephrology, Toxicogenomics, business, Function (biology)
Abstract: Aim We aimed to explore the detailed molecular mechanism of immune-associated genes in membranous nephropathy (MN). Methods A microarray dataset (GSE133288) was retrieved from the Gene Expression Omnibus database. Differentially expressed mRNAs (DEMs) in MN vs. control groups were identified, and MN-related DEMs (MN-DEMs) were further verified and screened using the Comparative Toxicogenomics Database (CTD) database. The publicly available database, InnateDB was used to investigate immune genes, and the overlapped genes between MN-DEMs and the immune genes were considered as MN-related immune genes (iDEMs). A protein-protein interaction network (PPI) was constructed based on these iDEMs, followed by function and pathway enrichment analysis. Finally, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) associated with iDEMs were predicted, followed by a lncRNA-miRNA-mRNA (competing endogenous RNAs, ceRNA) network construction. Results A total of 327 DEMs and 48 iDEMs were revealed; a PPI network was constructed with 100 PPI pairs and 37 iDEMs. iDEMs including JUN and FOS were mainly enriched in pathways such as osteoclast differentiation and function including response to immobilization stress, respectively. Based on mRNA-associated miRNA and lncRNA prediction, 30 ceRNA interactions including KCNQ1OT1-miR-204-5p-SRY-Box Transcription Factor 4 (SOX4) were explored. Conclusion mRNAs including FOS and JUN might participate in MN development via response to immobilization stress function and the osteoclast differentiation pathway. The mRNA SOX4 might contribute to MN progression via sponging KCNQ1OT1-miR-204-5p interaction. This article is protected by copyright. All rights reserved.
Published: 2020
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29. Curcumin attenuates angiotensin II‐induced podocyte injury and apoptosis by inhibiting endoplasmic reticulum stress

Author: Qing Wu, Yuan Liu, Jianying Niu, Lilu Ling, Nan Yu, Lin Yang, Yong Gu, and Ying Yu
Subjects: 0301 basic medicine, China, podocyte, Curcumin, Apoptosis, Pharmacology, Endoplasmic Reticulum, Kidney, General Biochemistry, Genetics and Molecular Biology, Podocyte, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Renin–angiotensin system, medicine, CKD, Animals, lcsh:QH301-705.5, Research Articles, Cells, Cultured, TUNEL assay, Podocytes, Endoplasmic reticulum, Angiotensin II, Endoplasmic Reticulum Stress, Oxidative Stress, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), chemistry, 030220 oncology & carcinogenesis, Unfolded protein response, ER stress, Reactive Oxygen Species, Research Article
Abstract: Here, we show that curcumin, an active hydrophobic polyphenolic compound extracted from turmeric, could reverse angiotensin II‐induced podocyte injury and apoptosis in a dose‐dependent manner. We found this protective effect of curcumin to be at least partly achieved by inhibiting endoplasmic reticulum stress. Therefore, curcumin may have potential for future development into a possible treatment for chronic kidney disease., Podocytes are an important component of the glomerular filtration barrier in the kidneys. The dysfunction and apoptosis of podocytes are important factors that can lead to the progression of chronic kidney disease (CKD). In CKD, angiotensin II is continuously elevated in circulation and is considered to have key roles in inducing podocyte injury and apoptosis. Curcumin is a hydrophobic polyphenolic compound extracted from turmeric. Increasing evidence demonstrates that curcumin has a protective effect on the kidneys in CKD. However, the mechanisms mediating this protective effect remain unclear. The aim of this study was to explore whether curcumin could protect against angiotensin II‐induced injury and apoptosis of podocytes. We performed western blotting, immunofluorescence, phalloidin staining, and terminal deoxynucleotidyl transferase nick‐end labeling staining to observe the expression level of podocyte‐specific proteins, apoptosis‐related proteins, and the arrangement of F‐actin. We found that curcumin could reverse angiotensin II‐induced podocyte injury and apoptosis in a dose‐dependent manner. In addition, curcumin dose‐dependently attenuated a pro‐apoptotic pathway, activated by angiotensin II‐induced endoplasmic reticulum stress. Conversely, the protective effects of curcumin were impaired upon addition of tunicamycin, an activator of endoplasmic reticulum stress. Thus, we speculate that curcumin protects against angiotensin II‐induced podocyte injury and apoptosis, at least partly by inhibiting endoplasmic reticulum stress.
Published: 2020

30. Plasma Metabolomics Profiling in Maintenance Hemodialysis Patients Based on Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry

Author: Ping Wen, Jianying Niu, Junwei Yang, and Yu Chen
Subjects: Chromatography, Androsterone glucuronide, Metabolite, Fatty liver, Hippuric acid, medicine.disease, End stage renal disease, chemistry.chemical_compound, Metabolic pathway, Metabolomics, Lysophosphatidylcholine, chemistry, medicine, Research Article
Abstract: Background: Key pathogenetic mechanisms underlying renal disease progression are unaffected by current treatment. Metabolite profiling has significantly contributed to a deeper understanding of the biochemical metabolic networks and pathways in disease, but the biochemical details in maintenance hemodialysis (MHD) patients remain largely undefined. Methods: The metabolic fingerprinting of plasma samples from 19 MHD patients and 12 healthy controls was characterized using liquid chromatography quadrupole time-of-flight mass spectrometry. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to analyze the metabolic data. Results: The plasma metabolite profile distinguished the MHD patients from the healthy controls successfully by using both PCA and OPLS-DA models. Sixty-three metabolites were identified as the key metabolites to discriminate the MHD patients from healthy controls, involving several metabolic pathways (all p < 0.05). An increase in plasma levels of D-glucose, hippuric acid, androsterone glucuronide, indolelactic acid, and a reduction in plasma levels of glycerophosphocholine, serotonin, L-lactic acid, phytosphingosine, and several lysophosphatidylcholine were observed in MHD patients compared to healthy subjects. Metabolomics analysis combined with KEGG pathway enrichment analysis revealed that non-alcoholic fatty liver disease, choline metabolism in cancer, the forkhead box O signaling pathway, and the hypoxia-inducible factor-1 signaling pathway in MHD patients were significantly changed (p < 0.05). Conclusion: The identification of a novel signaling pathway and key metabolite markers in MHD patients provides insights into potential pathogenesis and valuable pharmacological targets for end-stage renal disease.
Published: 2020
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31. Association of Sleep Duration with Physical Performance in Hemodialysis Patients: A Multicenter Cross-Sectional Study

Author: Qiunan Zhan, Junli Zhao, Qi Guo, Jianying Niu, Chen Yu, Wei Ding, Liming Zhang, Hualin Qi, and Xiang Shao
Abstract: Background: Hemodialysis (HD) patients have decreased physical function. Getting enough sleep is important for maintaining physical function. However, the relationship between sleep duration and physical performance in HD patients is unclear. Methods: We conducted a multicenter cross-sectional study at seven HD centers in Shanghai and Suzhou, China. 880 HD patients were enrolled between July 2020 and April 2021. Clinical Characteristics, laboratory indicator, sleep assessment data were collected. Physical performance included balance function, muscle strength, and mobility, which were measured by timed up and go test (TUGT), handgrip, and 4-m walk test, respectively. We divided sleep duration into four groups 8–9 h, ≥9 h. Results: A total of 840 patients had completed data (men 525, women 315, mean age 61.24 years). TUGT in group Conclusion: HD patients with abnormal sleep duration had poorer physical performance. Short and long sleep duration were significantly associated with gait speed.
Published: 2022

32. Empagliflozin Ameliorates Preeclampsia and Reduces Postpartum Susceptibility to Adriamycin in a Mouse Model Induced by Angiotensin Receptor Agonistic Autoantibodies

Author: Ruonan Zhai, Yuan Liu, Jiahao Tong, Ying Yu, Lin Yang, Yong Gu, and Jianying Niu
Subjects: Pharmacology, Pharmacology (medical)
Abstract: Preeclampsia (PE) is the leading cause of maternal and perinatal morbidity and mortality and also is a risk factor for cardiovascular and kidney disease later in life. PE is associated with oversecretion of autoantibodies against angiotensin II type 1 receptor (AT1-AA) by the placenta into the maternal circulation. Here, we sought to determine the therapeutic value of the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (EMPA) in mice with AT1-AA-induced preeclampsia. Pregnant mice were injected with AT1-AA at gestation day (GD) 13 and treated daily with EMPA until GD 19, at which point some of the maternal mice were sacrificed and assessed. The other maternal mice were labored on time and challenged with adriamycin (ADR) at 12 weeks postpartum; their offspring were assessed for fetal outcomes. We showed that EMPA treatment significantly relieved high systolic blood pressure and proteinuria and ameliorated kidney injury in PE mice without affecting fetal outcomes. EMPA also ameliorated podocyte injury and oxidative stress, reduced the expression of SGLT2 and activated the AMPK/SIRT1 signaling pathway in vivo and in vitro. Remarkably, EMPA treatment during pregnancy reduced ADR-induced kidney and podocyte injury postpartum. These findings suggest that EMPA could be a potential pharmacological agent for PE.
Published: 2021

33. Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: A randomized, open-label, parallel-group, noninferiority phase III trial

Author: Bicheng Liu, Nan Chen, Jinghong Zhao, Aiping Yin, Xiongfei Wu, Changying Xing, Gengru Jiang, Junzhou Fu, Mei Wang, Rong Wang, Jianying Niu, Ping Fu, Zhaohui Ni, Fanfan Hou, Jiuyang Zhao, Jing Chen, Yuqing Chen, Wei Shi, Jianghua Chen, Wenge Li, Gang Xu, Ling Zhong, Wenhu Liu, Guohua Ding, Yuichiro Kondo, Changhe Yue, and Changlin Mei
Abstract: This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators.Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.
Published: 2021

34. Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure: A randomized, open-label, parallel-group, non-inferiority Phase III trail

Author: Nan Chen, Changying Xing, Jianying Niu, Bicheng Liu, Junzhou Fu, Jiuyang Zhao, Zhaohui Ni, Mei Wang, Wenhu Liu, Jinghong Zhao, Ling Zhong, Xiongfei Wu, Wenge Li, Yuqing Chen, Wei Shi, Jianghua Chen, Aiping Yin, Ping Fu, Rong Wang, Gengru Jiang, Fanfan Hou, Guohua Ding, Jing Chen, Gang Xu, Yuichiro Kondo, Yuliang Su, and Changlin Mei
Abstract: Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.
Published: 2021

35. Heparanase promotes endothelial-to-mesenchymal transition in diabetic glomerular endothelial cells through mediating ERK signaling

Author: Kaili Chang, Qiyuan Xie, Jianying Niu, Yong Gu, Zhonghua Zhao, Fengxia Li, Qiaojing Qin, and Xueguang Liu
Subjects: Cancer Research, Cellular and Molecular Neuroscience, Immunology, Cell Biology
Abstract: Glomerular endothelial cells (GEnCs) dysfunction occurs at the early stage of diabetic nephropathy (DN). One of its characteristics is endothelial-to-mesenchymal transition (EndMT). Heparanase (HPSE) is the only known mammalian endoglycosidase capable of degrading heparin sulfates and has a prominent role in DN pathogenesis. However, whether HPSE induces EndMT of GEnCs remains unknown. This study aimed to determine the effect and potential mechanism of HPSE on GEnCs phenotype under high-glucose conditions. In the early development of streptozotocin (STZ)-induced diabetic mice, HPSE overexpression was positively correlated with renal injury and the number of GEnCs undergoing EndMT, which was characterized by loss of endothelial marker CD31 and gain of mesenchymal markers including α-SMA and Snail1/2 by double immunofluorescence staining. Bioinformatics analysis revealed a positive correlation between HPSE and ERK. The counts of double positive staining of CD31 and p-ERK1/2 was significantly increased in the glomeruli of STZ-induced diabetic mice compared with sham mice. In cultured GEnCs, high glucose dramatically upregulated the expressions of HPSE and p-ERK1/2, both of which were markedly blocked by HPSE siRNA. Furthermore, recombinant mouse HPSE (rmHPSE) promoted the expressions of mesenchymal markers and p-ERK1/2 in a dosage- and time-dependent manner. U0126, a specific MEK/ERK inhibitor, significantly inhibited either high glucose or rmHPSE-induced EndMT of GEnCs. These data indicate that high glucose induces EndMT of GEnCs at least partially through upregulating HPSE and that HPSE promotes EndMT of GEnCs via activating ERK signaling. This study improves understanding the crucial role of HPSE in DN development and progression.
Published: 2021

36. Klotho/FGF23 and Wnt in SHPT associated with CKD

Author: Qing, Wu, Weifeng, Fan, Xiaojing, Zhong, Lihong, Zhang, Jianying, Niu, and Yong, Gu
Subjects: Original Article, urologic and male genital diseases
Abstract: Objective: Recently, the interaction between Klotho/fibroblast growth factor 23 (FGF-23) axis and Wnt signaling has been recognized to be responsible for chronic kidney disease (CKD)-associated comorbidities, including secondary hyperparathyroidism (SHPT). This study aimed to investigate the molecular mechanism of the interaction between Klotho/FGF23 axis and Wnt. Methods: A SHPT model was successfully established with a high-phosphorus diet plus 5/6 nephrectomy. Cell counting Kit-8 (CCK-8) assay and calcium deposit experiment were applied to detect the proliferation and calcium levels. Quantitative real-time PCR (qRT-PCR), Western blotting and immunofluorescence (IF) were used to determine the expression or location of FGF23, calcification-related factors and β-catenin after lentivirus-mediated Klotho overexpression. Luciferase reporter assay was performed to further validate the transcriptional regulation between microRNA-29a (miR-29a) and Dickkopf-1 (DDK1). Results: We found increased serum biochemical factors including parathyroid hormone (PTH), phosphorus, calcium, enhanced parathyroid calcification, and decreased expressions of Klotho in a rat model of secondary hyperparathyroidism. Moreover, genetic-induced upregulation of Klotho inhibited the proliferation, reduced the calcification and the alkaline phosphatase (ALP) activity, and downregulated Wnt/β-catenin signaling in parathyroid cells. Conclusions: Mechanistically, Klotho suppressed miR-29a expression, led to upregulated expression of Wnt/β-catenin signaling inhibitor DKK1, and finally downregulated the activity of Wnt/β-catenin signaling. These findings suggest a novel molecular mechanism in the pathogenesis of CKD-associated SHPT, which provides a potential therapeutic target in the future.
Published: 2021

37. Epidermal growth factor receptor mimotope alleviates renal fibrosis in murine unilateral ureteral obstruction model

Author: Lin Yang, Jianying Niu, Nan Yu, Yong Gu, Ying Yu, Lilu Ling, and Haoran Yuan
Subjects: 0301 basic medicine, Immunology, Apoptosis, Spleen, Kidney, urologic and male genital diseases, Active immunization, Collagen Type I, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Renal fibrosis, Animals, Immunology and Allergy, Macrophage, Epidermal growth factor receptor, biology, business.industry, Mimotope, Macrophages, Molecular Mimicry, Vaccination, Fibrosis, Actins, Fibronectins, ErbB Receptors, Fibronectin, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, biology.protein, Cancer research, Peptides, business, Ureteral Obstruction, 030215 immunology
Abstract: Macrophages have been recognized as a vital factor that can promote renal fibrosis. Previously we reported that the EGFR mimotope could alleviate the macrophage infiltration in the Sjögren's syndrome-like animal model. In current study, we sought to observe whether the active immunization induced by the EGFR mimotope could ameliorate renal fibrosis in the murine Unilateral Ureteral Obstruction (UUO) model. A series of experiments showed the EGFR mimotope immunization could ameliorate renal fibrosis, reduce the expressions of fibronectin, α-SMA and collagen I and alleviate the infiltrations of F4/80+ macrophages in UUO model. Meanwhile, the EGFR mimotope immunization could inhibit the EGFR downstream signaling. Additionally, the frequency of and F4/80+CD9+/FAS+ macrophages significantly increased in spleen after the EGFR mimotope immunization. These evidence suggested that the EGFR mimotope could alleviate renal fibrosis by both inhibiting EGFR signaling and promoting macrophages apoptosis.
Published: 2019
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38. Revised Equations to Estimate Glomerular Filtration Rate from Serum Creatinine and Cystatin C in China

Author: Yonghua Zou, Xin Du, Jianying Niu, Yong Gu, Yule Nan, Tong Lu, and Min Yang
Subjects: Adult, Male, lcsh:Diseases of the circulatory (Cardiovascular) system, China, medicine.medical_specialty, Mean squared error, Serum cystatin C, 030232 urology & nephrology, Urology, Renal function, lcsh:RC870-923, urologic and male genital diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Interquartile range, Chronic kidney disease, lcsh:Dermatology, medicine, Humans, Estimated glomerular filtration rate, Prospective Studies, Cystatin C, Aged, Mathematics, Creatinine, biology, External validation, Reproducibility of Results, General Medicine, lcsh:RL1-803, Models, Theoretical, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, female genital diseases and pregnancy complications, Data Accuracy, Serum creatinine, chemistry, lcsh:RC666-701, Nephrology, biology.protein, Female, Cardiology and Cardiovascular Medicine, Glomerular Filtration Rate, Kidney disease
Abstract: Aim: Our previous study demonstrated that the cystatin C-based chronic kidney disease (CKD)-EPI equation and combined by serum creatinine (CKD-EPIscr-cys) had better capability to accurately evaluate glomerular filtration rate in the CKD participants. Considering that the accuracy of estimated glomerular filtration rate (eGFR) remains less ideally, it is essential to modify the equation by including the Chinese eGFR racial factor in order to improve its performance. Methods: Two prospective cohorts were enrolled in 2 medical centers. New equations were developed in 529 participants and validated in 313 participants. Reference glomerular filtration rate (rGFR) was taken by 99mTc-DTPA renal dynamic imaging method (Gates method). The primary outcomes of this study were bias, precision (interquartile range of difference [IQR]), and accuracy (the proportion of eGFR within 30% of rGFR [P30] and root mean square error [RMSE]) of eGFR versus rGFR. Results: In a development data set, Chinese coefficients for CKD-EPIscr (C-CKD-EPIscr), CKD-EPIcys (C-CKD-EPIcys), and CKD-EPIscr-cys (C-CKD-EPIscr-cys) were 0.871, 0.879, and 0.891, respectively. In a validation data set, C-CKD-EPIcys was the most accurate with highest P30 value (62.3%), relative lowest IQR (15.45), and RMSE (0.80) among 6 equations, though the bias of C-CKD-EPIcys was not better than CKD-EPIcys. C-CKD-EPIscr and C-CKD-EPIscr-cys equations were improved in bias (p < 0.001), precision, and accuracy (p = 0.004 and Conclusion: C-CKD-EPIcys was the most accurate with the highest P30 value, relative lowest IQR, and RMSE among 6 equations. C-CKD-EPIscr and C-CKD-EPIscr-cys equations were improved in bias, precision, and accuracy. Other external validation of these equations is needed.
Published: 2019
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39. Undernutrition when young and the risk of poor renal function in adulthood in women with diabetes in Shanghai, China

Author: Weifeng Fan, Qing Wu, Jianying Niu, Yong Gu, Qiaojing Qin, Xueguang Liu, and Kaili Chang
Subjects: Adult, Medicine (General), Pediatrics, medicine.medical_specialty, China, Adolescent, Renal function, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Biochemistry, 03 medical and health sciences, young adulthood, Young Adult, R5-920, 0302 clinical medicine, Pregnancy, Diabetes mellitus, Medicine, Humans, Shanghai china, Young adult, Child, business.industry, Biochemistry (medical), renal function, Malnutrition, Infant, Newborn, Infant, Undernutrition, Cell Biology, General Medicine, medicine.disease, Starvation, Child, Preschool, Prenatal Exposure Delayed Effects, woman, diabetes mellitus, Famine, famine, Female, business, Retrospective Clinical Research Report
Abstract: Objective To evaluate the effect of undernutrition when young on the risk of poor renal function in adulthood in women with diabetes mellitus. Methods We studied diabetic women born between 1921 and 1958 who were exposed to the 1959-to-1962 Chinese famine when they were 0 to 37 years old. Exposure age was classified as young adulthood (18 to 37 years), adolescence (10 to 17 years), or childhood (0 to 9 years). The Adolescence group, which was provided with the largest amount of food during the famine, was used as the control group, and variance and binary logistic regression analyses were performed. Results The prevalences of low estimated glomerular filtration rate (eGFR) in the Childhood, Adolescence, and Young adulthood groups were 5.26%, 22.39%, and 79.24%, respectively. The risk of low eGFR for the Young adulthood group (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.10, 2.48), but not for the Childhood group (OR 1.10, 95% CI 0.68, 1.78), was higher than that for the Adolescence group after adjustment for potential confounders. Conclusions Undernutrition during young adulthood significantly increases the risk of renal dysfunction in adult women with diabetes. Therefore, the nutrition of less affluent young women should be improved.
Published: 2021

40. Lower serum bilirubin is a risk factor for cardiovascular mortality in maintenance hemodialysis patients: a retrospective cohort study

Author: Jianying Niu, Peilei Zhao, Weifeng Fan, Hongmei Li, Yu Chen, and Xiaojing Zhong
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Medicine, Retrospective cohort study, Maintenance hemodialysis, Risk factor, business, Serum bilirubin, Cardiovascular mortality
Abstract: Background: Although recent studies showed serum bilirubin, an endogenous antioxidant, is protective against cardiovascular diseases, cancer, and diabetic complications, less information is available its association with cardiovascular mortality in hemodialysis patients. This study aimed to investigate the relationship between serum bilirubin and the cardiovascular mortality in maintenance hemodialysis patients.Methods: This retrospective study included 284 chronic hemodialysis patients who started hemodialysis between January 01, 2003, and May 30, 2019. The endpoint was cardiovascular death and all-cause death. A Cox proportional hazards model was used to evaluate the risk factors for cardiovascular death in the maintenance hemodialysis. The cardiovascular mortality was evaluated by Kaplan-Meier analysis.Results: Up to 2019, the median follow-up time was 53 months. In Kaplan–Meier analysis curves, the risk of cardiovascular death in the patients with serum indirect bilirubin (IBIL) levels＜3.0 μmol/L was significantly higher than those with serum IBIL levels≥3.0 μmol/L(p =0.045). In multivariate Cox regression analysis, the risk of cardiovascular mortality in patients with serum IBIL levels ≥3.0 μmol/L was 0.556 times the risk in patients with serum IBIL levels＜3.0 μmol/L (Hazard ratio=0.556, 95% confidence interval 0.334~0.926, p =0.024). However, there was no significant association between serum IBIL and all-cause mortality (p =0.269). Conclusions: Our findings suggest that low serum IBIL level is independently associated with high risk of cardiovascular death in maintenance hemodialysis patients.
Published: 2021
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41. The Study on Serum Urate acid Target for Retarding Renal function to Worse in Diabetes

Author: Heyuan Ding, Yingjun Qian, Qing Wu, Weifeng Fan, Jianying Niu, Yong Gu, and Qiaojing Qin
Abstract: Background: It’s unclear the exact level of serum urate acid (SUA) which can prevent renal function worse although all internists has been known the target of blood glucose, blood pressure and lipid in diabetes. It’s time to aim for a reasonable SUA target to prevent renal failure in diabetes.Methods: Using the physical examination results of 3427 diabetic patients in Jiangchuan Community, Shanghai, China, the relationship between SUA and estimated glomerular filtration rate (eGFR) decline was analyzed, and the appropriate cut-off point for SUA to predict eGFR decline was determined. Meanwhile, the population attributable risk proportion (PARP) of eGFR decline in diabetic patients above this SUA cut-off point was calculated. Results: eGFR decreased accompany with the increased SUA level and was negatively associated with the level of SUA significantly. After adjusting for potential confounders, SUA also was an independent risk factor of eGFR decline. The best appropriate SUA point, predicting eGFR decline obtained by ROC curve, was 326.5μmol/L which may prevent from eGFR decline in 33% male patients and 355.5μmol/L which may prevent from eGFR decline in 18% female patients. Compared with SUA>326.5μmol/L male and SUA>355.5μmol/L female group respectively, the relative risk of eGFR decline in SUA≤326.5μmol/L male and SUA≤355.5μmol/L female group is decreased significantly. Conclusions: SUA is an impotant risk factor for eGFR decline in diabetes. 326.5μmol/L in male and 355.5μmol/L in female may be used as the reasonable SUA target to retard renal function to worse in Chinese diabetes.
Published: 2020
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42. P0890EFFICACY AND SAFETY OF CINACALCET IN CHINESE MAINTENANCE HEMODIALYSIS PATIENTS WITH DIFFERENT STAGES OF SECONDARY HYPERPARATHYROIDISM: INTERIM ANALYSIS RESULTS OF ACTIVE STUDY

Author: Liu Zhi-hong, Jianying Niu, Hong Liu, Jing Chen, Aili Jiang, Xiaonong Chen, Zhangsuo Liu, Ji-Zhuang Lou, Yonghui Mao, Qiang He, Li Hao, Ai-Hua Zhang, Shixiang Wang, Zhaohui Ni, Jun-Wei Yang, Chaosheng Chen, Yisheng Ling, Xuemei Li, Guanqing Xiao, Li Zuo, Ping Fu, Hui Jin, Jian-ming Ye, Yunyan Zhang, and Guohua Ding
Subjects: Transplantation, medicine.medical_specialty, Cinacalcet, business.industry, Maintenance hemodialysis, Active Study, medicine.disease, Interim analysis, Nephrology, Internal medicine, medicine, Secondary hyperparathyroidism, business, medicine.drug
Abstract: Background and Aims Chronic kidney disease (CKD) is a major public health issue worldwide including in China. One of the most common complication in advanced Chronic kidney disease (CKD) is secondary hyperparathyroidism (SHPT). Reports show higher risk of bone fracture, cardiovascular events and all-cause mortality is associated with uncontrolled SHPT in patients with CKD. Cinacalcet, a calcimimetic agent was reported to reduce iPTH levels without Ca increase in patients with SHPT previously. However there has been no large-cohort study and stratified analysis of cinacalcet based on the level of iPTH in China. Moreover, the optimal therapeutic doses of cinacalcet with mild-to-severe SHPT is remaining unknown. ACTIVE study is an IV, open-label, multicenter clinical trial aimed to: (1) evaluate the efficacy and safety of cinacalcet in maintenance hemodialysis patients with mild-to-severe SHPT; (2) explore optimal combinations therapy with cinacalcet and other agents for treating patients with CKD-mineral and bone disorder. (3) investigate the benefit of long-term, continuous medication with cinacalcet in the real-world setting. Method The study design was reported on 2019 ASN. Key inclusion criteria were a baseline iPTH ≥300 pg/mL with life expectancy of ≥2 years, and ≥12 weeks of maintenance dialysis (three dialysis sessions per week) prior to enrollment. The enrollments were grouped based on their iPTH level as having mild (300-600 pg/mL), moderate (600-900 pg/mL) or severe (≥900 pg/mL). Patients initiated treatment with cinacalcet orally at a starting dose of 25 mg once daily (qd). The primary efficacy endpoint is the proportion of patients achieving iPTH targets (iPTH between 150-300pg/mL) at 20 and 32 weeks after the initiation of cinacalcet treatment. Adverse events and serious adverse events were recorded. An interim analysis was scheduled as 375 patients completed 32 weeks visit. Results 911 patients were recruited and of 750 eligible patients, 275 were identified as mild, 224 were considered as moderate and left 251 were grouped as severe SHPT. The study flowchart of 375 patients including mild(127), moderate(106) and severe(142) SHPT for interim analysis was shown in Fig 1. The baseline results including demographic and biomarkers level were reported on 2019 ASN. After 4 weeks’ cinacalcet treatment, serum PTH decreased in all three group, while extremely remarkable in the severe SHPT group. Interim analysis results revealed that the proportion of patients achieving iPTH target (150-300 pg/mL) at 20 wk visit among mild, moderate and severe groups were 38.61% (39/101), 30.11% (28/93) and 10.91% (12/110) respectively. The proportion of patients achieving iPTH target at 32 wk visit in 3 groups increased to 44.68% (42/94), 27.27% (24/88) and 14.56% (15/103) respectively (Table.1). The trends of the proportion of patients achieving iPTH target increased in all 3 different groups (Fig.2). The safety analysis showed the most common treatment-related AE in top 3 including hypocalcemia, hyperlipidemia, and loss of appetite. In vital signs, electrocardiogram (ECG) and laboratory examination of descriptive analysis, found no obvious safety tips. This study is sponsored by Kyowa Hakko Kirin (China) Pharmaceutical Co., Ltd. The analysis is still ongoing and results will be released at EDTA meeting this year. Conclusion Oral cinacalcet HCl was effective and safe in reducing iPTH in patients receiving HD with mild-to-severe SHPT.
Published: 2020
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43. Angiotensin II Type I Receptor Agonistic Autoantibody Induces Podocyte Injury via Activation of the TRPC6- Calcium/Calcineurin Pathway in Pre-Eclampsia

Author: Qian Li, Guang Xu, Lihong Zhang, Yong Gu, Zhenghong Wu, Jianying Niu, and Ying Yu
Subjects: Adult, 0301 basic medicine, lcsh:Diseases of the circulatory (Cardiovascular) system, Calcineurin Pathway, Podocyte, TRPC6, 030204 cardiovascular system & hematology, lcsh:RC870-923, Receptor, Angiotensin, Type 1, Nephrin, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Calcium/calcineurin, TRPC6 Cation Channel, medicine, lcsh:Dermatology, Humans, Cells, Cultured, Autoantibodies, biology, Podocytes, Chemistry, Calcineurin, General Medicine, lcsh:RL1-803, lcsh:Diseases of the genitourinary system. Urology, Angiotensin II, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Nephrology, lcsh:RC666-701, Podocin, biology.protein, Calcium, Female, Synaptopodin, Angiotensin II type I receptor agonistic autoantibody /AT1-AA, Cardiology and Cardiovascular Medicine, Pre-eclampsia, Metabolic Networks and Pathways
Abstract: Background/Aims: Angiotensin II type I receptor agonistic autoantibody (AT1-AA) is closely related to pre-eclampsia, which is characterized by proteinuria and hypertension. AT1-AA has been shown to enhance the effect of AngII in pre-eclampsia, such as production of endothelin-1, activation of ROS, and vasoconstriction, which are considered to be associated with hypertension; however, whether or not AT1-AA participates in podocyte damage leading to the generation of proteinuria has not been reported. In this study we investigated the role of pre-eclamptic serum AT1-AA on podocytes and the mechanism underlying the generation of proteinuria. Methods: The levels of AT1-AA isolated from pre-eclamptic sera were determined by an enzyme-linked immunosorbent assay. Human podocytes were cultured in vitro and treated with various concentrations of AT1-AA. Whether or not an ERK1/2 inhibitor and TRPC6 siRNA inhibit the effect of AT1-AA on podocytes was determined. Western blot was used to detect the expression of podocyte-specific proteins (nephrin, synaptopodin, and podocin) and the phosphorylation of ERK1/2 and TRPC6. The arrangement of F-actin was observed by immunofluorescence. A Calcineurin Cellular Activity Assay Kit was used to detect calcineurin activity. Changes in the intracellular Ca2+ concentration was determined by confocal laser. Results: AT1-AA induced a decrease in podocyte-specific protein expression and calcineurin activity and increased expression of p-ERK1/2 and TRPC6 protein and the intracellular Ca2+ concentration. Immunofluorescence revealed rearrangement of F-actin. PD98059, an inhibitor of ERK1/2, and TRPC6 siRNA attenuated the decreased expression of podocyte-specific proteins and decreased intracellular Ca2+ concentration. The expression of TRPC6 was reduced following the addition of ERK1/2 inhibitor. Conclusion: AT1-AA induced podocyte damage in a dose-dependent manner. The underlying mechanism might involve activation of the TRPC6 –calcium/calcineurin pathway. This study provides new details regarding podocyte injury and the mechanism underlying the generation of proteinuria in pre-eclampsia.
Published: 2018

44. EGFR Mimotope Reduces the Expression of LYVE-1 in the Intestine from the M3R Immunized Mice

Author: Jianying Niu, Lin Yang, Haoran Yuan, and Changhong Li
Subjects: Autoimmune disease, Exocrine gland, biology, 010405 organic chemistry, business.industry, Bioengineering, medicine.disease, 01 natural sciences, Biochemistry, 0104 chemical sciences, Analytical Chemistry, Lymphangiogenesis, medicine.anatomical_structure, Lymphatic system, Immune system, stomatognathic system, Drug Discovery, Lymphatic vessel, medicine, Cancer research, biology.protein, Molecular Medicine, Epidermal growth factor receptor, Receptor, business
Abstract: Primary Sjogren’s syndrome (pSS) is a prototypic autoimmune disease characterized by immune injury to the salivary and lacrimal glands with other systemic manifestations. Recent studies showed the adaptive autoimmune responses induced by muscarinic acetylcholine 3 receptor (M3R) contribute to the dysfunction of exocrine glands in the pathogenesis of pSS. Although the M3R-induced mononuclear cells infiltration are observed in exocrine glands in pSS patients and animal models, the role of M3R in lymphatic vessels formation has not been explored. In current study, we found the expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) increased in intestine of the M3R immunized mice and epidermal growth factor receptor (EGFR) mimotope could inhibit this behavior. Our results suggested that the M3R/EGFR transactivation signaling may help mononuclear cells infiltrate in exocrine glands by promoting lymphangiogenesis.
Published: 2018
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45. Evaluation of the C-domain of heparanase during AGE-induced macrophage inflammatory response

Author: Zhongdong Qiao, Guang Xu, Zhaoxia Wang, Weiwei Qi, Jianying Niu, Mei Guo, Qiaojing Qin, Wangjie Xu, and Yong Gu
Subjects: 0301 basic medicine, Cancer Research, endocrine system, medicine.medical_treatment, Inflammation, macrophage, Biology, Syndecan 1, heparanase, 03 medical and health sciences, Immunology and Microbiology (miscellaneous), medicine, Macrophage, MTT assay, Heparanase, Viability assay, diabetes, advanced glycation end products, syndecan-1, General Medicine, Articles, inflammatory response, Molecular biology, 030104 developmental biology, Cytokine, Tumor necrosis factor alpha, medicine.symptom, hormones, hormone substitutes, and hormone antagonists
Abstract: Diabetic vasculopathy is intensified by macrophage inflammation caused by advanced glycation end products (AGEs). Heparanase (HPA) is a unique endoglycosidase, which cleaves heparan sulfate proteoglycans (HSPGs) including syndecan-1 (Syn-1) to further stimulate macrophage cell migration and inflammation. The present study was planned to evaluated the role of C-domain (if any) of HPA in AGE inflammatory response in macrophages. Cell viability was assessed using MTT assay, migration assay, ELISA for tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, mRNA expression by RT-PCR and heparan degrading enzyme assay for HPA activity. In the present study, we found that pretreatment with anti-HPA antibody, which recognizes the C-domain of HPA inhibited macrophage migration, secretion of IL-1β and TNF-α as well as decreased HPA enzymatic activity and increased Syn-1 protein expression in AGE-induced macrophages. Compared with anti-HPA antibody pretreatment, co-pretreatment with anti-HPA plus Syn-1 antibodies promoted macrophage migration, and secretion of IL-1β and TNF-α significantly in AGE-induced macrophages. In addition, pretreatment with anti-HPA or anti-HPA plus Syn-1 antibodies did not markedly change the mRNA levels of IL-1β and TNF-α concentration AGE-treated macrophages. The results showed that C-domain of HPA mediates AGE-induced macrophage migration and inflammatory cytokine release via Syn-1 protein expression. Furthermore, C-domain of HPA may have a key role in diabetic vascular complication-associated inflammatory response.
Published: 2017

46. Protective Effects of Glucagon-Like Peptide-1 Analog on Renal Tubular Injury in Mice on High-Fat Diet

Author: Min Yang, Bin Wang, Wei Ding, Yong Gu, Lilu Ling, Jianying Niu, Hongmei Li, and Honglei Guo
Subjects: 0301 basic medicine, Male, Physiology, Eukaryotic Initiation Factor-2, Palmitic Acid, Gene Expression, Blood Pressure, Apoptosis, CHOP, AT1R, lcsh:Physiology, Kidney Tubules, Proximal, Eating, Mice, Glucagon-Like Peptide 1, Renal tubular, lcsh:QD415-436, Receptor, Endoplasmic Reticulum Chaperone BiP, Heat-Shock Proteins, Kidney, TUNEL assay, Nephritis, lcsh:QP1-981, Angiotensin II, digestive, oral, and skin physiology, Organ Size, Endoplasmic Reticulum Stress, Glucagon-like peptide-1, medicine.anatomical_structure, ERS, medicine.medical_specialty, Diet, High-Fat, Protective Agents, Receptor, Angiotensin, Type 1, lcsh:Biochemistry, 03 medical and health sciences, In vivo, Internal medicine, medicine, Animals, business.industry, Body Weight, Activating Transcription Factor 4, 030104 developmental biology, Endocrinology, business, GLP-1, Transcription Factor CHOP
Abstract: Aims: The study aimed to investigate the renoprotective effect of glucagon-like peptide-1 (GLP-1) against renal tubular injury in C57BL/6 mice induced by a high-fat diet (HFD). Methods: Twenty C57BL/6 mice were fed HFD for 12 weeks. Ten of these mice were treated with GLP-1 at 200 µg/kg subcutaneously twice daily for 4 weeks (HFDG group), and the other ten mice received vehicle only (HFD group). Ten mice fed standard rodent chow served as controls (Con group). Body weight, kidney weight, food intake, and systolic blood pressure were measured. The expression of endoplasmic reticulum stress (ERS) markers (BIP, p-eIF2α, ATF4, and CHOP) and apoptosis in the kidney were examined utilizing western blotting, immunohistochemistry and TUNEL, respectively. Angiotensin II and angiotensin II type 1 receptor (AT1R) were examined by ELISA. Human proximal tubule epithelial cells (HK2) were treated with GLP-1(150 nM) followed by treatment with palmitic acid (500 nM [PA]) for 24 h. HK2 cells treated with BSA were used as controls. The protein levels of ERS markers, apoptosis-associated protein, and AT1R were measured by western blotting. Results: Increase of body weight, food intake, and systolic blood pressure was less pronounced in GLP-1 treated HFDG mice compared to HFD mice. The levels of ERS markers (BIP, p-eIF2α, ATF4, and CHOP) and apoptosis decreased following GLP-1 treatment in vivo and in vitro (p
Published: 2017

47. Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial

Author: Ruilope, Luis M, Agarwal, Rajiv, Anker, Stefan D, Bakris, George L, Filippatos, Gerasimos, Nowack, Christina, Kolkhof, Peter, Joseph, Amer, Mentenich, Nicole, Pitt, Bertram, Diego, Besada, Alfredo, Wassermann, Julio, Bittar, Alicia, Elbert, Augusto, Vallejos, Gloria, Viñes, Hugo, Sanabria, Federico Pérez Manghi, Alberto, Liberman, Inés, Bartolacci, Diego, Aizenberg, Mariano, Chahin, Laura, Maffei, Elizabeth, Gelersztein, Bernhard, Ludvik, Hans-Robert, Schönherr, Heinz, Drexel, Wolfgang, Preiß, Ursula, Hanusch, Peter, Neudorfer, Friedrich, Prischl, Bernhard, Paulweber, Christoph, Ebenbichler, Rudolf, Prager, Harald, Sourij, Gerit-Holger, Schernthaner, Martin, Clodi, Evelyn, Fliesser-Görzer, Elif, Ekinci, Richard, Macisaac, David, Packham, Hugo, Stephenson, Michael, Suranyi, Gary, Wittert, Katie-Jane, Wynne, Alexia, Pape, Duncan, Topliss, Peter, Colman, Craig, Nelson, James, Vandeleur, David, Colquhoun, Simon, Roger, Peak Mann Mah, Walter, Abhayaratna, Luc VAN Gaal, Pieter, Gillard, Jean-Michel, Hougardy, Marijn, Speeckaert, Koen, Stas, Wendy, Engelen, Francis, Duyck, André, Scheen, Hilde, Vanbelleghem, Peter, Doubel, Svetla, Vasileva, Rosen, Rashkov, Boyan, Nonchev, Theodora, Temelkova-Kurktschieva, Mariana, Yoncheva-Mihaylova, Rangel, Rangelov, Neli, Klyuchkova, Pavel, Stanchev, Zhivko, Tagarev, Radostina, Boshnyashka, Petya, Manova, Zhulieta, Prakova, Mariya, Lucheva, Valentina, Gushterova, Ghassan, Farah, Dimitar, Georgiev, Mariyana, Pichmanova, Dotska, Minkova, Bilyana, Stoyanovska-Elencheva, Maria Eugenia Canziani, Miguel, Hissa, Irene, Noronha, Joao Eduardo Salles, Daniela, Antunes, Freddy, Eliaschewitz, Carlos Eduardo Figueiredo, Rogerio de Paula, Luis, Canani, Maurilo Leite Jr, Bruno, Paolino, Rosangela, Rea, Sergio, Vencio, Claudia, Brito, Raphael, Paschoalin, Roberto Pecoits Filho, Eduardo, Vasconcellos, Nathalia, Paschoalin, Adriana, Forti, Roberto, Botelho, Miguel, Riella, Dalton, Precoma, Maria, Cerqueira, Lilia, Maia, Evandro, Portes, Marcio, Pereira, Joanne, Liutkus, Dennis, O Keefe, Richard, Tytus, Brian, Carlson, James, Conway, Michael, Walsh, Igor, Wilderman, Andrew, Steele, Sheldon, Tobe, Louise, Vitou, Karthik, Tennankore, Valdemar, Martinho, Philip, Mcfarlane, Daniel, Shu, Serge, Cournoyer, Richard, Dumas, Giuseppe, Mazza, Guy, Tellier, George, Tsoukas, Stanley, Weisnagel, Jean-Francois, Yale, Sameh, Fikry, Randolph, Hart, Pavel, Hamet, Francois, Madore, Paul, Barre, Daniel, Schwartz, Allan, Kelly, Ivor, Teitelbaum, Sean, Peterson, Sam, Henein, Richard, Goluch, Gregoire, Wuerzner, Markus, Laimer, Stefan, Bilz, Marc, Donath, Gottfried, Rudofsky, Christopher, Strey, Antoinette, Pechère-Bertschi, Paola, Varleta, Fernando, González, Marcelo, Medina, Carmen, Romero, Victor, Saavedra, Juan Carlos Prieto, Eliana, Reyes, Juan Carlos Palma, Jorge, Cobos, Zhihong, Liu, Dalong, Zhu, Nan, Chen, Fang, Liu, Wang, Li, Qing, Su, Bingyin, Shi, Aiping, Yin, Hao, Wang, Yan, Li, Jianying, Niu, Chaoqing, Wu, Xinjun, Wang, Ying, 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Boonstra, A, C Bakker, R, Marielle, Krekels, B Brouwer, C, T Luik, P, J N, M Barendregt, Bert-Jan van den Born, Trine, Finnes, Thomas, Karlsson, Hilde, Selsås, Emil, Asprusten, Robert, Hagemeier, Erik, Eriksen, Knut, Risberg, Hans, Høivik, Leidulv, Solnør, Frode, Thorup, Jan, Rocke, Rick, Cutfield, Peter, Dunn, Jeremy, Krebs, Russell, Scott, Kingsley, Nirmalaraj, Nine, Smuts, John, Baker, Veronica, Crawford, Albert, Bautista, Roberto, Mirasol, Elizabeth, Catindig, Glenda, Pamugas, Louie, Tirador, Maribel, Tanque, Janusz, Gumprecht, Piotr, Napora, Edward, Franek, Andrzej, Stankiewicz, Katarzyna, Landa, Agnieszka, Tiuryn-Petrulewicz, Kazimierz, Ciechanowski, Bogna, Wierusz-Wysocka, Barbara, Rewerska, Grazyna, Cieslik, Michal, Hoffmann, Michal, Nowicki, Jolanta, Krzykowska, Stanislaw, Mazur, Katarzyna, Wasilewska, Anna, Ocicka-Kozakiewicz, Ewa, Skokowska, Renata, Wnetrzak-Michalska, Jan, Ruxer, Patrycja, Butrymowicz, Katarzyna, Madziarska, Ilona, Kurnatowska, Teresa, Rusicka, Adam, Madrzejewski, Tomasz, Stompor, Jose, Guia, Amalia, Pereira, Pedro, Melo, Cristina, Roque, Francisco, Rosario, Fernando Teixeira, E Costa, Fernando, Nolasco, Edgar, Almeida, Pedro, Matos, Cesar, Esteves, Rui, Carvalho, Ilidio, Brandao, Susana, Heitor, Ana Vila Lobos, Rosa, Ballesteros, Gil, Silva, Carlos, Barreto, Ana, Silva, Natalya, Vorokhobina, Alexander, Sherenkov, Ivan, Gordeev, Olga, Semenova, Sergey, Levashov, Vyacheslav, Marasaev, Ruslan, Sardinov, Vadim, Klimontov, Vitaliy, Baranov, Nadezhda, Verlan, Albert, Galyavich, Arkadiy, Demko, Zhanna, Kobalava, Elena, Zakharova, Lyudmila, Kvitkova, Oleg, Solovev, Elena, Smolyarchuk, Larisa, Zhukova, Elena, Zhdanova, Andrey, Babkin, Galina, Nechaeva, Olga, Barbarash, Elena, Rechkova, Roman, Libis, Elena, Kosmacheva, Tatyana, Rodionova, Irina, Ipatko, Alexander, Dreval, Nina, Petunina, Elena, Chernyavskaya, Alsu, Zalevskaya, Yuriy, Khalimov, Tatyana, Zykova, Anton, Edin, Ashot, Mkrtumyan, Shamil, Palyutin, Vyacheslav, Mareev, Leonid, Strongin, Olga, Ukhanova, Mikhail, Antsiferov, Davyd, Yakhontov, Leonid, Pimenov, Natalya, Koziolova, Konstantin, Nikolaev, Imad, Merai, Olga, Zanozina, Leyla, Gaysina, Mikhail, Arkhipov, Natalia, Malykh, Oksana, Rymar, Vladimir, Martynenko, Sofya, Malyutina, Polina, Ermakova, Marina, Kalashnikova, Bengt-Olov, Tengmark, Carl-Johan, Lindholm, Dan, Curiac, Ken, Eliasson, Erik, Rein-Hedin, Gregor, Guron, Inga, Soveri, Annette, Bruchfeld, Jonas, Spaak, Malin, Frank, Magnus, Löndahl, Hans, Larnefeldt, Margareta, Hellgren, Olof, Hellberg, Yong Mong Bee, Chee Fang Sum, Ru San Tan, Piyamitr, Sritara, Chaicharn, Deerochanawong, Chatlert, Pongchaiyakul, Natapong, Kosachunhanan, Bancha, Satirapoj, Ahmet, Temizhan, Ibrahim, Gul, Ramazan, Sari, Aytekin, Oguz, Mustafa, Tigen, Huseyin, Yilmaz, Ozer, Badak, Oner, Ozdogan, Talat, Tavli, Necmi, Eren, Murat, Cayli, Sedat, Ustundag, Yavuz, Yenicerioglu, Ismail, Kocyigit, Abdulbaki, Kumbasar, Idris, Sahin, Lee-Ming, Chuang, Ju-Ying, Jiang, Chien-Te, Lee, Der-Cherng, Tarng, Shih-Te, Tu, Mai-Szu, Wu, Ming-Ju, Wu, Chiz-Tzung, Chang, Cheng-Chieh, Hung, Liubov, Sokolova, Borys, Mankovsky, Dmytro, Kogut, Viktoriia, Chernikova, Kateryna, Malyar, Nonna, Kravchun, Volodymyr, Botsyurko, Vitaliy, Maslyanko, Liliya, Martynyuk, Oleksandr, Serhiyenko, Vasyl, Stryzhak, Halyna, Myshanych, Oleksandra, Donets, Iryna, Bondarets, Maryna, Vlasenko, Nataliia, Pertseva, Mariia, Grachova, Ivan, Smirnov, Larysa, Pererva, Ivan, Fushtey, Julia, Komisarenko, Anna, Isayeva, Carl, Meisner, Bobby, Khan, Louis, Maletz, Bradley, Dixon, Ahmed, Arif, Timothy, Jackson, Mirela, Ponduchi, Mahfouz El Shahawy, Salil, Nadkarni, Daniel, Urbach, Jorge, Paoli-Bruno, Henry, Lora, Umar, Farooq, Steven, Zeig, Lance, Rudolph, Nabil, Andrawis, William, Kaye, Jill, Meyer, Khalid, Bashir, Glenn, Heigerick, James, Smelser, Javier Ricardo Colomar, David, Scott, Brian, First, Stuart, Handelsman, Jose, Bautista, Rajesh, Patel, Stephen, Minton, Juan, Frias, Luis, Ramos-Gonez, John, Bertsch, Ali, Iranmanesh, Vivian, Fonseca, Michael, Yuryev, Larry, Popeil, Jose, Cardona, Sanjeev, Saxena, Santosh, Sharma, Edgar, Gonzalez, Richard, Solomon, Muhammad, Khan, Ahmed, Awad, David, Fitz-Patrick, Douglas, Linfert, David, Grant, Susan, Brian, Leon, Fogelfeld, Rafael, Canadas, Pablo, Pergola, Joseph, Soufer, Rakesh, Patel, Shujauddin, Valika, Jonathan, Winston, Allison, D, Maria, Caramori, Stanley, Koch, Anjay, Rastogi, Jonathan, Bornfreund, Michael, Rocco, Maxine, Hamilton, Luis, Garcia-Mayol, Peter, Weissman, Suzanne, Oparil, Gary, Ruoff, Kyaw, Soe, Gary, Korff, Robert, Busch, Alexander, Lurie, Israel, Hartman, Garfield, Samuels, Derek, Lejeune, Visal, Numrungroad, Stephen, Brietzke, Zeid, Kayali, Harold, Szerlip, Steven, Barag, Gilberto, Seco, Damaris, Vega, Osvaldo, Brusco, Camil, Kreit, Humberto, Cruz, Bharat, Mocherla, Sharma, Prabhakar, George, Fadda, Martin, Valdes, Eugene, Soroka, Ramin, Berenji, Sreedhara, Alla, Shweta, Bansal, Odugbesan, A, Karlton, Pettis, Masoud, Azizad, Idalia, Acosta, Atoya, Adams, William, Sanchez, Rosa, Suarez, Efrain, Reisin, Carlos, Herrera, Keung, Lee, Csaba, Kovesdy, Adam, Whaley-Connell, Aldo, Peixoto, Ronald, Mayfield, Mahendra, Jain, Earl, Martin, Paul, Norwood, Jonathan, Wise, Hugo, Romeu, Stephen, Halpern, Mustafa, Mandviwala, Thomas, Turk, Anna, Burgner, David, Bleich, Ankur, Doshi, Jose, Carpio, Jorge, Posada, Alexander, Magno, Samer, Nakhle, Gary, Goldstein, Caroline, Mbogua, Dierdre, Mcmullen, Dilawar, Ajani, Wayne, Kotzker, Nelson, Kopyt, Richard, Treger, Yusuf, Ruhullah, Sharon, Adler, Harjeet, Brar, Marc, Rendell, Dennis, Ross, Srinivasan, Beddhu, German, Hernandez, Sylvia, Rosas, M Sue Kirkman, Mohammed, El-Shahawy, Jeffrey, Rothman, Ahmad, Barakzoy, Aparna, Tamirisa, Sabrina, Benjamin, Michael, Bahrami, Prabir, Roy-Chaudhury, Ramprasad, Dandillaya, Gretel, Trullenque, Jose, Birriel, John, Flack, Karen, Johnson, Brenda, Lemus, Guillermo, Umpierrez, Geetha, Maddukuri, Kenneth, Jamerson, Christopher, Case, Patrick, Fluck, Saeed, Kronfli, Violet, Habwe, Bala, Subramanian, Tariq, Shafi, Rupesh, Raina, Roland, Fernando, Sourabh, Kharait, Carlos, Hernandez-Cassis, Raymond, Fink, Jamal, Hammoud, Amer, Al-Karadsheh, Manuel, Montero, Philip, Nicol, Jesus, Navarro, Michael, Shanik, Zia, Din, Francisco, Gonzalez-Abreu, Sam, Lerman, Claude, Galphin, John, Evans, Ashwini, Gore, Radica, Alicic, Mandeep, Sahani, Roberto, Pisoni, Tuan-Huy, Tran, Jeffrey, Ryu, Harvey, Serota, Nilda, Neyra, Richard, O Donovan, Sreedhar, Mandayam, Moustafa, Moustafa, Mark, Smith, Arvind, Krishna, Arjun, Sinha, Anuj, Bhargava, Kodangudi, Ramanathan, Soni, Dhanireddy, Stephen, Thomson, Romanita, Nica, Emaad, Abdel-Rahman, Mark, Barney, Mariana, Markell, Nauman, Shahid, David, Oliver, Tran, Khanh, Pham Nguyen Son, Lam VAN Hoang, Boi Ngoc Nguyen, Nguyen Minh Nui, Lan Phuong Tran, Fayzal, Ahmed, Dorothea, Urbach, Dirkie Jansen van Rensburg, Gracjan, Podgorski, Aslam, Amod, Sindeep, Bhana, Shaifali, Joshi, Essack, Mitha, Deepak, Lakha, Louis van Zyl, Trokis, J, Naresh, Ranjith, Mary, Seeber, Mohamed, Sarvan, Mohammed, Tayob, Brian, Rayner, Larry, Distiller, Heidi, Siebert, Mukesh, Joshi, Paul, Rheeder, Magdalena Madero Rovalo, Gustavo Solache Ortiz, Gustavo Méndez Machado, Rafael Valdez Ortiz, Juan Villagordoa Mesa, Saúl Irizar Santana, Sandro Avila Pardo, Jorge Escobedo de la Peña, Guillermo González Gálvez, Leobardo Sauque Reyna, Miriam Bastidas Adrian, Guillermo Fanghänel Salmón, Ramiro Gutiérrez Ochoa, Luis Nevarez Ruiz, Gabriel Ramos López, Alfredo Chew Wong, Arturo Saldaña Mendoza, Pedro García Hernández, José González González, Melchor Alpizar Salazar, José Lazcano Soto, Amaury, Roman-Miranda, Gregorio, Cortes-Maisonet, Liana, Turcu, Adriana, Dumitrescu, Gabriela, Radulian, Hortensia, Barbonta, Cristina, Mistodie, Georgeta, Vacaru, Alexandrina, Popescu, Adrian, Vlad, Silvia, Paveliu, Nicoleta, Mindrescu, Adrian, Albota, Ella, Pintilei, Lavinia, Pop, Gabriela, Negrisanu, Doina, Catrinoiu, Cornelia, Bala, Amorin, Popa, Iosif, Szilagyi, Ciprian, Constantin, Elena, Caceaune, Adriana, Onaca, Li Yuan Lee, Nor Azizah Aziz, Wan Mohd Izani Wan Mohamed, Wan Hasnul Halimi Bin Wan Hasan, Jeyakantha, Ratnasingam, Nik Nur Fatnoon Nik Ahmad, Rizmy Najme Khir, Norhaliza Mohd Ali, Masni, Mohamad, Chek Loong Loh, Joe, Eustace, John, Holian, Donal, Reddan, Yvonne, O Meara, Mensud, Hatunic, Zuzana, Ochodnicka, Dalibor, Sosovec, Andrej, Dzupina, Ingrid, Buganova, Jana, Babikova, Denisa, Spodniakova, Ruilope, L, Agarwal, R, Anker, S, Bakris, G, Filippatos, G, Nowack, C, Kolkhof, P, Joseph, A, Mentenich, N, Pitt, B, Trevisan, R, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Diabetes Clinic
Subjects: Male, Endocrinology, Diabetes and Metabolism, Enfermedad cardiovascular, 030232 urology & nephrology, BAY 94-8862, Type 2 diabetes, 030204 cardiovascular system & hematology, Diabete, Kidney, Aparato circulatorio, Azúcar, chemistry.chemical_compound, Mineralocorticoid Receptor Antagonists/therapeutic use, 0302 clinical medicine, Medicine and Health Sciences, Diabetic Nephropathies, Myocardial infarction, Renal Insufficiency, Chronic, Aldosterone, Outcome, Mineralocorticoid Receptor Antagonists, RISK, COMPLICATIONS, Diabetes, Middle Aged, SPIRONOLACTONE, CHRONIC HEART-FAILURE, Treatment Outcome, Mineralocorticoid, Nephrology, Cardiovascular Diseases, Research Design, Disease Progression, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Type 2, Glomerular Filtration Rate, medicine.medical_specialty, Finerenone, Naphthyridines/therapeutic use, Renal function, Outcomes, 03 medical and health sciences, Clinical, Double-Blind Method, Diabetes mellitus, Internal medicine, medicine, Diabetes Mellitus, Humans, Naphthyridines, Renal Insufficiency, Chronic, ANTAGONIST, Sistema cardiovascular, Aged, Patient-Oriented, Translational Research: Research Article, Diabetic Nephropathies/complications, Renal Insufficiency, Chronic/drug therapy, RECEPTOR, Aldosterone, Clinical, Diabetes, Kidney, Mineralocorticoid, Outcomes, business.industry, Cardiovascular Diseases/epidemiology, Diabetes Mellitus, Type 2/complications, MILD, WORSENING RENAL-FUNCTION, EFFICACY, medicine.disease, chemistry, Diabetes Mellitus, Type 2, Spironolactone, Albuminuria, business, Kidney disease, Follow-Up Studies
Abstract: Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
Published: 2019
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48. The Chronic Adverse Effect of Chloroquine on Kidney in Rats through an Autophagy Dependent and Independent Pathways

Author: Bin Wang, Yong Gu, Jianying Niu, Lilu Ling, Jialing Ji, and Honglei Guo
Subjects: medicine.medical_specialty, Vasopressin, medicine.drug_class, 030232 urology & nephrology, Renal function, Apoptosis, 030204 cardiovascular system & hematology, Kidney, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Autophagy, Cyclic AMP, Animals, Exosomal secretion, Aquaporin 2, urogenital system, business.industry, Glomerulosclerosis, Chloroquine, medicine.disease, Cyclic AMP-Dependent Protein Kinases, Rats, medicine.anatomical_structure, Endocrinology, Receptors, Mineralocorticoid, Mineralocorticoid, Aquaporin 1, business, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract: Background: Chloroquine (CQ), a classic autophagy inhibitor, is used clinically for malaria prophylaxis and pulmonary hypertension treatment. The adverse effects of CQ on morphological and functional changes in the kidney were investigated in the current study due to CQ accumulation in the kidney. Methods: Twelve male Sprague-Dawley rats were randomly divided into 2 groups for 4 weeks: group 1, control (n = 6); and group 2, CQ administration group (50 mg–1·kg per day ip; n = 6). Serum aldosterone and vasopressin were measured by radioimmunoassay. Immunofluorescence was used to colocalize Tunel with aquaporin 1, aquaporin 2 (AQP2), and Tamm-Horsfall protein. Expression of AQP2 and mineralocorticoid (MR) was detected by western blot and immunohistochemistry. Results: In the present study, 4 weeks of CQ administration were shown to induce severe kidney injury, including glomerular sclerosis and tubular cells apoptosis, especially distal tubular cells. Decreased expression of LC3II/I and p-AKT was demonstrated in CQ-treated rats. Glomerular and proximal tubule injury were associated with impaired autophagy flux, and distal tubule injury may be associated with downregulated cyclic adenosine monophosphate (cAMP)/PKA/AKT signaling. Both MR and AQP2, which are mainly located in the distal tubule and collecting duct, were significantly reduced in CQ-treated rats, thus leading to increased exosomal secretion of AQP2 in urine. Additionally, chronic CQ administration increased aldosterone and vasopressin levels in serum, but lowered the blood pressure, glomerular filtration rate, and urine concentration. Conclusions: CQ administration damages glomerular, proximal tubule autophagy, and severe distal tubular cells apoptosis by inhibiting cAMP/PKA/AKT signaling.
Published: 2019

49. A Telemedicine-Based Registration System for the Management of Renal Anemia in Patients on Maintenance Hemodialysis: Multicenter Study

Author: Chen Yu, Yi Wang, Junli Zhao, Gengru Jiang, Zhaohui Ni, Qing Yu, Kun Liu, Liming Zhang, Xiuzhi Yu, Shougang Zhuang, Haijiao Jin, Jun Ma, Chun Hu, Junli Zhang, Jianying Niu, Yueyi Deng, Huimin Jin, Shoujun Bai, Ai Peng, Xiaoxia Wang, Xudong Xu, Rong Zhou, Qin Wang, Ying Li, Xiaorong Bao, Xiujuan Zang, Zhiyong Guo, Jianrao Lu, and Niansong Wang
Subjects: Male, medicine.medical_specialty, Anemia, medicine.medical_treatment, Health Informatics, Telehealth, Hematocrit, End stage renal disease, chemistry.chemical_compound, dialysis registration system, Renal Dialysis, Internal medicine, medicine, Humans, Dialysis, Creatinine, Original Paper, hemodialysis, end-stage renal disease, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, Telemedicine, chemistry, Chronic Disease, Kidney Failure, Chronic, Female, Hemodialysis, Hemoglobin, business, renal anemia
Abstract: Background: Renal anemia is one of the most important complications in patients on maintenance hemodialysis (MHD). Telehealth-based dialysis registration systems have the advantage of real-time monitoring and have gradually been applied to the management of chronic diseases. Objective: The objective of our study was to evaluate the impact of a telehealth-based dialysis registration system on patients on MHD in terms of renal anemia control. Methods: The Red China project aimed to develop a dialysis registration system based on the WeChat mobile platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, and baseline creatinine levels were recorded using this system. In addition, the hemoglobin and hematocrit levels were recorded monthly. The platform then generated a hemoglobin and hematocrit statistics report for each hemodialysis center monthly, including the detection rate, target rate, and distribution of hemoglobin and released it to physicians via the WeChat mobile phone app. The physicians were then able to treat the individual’s anemia appropriately by changing the doses of erythropoiesis-stimulating agents or iron use on the basis of this report. We analyzed the demographic and baseline laboratory parameters, detection rate, target rate, and average level and distribution of hemoglobin 28 months after the launch of the project. Results: A total of 8392 patients on MHD from 28 hemodialysis centers in Shanghai were enrolled from June 2015 to October 2017. The detection rate of hemoglobin increased from 54.18% to 73.61% (P
Published: 2019

50. The Correlation between Serum Uric Acid and Renal Function in Elderly Chinese Diabetes with Normoalbuminuria

Author: Yong Gu, Ying-jun Qian, Guanghua Zhu, Jianying Niu, Weifeng Fan, and Qiaojing Qin
Subjects: medicine.medical_specialty, Article Subject, Endocrinology, Diabetes and Metabolism, 030232 urology & nephrology, Blood lipids, Renal function, 030209 endocrinology & metabolism, Urine, Gastroenterology, lcsh:Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, medicine, Hyperuricemia, Creatinine, lcsh:RC648-665, Endocrine and Autonomic Systems, business.industry, medicine.disease, Blood pressure, chemistry, Hemoglobin, business, Research Article
Abstract: Objective. The elder diabetic patients increases rapidly in China and often accompany with hyperuricemia. Recently evidences show that renal function has been impaired in part of diabetic patients with normoalbuminuria. Therefore, we investigated the relationship between serum uric acid (SUA) and renal function in Chinese elder diabetes with normoalbuminuria. Methods. The physical examination data from 1052 cases of diabetic residents with normoalbuminuria aged 70 years and over in the Jiangchuan community of Minhang District, Shanghai, from October 2011 to September 2014 was analyzed retrospectively. Each received height, body weight, waist circumference (WC), waist-to-hip ratio (WHR), blood pressure (BP), and collected samples of fasting blood and morning urine to detect blood routine, blood glucose, glycosylated hemoglobin (HbA1c), blood lipids, serum creatinine, urinary albumin, urine creatinine, and urine PH value. Correlation between SUA and renal function, an index of which is estimated using estimated glomerular filtration rate (eGFR), was analyzed. Results. The prevalence of hyperuricemia was 21.10%. Levels of WC and triglyceride (TG) increased and the levels of HbA1c, high density lipoprotein-cholesterol (HDL-C), eGFR, and urine PH decreased while the levels of SUA increased. Moreover, negative correlation of eGFR with age, WC, leukocyte, and SUA (Pearson r=0.415) was observed via Pearson correlation analysis. It indicates the strong association between SUA and eGFR. Furthermore, eGFR independently associated with SUA, age, leukocyte, hemoglobin (Hb), and fasting blood glucose (FBG) was confirmed by multiple linear stepwise regression analysis. Conclusion. SUA may play an important role in the decrease of eGFR in elderly Chinese diabetic patients with normoalbuminuria.
Published: 2019

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