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The role of NADPH oxidase (Nox)-derived reactive oxygen species in kidney vascular function has extensively been investigated in the harmful context of oxidative stress in diabetes and obesity-associated kidney disease. Since hydrogen peroxide (H2O2) has recently been involved in the non-nitric oxide (NO) non-prostanoid relaxations of intrarenal arteries, the present study was sought to investigate whether NADPH oxidases may be functional sources of vasodilator H2O2 in the kidney and to assess their role in the endothelium-dependent relaxations of human and rat intrarenal arteries. Renal interlobar arteries isolated from the kidney of renal tumor patients who underwent nephrectomy, and from the kidney of Wistar rats, were mounted in microvascular myographs to assess function. Superoxide (O2.-) and H2O2 production was measured by chemiluminescence and Amplex Red fluorescence, and Nox2 and Nox4 enzymes were detected by Western blotting and by double inmunolabeling along with eNOS. Nox2 and Nox4 proteins were expressed in the endothelium of renal arterioles and glomeruli co-localized with eNOS, levels of expression of both enzymes being higher in the cortex than in isolated arteries. Pharmacological inhibition of Nox with apocynin and of CYP 2C epoxygenases with sulfaphenazol, but not of the NO synthase (NOS), reduced renal NADPH-stimulated O2.- and H2O2 production. Under conditions of cyclooxygenase and NOS blockade, acetylcholine induced endothelium-dependent relaxations that were blunted by the non-selective Nox inhibitor apocynin and by the Nox2 or the Nox1/4 inhibitors gp91ds-tat and GKT136901, respectively. Acetylcholine stimulated H2O2 production that was reduced by gp91ds-tat and by GKT136901. These results suggest the specific involvement of Nox4 and Nox2 subunits as physiologically relevant endothelial sources of H2O2 generation that contribute to the endothelium-dependent vasodilatation of renal arteries and therefore have a protective role in kidney vasculature., Graphical abstract fx1

Aims To describe how people diagnosed with chronic kidney disease and their family members describe uncertainty related to impending death. Background There has been little research about the experiences of people with chronic kidney disease and their family members as they near the end-of-life. We need to understand these experiences to give holistic person-centred care. Design A narrative enquiry was undertaken using a social constructionist perspective. Methods Data were collected in two in-depth interviews, approximately 3-4 months apart, followed by a telephone follow-up 2-3 months later. Results Eleven people with advanced chronic kidney disease and nine family members/significant others participated. For both participants in the dyad, a number of key themes/storylines were identified. These included recognition that: @life has a boundary, living on the edge, I'm not afraid to die but… and remembering loss and death experiences@. Conclusions This enquiry illuminated four key storylines of about death and dying with advanced chronic kidney disease for people with the illness and their family members. Discussion about past experiences with illness, loss, death, and dying can give an entry for discussion about end-of-life. The person with illness and family members often held very similar perceptions and desires, but healthcare professionals' contributions to understanding of the experience were not mentioned. Implications for clinicians include attending to peoples' awareness of death as a distinct opportunity, listening attentively and posing questions that genuinely invite concerns and wishes about end-of-life and living well.

Background: Oxidative stress and inflammation are proposed mechanisms of nonspecific kidney injury and progressive kidney failure. Higher dietary oxidative balance scores (OBS) are associated with lower prevalence of chronic kidney disease (CKD). Methods: We investigated the association between OBS and biomarkers of inflammation using data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Nutrient estimates from the Block Food Frequency Questionnaires were used to define tertiles of 11 pro- and antioxidant factors. Points for each OBS component were summed, with a higher score indicating predominance of antioxidant exposures. Multivariable linear regression models were used to estimate the association between OBS and biomarkers of inflammation (interleukin-6 [IL-6], interleukin-8 [IL-8], interleukin-10 [IL-10], fibrinogen, C-reactive protein [CRP], white blood cell count, and cystatin C). An interaction term was included to determine if associations between OBS and inflammatory markers differed between individuals with and without CKD. Results: Of 682 participants, 22.4% had CKD. In adjusted models, OBS was associated with CRP and IL-6. For every 5-unit increase in OBS, the CRP concentration was –15.3% lower (95% CI: –25.6, –3.6). The association of OBS with IL-6 differed by CKD status; for every 5-unit increase in OBS, IL-6 was –10.7% lower (95% CI: –16.3, –4.7) among those without CKD, but there was no association among those with CKD (p = 0.03). Conclusion: This study suggests that a higher OBS is associated with more favorable levels of IL-6 and CRP, and that the association of OBS and IL-6 may be modified by CKD status.

// Yu-Jih Su 1 , I-Chun Lin 2 , Lin Wang 3 , Cheng-Hsien Lu 4,5,6 , Yi-Ling Huang 1 and Ho-Chang Kuo 7 1 Department of Rheumatology, Allergy and Immunology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Pediatrics, PoJen Hospital, Kaohsiung, Taiwan 4 Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan 6 Department of Neurology, Xiamen Chang Gung Memorial Hospital, Xiamen, Fujian, China 7 Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Correspondence to: Ho-Chang Kuo, email: erickuo48@yahoo.com.tw Keywords : next generation sequencing; lupus; nephritis; microRNA; Immunology Received: October 29, 2017 Accepted: May 08, 2018 Published: June 15, 2018 Abstract The symptomatology of lupus nephritis (LN) consists of foamy urine and lower leg edema, as well as such systemic manifestations as oral ulcers, arthralgia/arthritis, and lymphadenopathy. However, these symptoms may appear mild and non-specific. If these symptoms are unrecognized, thus delaying treatment, approximately 10% of LN patients will develop permanent kidney damage and end-stage kidney disease. Therefore, the purpose of this study is to identify a surrogate biomarker for the early detection of LN. In this study, we first adopted next generation sequencing (NGS) in order to screen differential expression levels of microRNA between SLE patients with and without LN. The results of both the NGS and the literature review confirmed the potential of 15 microRNAs through real-time qPCR. We further considered clinical laboratory data for additional analysis. In total, 41 microRNAs demonstrated significant differences through NGS screening. We then verified eight microRNAs from NGS and seven microRNAs from the literature review using the real-time qPCR method in peripheral mononuclear cells. Ultimately, mir-125a-5p, miR-146a-5p, and mir-221-3p were found to be statistically significant not only in the screening study but also in the real-time qPCR verification studies. miR-146a-5p was observed to have a significant correlation with clinical biochemistry markers, as well as to be a surrogate biomarker for the early detection of lupus nephritis. This study is the first to show that the intracellular biomarker miR-146a-5p may serve as a useful specific biomarker for the detection of lupus nephritis among lupus patients in the future, regardless of serum albumin levels and spot urine protein/creatinine ratio.

// Hideo Yuki 1, * , Takao Kamai 1, * , Satoshi Murakami 1, 2 , Satoru Higashi 3 , Takahiro Narimatsu 1 , Tsunehito Kambara 1 , Hironori Betsunoh 1 , Hideyuki Abe 1 , Kyoko Arai 1 , Hiromichi Shirataki 3 and Ken-Ichiro Yoshida 1 1 Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan 2 Division of Field Application, Life Technologies, Tokyo, Japan 3 Department of Molecular and Cell Biology, Dokkyo Medical University, Mibu, Tochigi, Japan * These authors have contributed equally to this work Correspondence to: Takao Kamai, email: kamait@dokkyomed.ac.jp Keywords: nuclear factor erythroid 2–related factor 2 (Nrf2); chronic kidney disease (CKD); renal cell cancer Received: December 04, 2017 Accepted: April 17, 2018 Published: June 19, 2018 ABSTRACT Chronic kidney disease (CKD) is a worldwide health problem, and prevention of CKD is important for preservation of renal function after kidney surgery. There is evidence that transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) has a vital antioxidant and detoxifying role in protecting the kidneys against various diseases. Impaired activation of Nrf2 is associated with oxidative stress related to CKD, and Nrf2 is also a key player in the development of cancer. However, the clinical impact of Nrf2 has not been investigated in patients with renal cell carcinoma (RCC). A retrospective study was performed in 89 patients undergoing nephrectomy for RCC. The estimated glomerular filtration rate (eGFR) and serum uric acid (SUA) were investigated over time after surgery. We investigated Nrf2 protein expression in all tumors and single nucleotide polymorphisms (SNPs) of the Nrf2 gene in 7 tumors. In patients whose tumors showed higher Nrf2 expression, there was a more rapid decrease of eGFR and increase of SUA after nephrectomy. Multivariate analysis confirmed that increased Nrf2 expression was an independent poor prognostic factor related to shorter overall survival. Among the 7 tumor samples, an SNP on exon 5 of the Nrf2 gene in one tumor and three genotypes (C/C, C/A, and A/A) of rs6721961 at the promoter region of the Nrf2 gene were observed. Although the mechanisms underlying the influence of Nrf2 are still unclear, our findings suggested that elevated tumor expression of Nrf2 was associated with postoperative CKD and biologically aggressive RCC with an unfavorable prognosis.

BACKGROUND Living kidney donors face the risk of renal dysfunction, resulting in end-stage renal disease, cardiovascular disease, or cerebrovascular disease, after donor nephrectomy. Reducing this risk is important to increasing survival of living donors. In this study, we investigated the effect of preoperative distribution of abdominal adipose tissue and nutritional status on postoperative renal function in living donors. MATERIAL AND METHODS Seventy-five living donors were enrolled in this retrospective study. Preoperative unenhanced computed tomography images were used to measure abdominal adipose tissue parameters. Prognostic nutritional index (PNI) was used to assess preoperative nutritional status. Donors were divided into 2 groups according to abdominal visceral adipose tissue (VAT) area at the level of the fourth and fifth lumbar vertebrae (

// Wen Zhang 1, 2, 3 , Yugen Sha 1, 2, 3 , Ke Wei 1, 2, 3 , Chunfeng Wu 1, 2, 3 , Dan Ding 1, 2, 3 , Yunwen Yang 1, 2, 3 , Chunhua Zhu 1, 2, 3 , Yue Zhang 1, 2, 3 , Guixia Ding 1, 2, 3 , Aihua Zhang 1, 2, 3 , Zhanjun Jia 1, 2, 3 and Songming Huang 1, 2, 3 1 Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing 210008, China 2 Jiangsu Key Laboratory of Pediatrics, Nanjing 210029, China 3 Nanjing Key Laboratory of Pediatrics, Nanjing 210008, China Correspondence to: Songming Huang, email: smhuang@njmu.edu.cn Keywords: rotenone; mitochondria; AKI; CKD Received: December 15, 2017 Accepted: February 25, 2018 Published: May 11, 2018 ABSTRACT Acute kidney injury (AKI) has been widely recognized as an important risk factor leading to the occurrence and progression of chronic kidney disease (CKD). Thus, development of the strategies in retarding the transition of AKI to CKD is becoming a hot research field. Recently, accumulating evidence suggested a pathogenic role of mitochondrial dysfunction in both AKI and CKD. Therefore, in the present study, we evaluated the effect of mitochondrial complex 1 inhibition by rotenone on the chronic renal damage induced by acute ischemia-reperfusion. The mice were treated with 45 min unilateral renal ischemia and reperfusion (I/R) to induce an acute renal injury. After three days of I/R injury, rotenone at a dose of 200 ppm in food was administered to the mice. Strikingly, after three weeks treatment with rotenone, we found that the unilateral I/R-induced tubular damage, tubulointerstitial fibrosis were all attenuated by rotenone as determined by the tubular injury score, Masson staining, and the levels of collagen-I, collagen-III, fibronectin, PAI-1, and TGF-β. Meanwhile, the enhanced inflammatory markers of TNF-α, IL-1β, IL-6, and IL-18 and apoptotic markers of Bax and caspase-3 were all significantly blunted by inhibiting mitochondrial complex-1. Moreover, rotenone treatment also partially protected the mitochondria as shown by the restoration of mitochondrial SOD (SOD2), ATPB, and mitochondrial DNA copy number. These findings suggested that inhibition of mitochondrial complex-1 activity by rotenone could retard the progression of AKI to CKD probably via protecting the mitochondrial function to some extent.

Objective This questionnaire-based cross-sectional survey reported the attitudes and practices of Chinese doctors regarding chronic kidney disease (CKD) and acute kidney injury (AKI) management. Methods An online questionnaire consisting of general information, awareness of CKD and AKI, education status, renal laboratory items, and clinical practices between February 20, 2017 and August 15, 2017. Results Among the 1289 respondents from secondary and tertiary hospitals in 30 provinces, 718 (55.7%) were nephrologists, 94.3% had the ability to evaluate glomerular filtration rates, and 98.8% could evaluate urinary protein excretion, indicating that Chinese doctors met the minimum requirements to manage CKD. However, nearly half of all respondents reported that easy methods for spot urine creatinine-adjusted urinary protein assessments were unavailable. Awareness of the CKD risk stratification system and AKI definition was inadequate, and only 54.2% of respondents reported that they had received nutritional education for renal diseases. Although most of the respondents were nephrologists at university hospitals, 66.4% and 76.3% of respondents reported nephrology referrals and nephrology consultations, respectively, after AKI, suggesting an insufficient role for nephrologists. Finally, management models differed significantly, indicating that universal guidelines for CKD and AKI management are required across China. Conclusions Several considerable challenges remain regarding CKD and AKI management in China, including inadequate knowledge and training systems, an absence of clinical protocols, and insufficient multidisciplinary cooperation. Electronic supplementary material The online version of this article (10.1007/s11255-018-1882-1) contains supplementary material, which is available to authorized users.

BACKGROUND As end-stage liver disease progresses, renal blood flow linearly correlates with mean arterial blood pressure (MBP) due to impaired autoregulation. We investigated whether the lower degree of postoperative MBP would predict the occurrence of postoperative acute kidney injury (AKI) after liver transplantation. MATERIAL AND METHODS This retrospective study enrolled 1,136 recipients with normal preoperative kidney function. Patients were categorized into two groups according to the averaged postoperative MBP

Background: Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD). Objective/methods: We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8-week study of 1085 participants with clinic SBP 160–190 mmHg and DBP 119 mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/90 mmHg (≥130/80 mmHg if diabetes or chronic kidney disease). The primary endpoint was change from baseline in clinic SBP; 24-h ambulatory BP monitoring was also measured. Results: Greater reductions in clinic SBP from a baseline of 165 mmHg were observed (P

The retention of uremic toxins and their pathological effects occurs in the advanced phases of chronic kidney disease (CKD), mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment. However, the start of hemodialysis is associated with both an acceleration of the loss of residual kidney function (RKF) and the shift to an increased intake of proteins, which are precursors of uremic toxins. In this phase, hemodialysis treatment is the only way to remove toxins from the body, but it can be largely inefficient in the case of high molecular weight and/or protein-bound molecules. Instead, even very low levels of RKF are crucial for uremic toxins excretion, which in most cases are protein-derived waste products generated by the intestinal microbiota. Protection of RKF can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days. This approach could represent a tailored strategy aimed at limiting the retention of both inorganic and organic toxins. In this paper, we discuss the combination of upstream (i.e., reduced production) and downstream (i.e., increased removal) strategies to reduce the concentration of uremic toxins in patients with ESKD during the transition phase from pure conservative management to full hemodialysis treatment.

Background Chronic kidney disease (CKD) is a common and costly condition that is usually accompanied by multiple comorbidities including type 2 diabetes, hypertension, and obesity. Proper management of CKD can delay or prevent kidney failure and help mitigate cardiovascular disease risk, which increases as kidney function declines. Smart device apps hold potential to enhance patient self-management of chronic conditions including CKD. Objective The objective of this study was to develop a mobile app to facilitate self-management of nondialysis-dependent CKD. Methods Our stakeholder team included 4 patients with stage 3-4 nondialysis-dependent CKD; a kidney transplant recipient; a caretaker; CKD care providers (pharmacists, a nurse, primary care physicians, a nephrologist, and a cardiologist); 2 health services and CKD researchers; a researcher in biomedical informatics, nutrition, and obesity; a system developer; and 2 programmers. Focus groups and in-person interviews with the patients and providers were conducted using a focus group and interview guide based on existing literature on CKD self-management and the mobile app quality criteria from the Mobile App Rating Scale. Qualitative analytic methods including the constant comparative method were used to analyze the focus group and interview data. Results Patients and providers identified and discussed a list of requirements and preferences regarding the content, features, and technical aspects of the mobile app, which are unique for CKD self-management. Requirements and preferences centered along themes of communication between patients and caregivers, partnership in care, self-care activities, adherence to treatment regimens, and self-care self-efficacy. These identified themes informed the features and content of our mobile app. The mobile app user can enter health data including blood pressure, weight, and blood glucose levels. Symptoms and their severity can also be entered, and users are prompted to contact a physician as indicated by the symptom and its severity. Next, mobile app users can select biweekly goals from a set of predetermined goals with the option to enter customized goals. The user can also keep a list of medications and track medication use. Our app includes feedback mechanisms where in-range values for health data are depicted in green and out-of-range values are depicted in red. We ensured that data entered by patients could be downloaded into a user-friendly report, which could be emailed or uploaded to an electronic health record. The mobile app also includes a mechanism that allows either group or individualized video chat meetings with a provider to facilitate either group support, education, or even virtual clinic visits. The CKD app also includes educational material on CKD and its symptoms. Conclusions Patients with CKD and CKD care providers believe that a mobile app can enhance CKD self-management by facilitating patient-provider communication and enabling self-care activities including treatment adherence.

Background COVID-19 became a pandemic rapidly after its emergence in December 2019. It belongs to the coronavirus family of viruses, which have struck a few times before in history. Data based on previous research regarding etiology and epidemiology of other viruses from this family helped played a vital role in formulating prevention and precaution strategies during the initial stages of this pandemic. Data related to COVID-19 in Pakistan were not initially documented on a large scale. In addition, due to a weak health care system and low economic conditions, Pakistan’s population, in general, already suffers from many comorbidities, which can severely affect the outcome of patients infected with COVID-19. Objective COVID-19 infections are coupled with a manifestation of various notable outcomes that can be documented and characterized clinically. The aim of this study was to examine these clinical manifestations, which can serve as indicators for early detection as well as severity prognosis for COVID-19 infections, especially in high-risk groups. Methods A retrospective observational study involving abstraction of demographic features, presenting symptoms, and adverse clinical outcomes for 1812 patients with COVID-19 was conducted. Patients were admitted to the four major hospitals in the Rawalpindi-Islamabad region of Pakistan, and the study was conducted from February to August 2020. Multivariate regression analysis was carried out to identify significant indicators of COVID-19 severity, intensive care unit (ICU) admission, ventilator aid, and mortality. The study not only relates COVID-19 infection with comorbidities, but also examines other related factors, such as age and gender. Results This study identified fever (1592/1812, 87.9%), cough (1433/1812, 79.1%), and shortness of breath (998/1812, 55.1%) at the time of hospital admission as the most prevalent symptoms for patients with COVID-19. These symptoms were common but not conclusive of the outcome of infection. Out of 1812 patients, 24.4% (n=443) required ICU admission and 21.5% (n=390) required ventilator aid at some point of disease progression during their stay at the hospital; 25.9% (n=469) of the patients died. Further analysis revealed the relationship of the presented symptoms and comorbidities with the progression of disease severity in these patients. Older adult patients with comorbidities, such as hypertension, diabetes, chronic kidney disease, and asthma, were significantly affected in higher proportions, resulting in requirement of ICU admission and ventilator aid in some cases and, in many cases, even mortality. Conclusions Older adult patients with comorbidities, such as hypertension, diabetes, asthma, chronic obstructive pulmonary disorder, and chronic kidney disease, are at increased risk of developing severe COVID-19 infections, with an increased likelihood of adverse clinical outcomes.

Chronic kidney disease (CKD) is associated with accelerated atherosclerosis progression and high incidence of cardiovascular events, hinting that atherosclerotic plaques in CKD may be vulnerable. However, its cause and mechanism remain obscure. Here, it is shown that apolipoprotein E‐deficient (ApoE−/−) mouse with CKD (CKD/ApoE−/− mouse) is a useful model for investigating the pathogenesis of plaque vulnerability, and premature senescence and phenotypic switching of vascular smooth muscle cells (VSMCs) contributes to CKD‐associated plaque vulnerability. Subsequently, VSMC phenotypes in patients with CKD and CKD/ApoE−/− mice are comprehensively investigated. Using multi‐omics analysis and targeted and VSMC‐specific gene knockout mice, VSMCs are identified as both type‐I‐interferon (IFN‐I)‐responsive and IFN‐I‐productive cells. Mechanistically, mitochondrial damage resulting from CKD‐induced oxidative stress primes the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway to trigger IFN‐I response in VSMCs. Enhanced IFN‐I response then induces VSMC premature senescence and phenotypic switching in an autocrine/paracrine manner, resulting in the loss of fibrous cap VSMCs and fibrous cap thinning. Conversely, blocking IFN‐I response remarkably attenuates CKD‐associated plaque vulnerability. These findings reveal that IFN‐I response in VSMCs through immune sensing of mitochondrial damage is essential for the pathogenesis of CKD‐associated plaque vulnerability. Mitigating IFN‐I response may hold promise for the treatment of CKD‐associated cardiovascular diseases., Oxidative stress‐induced mitochondrial damage under chronic kidney disease (CKD) milieu primes the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway in vascular smooth muscle cells (VSMCs) to trigger type‐I‐interferon response, which induces VSMC premature senescence and phenotypic switching in an autocrine/paracrine manner and finally results in plaque vulnerability.

ObjectivesTo highlight common precipitants and co-morbidities of gout in Nigerians; determine the frequency of chronic kidney disease (CKD) in Nigerian gout patients, as well as identify significant associations of CKD in gout patients.Material and methodsRetrospective cross-sectional study of gout cases seen at the Rheumatology Clinic of the Lagos State University Teaching Hospital over five years from January 2011 to December 2015. Gout was diagnosed using the 1977 American Rheumatism Association (ARA) criteria. Clinical and laboratory data were extracted and examined for the presence of CKD defined using Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines as estimated glomerular filtration rate (eGFR, CKD-EPI) < 60 mls/min/1.73 m2 body surface area for > 3 months.ResultsOne hundred and six gout patients were identified representing 4.5% out of a total of 2330 cases seen during the study period. There were 94 males and 12 females. Oligoarthritis was most frequent (41.5%) with the knee mostly affected (20.1%). Diuretic use was the most frequent precipitant (37.9%) with hypertension the commonest co-morbidity (62.9%). Of 70 patients with complete results, 29 had eGFR (CKD-EPI) < 60 mls/min (41.4%). Age, proteinuria, body mass index (BMI) and packed cell volume (PCV) were significant associations of CKD. Gout patients with CKD were significantly older (61.79 vs. 54.41 years, p = 0.003) with a significantly higher proportion developing proteinuria (15 vs. 4 patients, p  0.0001) compared to those without CKD. In contrast, those with CKD had a significantly lower BMI (27.31 vs. 29.65 kg/m2, p = 0.026) and PCV (31.97 vs. 37.95%, p = 0.005).ConclusionsThiazide diuretic use is the most common precipitant while hypertension is the commonest comorbidity in Nigerian gout patients. About two in five Nigerian gout patients had chronic kidney disease at presentation with age, proteinuria, BMI and PCV as significant associations. It is thus imperative to screen for chronic kidney disease when managing gout patients.

Type 2 Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) worldwide, and is associated with an increased risk of left ventricular (LV) hypertrophy, LV systolic and diastolic dysfunctions. The aim of this study was to investigate abnormal echocardiographic findings in patients with CKD with and without DM, and identify the factors associated with these abnormalities. We enrolled 356 pre-dialysis patients with CKD (stages 3–5), including 208 with DM and 148 without DM. The structure and systolic and diastolic functions of the left ventricle were assessed using echocardiography, and the clinical and echocardiographic parameters were analyzed. The patients with DM had higher rates of observed/predicted left ventricular mass > 128% (69.5% vs. 56.7%, p = 0.015), midwall fractional shortening < 14% (22.6% vs. 8.8%, p = 0.001), and ratio of peak early transmitral filling wave velocity to early diastolic velocity of lateral mitral annulus > 12 (32.7% vs. 16.2%, p < 0.001) than those without DM. Multivariate analysis showed that male sex, a history of smoking, high systolic blood pressure, high body mass index, high levels of fasting glucose and total cholesterol, low levels of albumin and hemoglobin, and a low estimated glomerular filtration rate were associated with abnormal echocardiographic findings. The rates of inappropriate left ventricular mass, systolic and diastolic dysfunction were higher in our patients with CKD and DM than in those without DM.

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome in humans, that is an endemic disease in Finland. We estimated the seroprevalence of PUUV in Finland and explored risk factors and disease associations by using unique survey data with health register linkage. A total of 2000 sera from a nationwide health survey from 2011, representative of the adult population, were screened for PUUV IgG by immunofluorescence assay. We performed statistical analysis adjusting for stratified cluster design and taking into account sampling weights. In total, 254 sera among 2000 tested were PUUV-IgG-positive resulting in a weighted seroprevalence of 12.5%, (95% CI 10.9–14.4), mirroring known age and regional variation in reported incidence. No associations between PUUV-seropositivity and chronic diseases including cardiovascular (including hypertension), pulmonary, kidney disease and cancer were observed. Smoking was significantly associated with seropositivity (adjusted OR 1.54; 95% CI 1.16–2.04). In addition, significant dose-response relations were found for the number of cigarettes smoked daily (OR 1.14; 95% CI 1.12–1.28). The results are important for disease burden assessment and guide intervention strategies, highlighting also the role of smoking prevention.

Background: Chronic kidney disease (CKD) and inflammation play critical roles in atherosclerosis. There is limited evidence regarding the relationship between CKD and patients receiving second-generation drug-eluting stents for coronary artery disease. Objective: This study aimed to investigate the effect of CKD on cardiovascular and renal events in patients undergoing percutaneous coronary intervention (PCI) with everolimus-eluting stents (EES). Methods: We analyzed 504 consecutive patients with stable angina pectoris and significant coronary artery stenosis treated with EES. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 before coronary angiography. The primary outcome was the occurrence of major adverse renal and cardiovascular events (MARCE) including cardiac death, revascularization, heart failure, cerebral infarction, worsening renal function > 25% from baseline, and renal replacement therapy at 1 year. Results: Patients were divided into the a MARCE (n = 126) and a non-MARCE (n = 378) group. The incidence of CKD was 51% in all subjects (including those on hemodialysis) and was significantly higher in the MARCE group than in the non-MARCE group (p = 0.00001). Multivariate logistic regression analysis identified that CKD was independently associated with MARCE (adjusted odds ratio 2.03, 95% confidence interval 1.21–3.39, p = 0.007). Patients were divided into four groups based on CKD and C-reactive protein (CRP) level prior to initial coronary angiography. Cox proportional hazards analysis revealed that patients with CKD and high CRP (≥0.3 mg/dL) had the worst prognosis (hazard ratio 4.371, 95% confidence interval 2.634–7.252, p = 0.00001) compared to patients without CKD and with low CRP. Conclusion: CKD combined with CRP predicted more clinical events in patients undergoing PCI with EES.

Energy restriction (ER) has been widely studied as a novel intervention, and its ability to prolong life has been fully demonstrated. For example, ER can significantly extend the lifespans of model flies, worms, rodents and other mammals. The role of ER in renal protection has also been elucidated. In preclinical studies, adjusting total energy intake or consumption of specific nutrients has prophylactic or therapeutic effects on ageing-related kidney disease and acute and chronic kidney injury. Amino acid restriction has gradually attracted attention. ER mimetics have also been studied in depth. The protective mechanisms of ER and ER mimetics for renal injury include increasing AMP-activated protein kinase and sirtuin type 1 (Sirt1) levels and autophagy and reducing mammalian target of rapamycin, inflammation and oxidative stress. However, the renal protective effect of ER has mostly been investigated in rodent models, and the role of ER in patients cannot be determined due to the lack of large randomised controlled trials. To protect the kidney, the mechanism of ER must be thoroughly researched, and more accurate diet or drug interventions need to be identified.

Purpose Renal cortical perfusion measured in noninvasive, dynamic ultrasonic method is connected with the hemodynamic cardiac properties and renal function. Antihypertensive drugs affect the functioning of the heart and kidneys. The aim of the study was to evaluate the effect of a chronic use of antihypertensive drugs on ultrasound parameters of renal cortical perfusion. Methods The study included 56 consecutive patients (49 M + 7 F, age 54.0 ± 13.3) with stable chronic kidney disease and hypertension. Color Doppler dynamic tissue perfusion measurement was used to assess renal cortical perfusion. Results Patients were treated with a mean of 2.7 ± 1.4 antihypertensive drugs, of which diuretics accounted for 25%, angiotensin-converting enzyme inhibitors (ACE-I) together with angiotensin receptor blockers (ARB) 24%, beta-blockers (BB) 23%, calcium channel blockers 16%, alpha-1 blockers (α1B) 9% and centrally acting drugs 3%. All investigated groups of drugs correlated significantly with parameters of renal perfusion. In multivariable regression analyses adjusted to age, diuretics were connected with the decrease (r = − 0.473) and ACE-I + ARB (r = 0.390) with the improvement of proximal and whole renal cortex perfusion (R2 = 0.28; p

Significant impairment of left ventricular function causes low cardiac output syndrome in the immediate postoperative period in 3-14% of patients undergoing surgery, increasing the mortality 15-fold.To assess the use of levosimendan in patients undergoing cardiac surgery in 2016.The analysis included 14 patients: 3 (21.4%) women and 11 (78.6%) men aged 65.4 ±11.8 years. The mean value of left ventricular ejection fraction amounted to 20 ±6.25%. In 11 patients, levosimendan infusion was started immediately after the induction of anesthesia. Three patients received the agent during the early postoperative period due to low cardiac output syndrome refractory to conventional therapy. The dosage was modified within the range of 0.05-0.2 μg/kg/min. On the day of the surgery, all patients received continuous infusion of adrenaline and levonor.The cardiac index amounted to 2.8 ±0.71 l/mLevosimendan therapy proved safe in the study group. The nature of the study and the small sample size preclude the formulation of detailed conclusions.Istotne upośledzenie funkcji lewej komory serca jest przyczyną zespołu małego rzutu w bezpośrednim okresie pooperacyjnym. Dotyczy 3–14% operowanych chorych, śmiertelność w takich przypadkach wzrasta 15-krotnie.Oceniono zastosowanie lewosimendanu u chorych poddawanych zabiegom kardiochirurgicznym w 2016 roku.Analizą objęto 14 pacjentów, w tym 3 (21,4%) kobiety i 11 (78,6%) mężczyzn w wieku 65,4 ±11,8 roku. Średnia wartość frakcji wyrzutowej lewej komory serca wynosiła 20 ±6,25%. U 11 pacjentów infuzję lewosimendanu rozpoczęto bezpośrednio po indukcji znieczulenia. Trzech chorych otrzymało lek we wczesnym okresie pooperacyjnym z powodu zespołu małego rzutu, niepoddającego się konwencjonalnej terapii. Dawkę lewosimendanu modyfikowano w zakresie wartości 0,05–0,2 μg/kg/min. W pierwszej dobie operacji wszyscy chorzy otrzymywali wlew ciągły adrenaliny i lewonoru.Indeks sercowy w kilka godzin po rozpoczęciu infuzji wynosił 2,8 ±0,71 l/mW badanej grupie terapia lewosimendanem okazała się bezpieczna. Charakter badania i mała liczba pacjentów nie pozwala na formułowanie szczegółowych wniosków.

Objective: The aim of this study was to examine the effect of volume status on the progressions of renal disease in normovolemic and hypervolemic patients with advanced non-dialysis-dependent chronic kidney disease (CKD) who were apparently normovolemic in conventional physical exam­ination. Materials and Methods: This was a prospective interventional study performed in a group of stage 3–5 CKD patients followed up for 1 year. Three measurements were made for volume and renal status for every patient. The fluid status was assessed by a bioimpedance spectroscopy method. A blood pressure (BP) value > 130/80 mm Hg prompted the initiation or dose increment of diuretic treatment in normovolemic patients. Result: Forty-eight patients (48%) were hypervolemic. At the end of the 1-year follow-up, hypervolemic patients were found to have a significantly lower estimated glomerular filtration rate and higher systolic BP compared to baseline. Hypervolemia was associated with an increased incidence of death. Conclusion: We have shown that maintenance of normovolemia with diuretic therapy in normovolemic patients was able to slow down and even improve the progression of renal disease. Volume overload leads to an increased risk for dialysis initiation and a decrease in renal function in advanced CKD. Volume overload exhibits a stronger association with mortality in CKD patients.

Purpose To describe the patient characteristics, treatments, disease monitoring, and kidney function of patients with sporadic angiomyolipoma (sAML), stratified by the number and size of renal angiomyolipomas (AMLs). Methods Single-center retrospective analysis of patients with sAML treated from 1990 to 2015 in a dedicated clinic for inheritable tumor syndromes in a tertiary referral center from the Netherlands. Patients’ first AML assessment at the clinic was defined as the index date. Patient characteristics were measured at the index date. Treatments, disease monitoring, and kidney function were measured post-index date. Results The study sample included 53 patients followed for a total of 184.6 patient-years. At the index date, the largest AML was ≥ 3.5 cm for 26 patients and

Cabozantinib and lenvatinib have been approved for the treatment of progressive medullary thyroid cancer and radioiodine-resistant thyroid cancer, respectively. Both phase III trials of cabozantinib and lenvatinib reported that renal adverse events (AEs) rarely occurred. The cabozantinib phase III study reported no AEs related to renal toxicity. In the lenvatinib phase III trial grade 3 (CTCAE), proteinuria (urinary protein ≥3.5 g/24 h) was found in 10.0% of the lenvatinib and 0.0% of the placebo patients. We report a 23-year-old patient with metastatic medullary thyroid cancer who was enrolled in the phase III trial, comparing cabozantinib to placebo and a 67-year-old patient with metastatic, papillary thyroid carcinoma who was undergoing treatment with lenvatinib during his enrollment in the phase III trial. The first patient had a normal kidney function initially, but developed end-stage chronic kidney disease unexpectedly on cabozantinib and additional zoledronate infusion. Whereas the second patient suffered from a dramatic aggravation of his known mild chronic renal insufficiency (KDOQI stage 2) due to long standing hypertension and atherosclerosis during the treatment with lenvatinib. These severe AEs due to anti-VEGF tyrosine kinase inhibitor treatment were unknown so far. In conclusion, these 2 cases argue for increased awareness for the possibility of renal failure as a consequence of anti-VEFG treatment. Predisposing conditions like known mild chronic renal insufficiency with only mild proteinuria and with atherosclerosis or precipitating co-medications like zoledronate infusion need to be accounted for to prevent these severe AEs.

Background Patients and stakeholders are increasingly engaging in health research to help address evidence-practice gaps and improve health-care delivery. We previously engaged patients, caregivers, health-care providers (HCPs) and policymakers in identifying priorities for chronic kidney disease (CKD) research. Objective We aimed to explore participants' views on the research priorities and prioritization process 2 years after the exercise took place. Design In this qualitative descriptive study, individual interviews were conducted and analysed using an inductive, thematic analysis approach. Setting/participants Participants resided across Canada. We purposively sampled across stakeholder groups (CKD patients, caregivers, HCPs and policymakers) and types of engagement (wiki, workshop and/or steering committee) from the previous CKD priority-setting project. Results Across 23 interviews, participants discussed their research priorities over time, views on the prioritization process and perceived applicability of the priorities. Even though their individual priorities may have changed, participants remained in agreement overall with the previously identified priorities, and some perceived a distinction between patient and HCP priorities. They tended to balance individual priorities with their broader potential impact and viewed the prioritization process as systematic, collaborative and legitimate. However, participants acknowledged challenges to applying the priorities and emphasized the importance of communicating the project's outcomes upon its completion. Conclusion Two years after engaging in CKD research prioritization, stakeholder participants remained in agreement with the previously identified priorities, which they felt reflected group deliberation and consensus. Rapport and communication were highlighted as key elements supporting effective engagement in research prioritization.

Background For several major chronic diseases including asthma, chronic obstructive pulmonary disease, chronic kidney disease, and diabetes, a state-of-the-art method to avert poor outcomes is to use predictive models to identify future high-cost patients for preemptive care management interventions. Frequently, an American patient obtains care from multiple health care systems, each managed by a distinct institution. As the patient’s medical data are spread across these health care systems, none has complete medical data for the patient. The task of building models to predict an individual patient’s cost is currently thought to be impractical with incomplete data, which limits the use of care management to improve outcomes. Recently, we developed a constraint-based method to identify patients who are apt to obtain care mostly within a given health care system. Our method was shown to work well for the cohort of all adult patients at the University of Washington Medicine for a 6-month follow-up period. It is unknown how well our method works for patients with various chronic diseases and over follow-up periods of different lengths, and subsequently, whether it is reasonable to perform this predictive modeling task on the subset of patients pinpointed by our method. Objective To understand our method’s potential to enable this predictive modeling task on incomplete medical data, this study assesses our method’s performance at the University of Washington Medicine on 5 subgroups of adult patients with major chronic diseases and over follow-up periods of 2 different lengths. Methods We used University of Washington Medicine data for all adult patients who obtained care at the University of Washington Medicine in 2018 and PreManage data containing usage information from all hospitals in Washington state in 2019. We evaluated our method’s performance over the follow-up periods of 6 months and 12 months on 5 patient subgroups separately—asthma, chronic kidney disease, type 1 diabetes, type 2 diabetes, and chronic obstructive pulmonary disease. Results Our method identified 21.81% (3194/14,644) of University of Washington Medicine adult patients with asthma. Around 66.75% (797/1194) and 67.13% (1997/2975) of their emergency department visits and inpatient stays took place within the University of Washington Medicine system in the subsequent 6 months and in the subsequent 12 months, respectively, approximately double the corresponding percentage for all University of Washington Medicine adult patients with asthma. The performance for adult patients with chronic kidney disease, adult patients with chronic obstructive pulmonary disease, adult patients with type 1 diabetes, and adult patients with type 2 diabetes was reasonably similar to that for adult patients with asthma. Conclusions For each of the 5 chronic diseases most relevant to care management, our method can pinpoint a reasonably large subset of patients who are apt to obtain care mostly within the University of Washington Medicine system. This opens the door to building models to predict an individual patient’s cost on incomplete data, which was formerly deemed impractical. International Registered Report Identifier (IRRID) RR2-10.2196/13783

Background It is well established that single pill combination (SPC) therapies have the potential to improve patient adherence versus multi-pill regimens, thereby improving blood pressure control and clinical outcomes in populations with hypertension. Purpose To develop a microsimulation model, capturing different treatment pathways, to project the impact on clinical outcomes of using single pill combination therapies for the management of hypertension in five countries (Italy, Russia, China, South Korea and Mexico). Methods The model was designed to project health outcomes between 2020 and 2030 for populations with hypertension managed according to four different treatment pathways: current treatment practices [CTP], single drug with dosage titration first then sequential addition of other agents [start low and go slow, SLGS], free choice combination with multiple pills [FCC] and combination therapy in the form of a single pill [SPC]. Model inputs were derived from Global Burden of Disease 2017 dataset, including demographics, health status/risk factors, transition probabilities and treatment attributes/healthcare utilization, and the model incorporated real-world challenges to healthcare delivery such as access to care, SBP measurement error, adherence and therapeutic inertia. Simulated outcomes of mortality, incidence of chronic kidney disease (CKD), stroke and ischemic heart disease (IHD), and disability-adjusted life years (DALYs) due to these conditions were estimated for population of 1,000,000 simulated patients for each treatment pathway and country. Results SPC therapy was projected to improve health outcomes over SLGS, FCC and CTP over 10 years in all five countries. SPC was forecast to reduce mortality by 5.4% (Italy), 4.9% (Russia), 4.5% (China), 2.3% (South Korea) and 3.6% (Mexico) versus CTP and showed greater projected reductions in mortality than SLGS and FCC. DALYs were projected to be reduced with SPC therapy by between 5.7% (Italy) and 2.2% (South Korea) compared with CTP and reductions in the incidence of clinical events were also projected with SPC therapy, with decreases in the range of 11.5% (Italy) to 4.9% (South Korea) versus CTP. Conclusions Ten-year projections of clinical outcomes associated with different anti-hypertensive treatment pathways in five countries indicated that both combination therapies (FCC and SPC) are likely to reduce the disease burden of hypertension compared with conventional management approaches, with SPC showing the greatest overall benefits due to improved adherence. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi, Gentilly, France

// Cheng-Yi Chen 1, 2, 3 , Cheng-Jui Lin 2, 4, 5 , Chih-Sheng Lin 3 , Fang-Ju Sun 2, 6 , Chi-Feng Pan 2, 4 , Han-Hsiang Chen 2, 4 and Chih-Jen Wu 4, 5, 7, 8 1 Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Hsinchu, Taiwan 2 MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan 3 Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan 4 Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan 5 Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 6 Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan 7 Graduate Institute of Medical Sciences and Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 8 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan Correspondence to: Chih-Jen Wu, email: wcjyali@yahoo.com.tw Keywords: liver cirrhosis; chronic kidney disease; diabetes mellitus; estimated glomerular filtration rate; MELD score Received: June 02, 2017 Accepted: August 29, 2017 Published: December 18, 2017 ABSTRACT Background: Chronic kidney disease (CKD) in cirrhosis is one of the dreaded complications associated with a steep rise in mortality and morbidity, including diabetes. There are limited data on the prevalence of CKD and the association with diabetes in outpatients with cirrhosis. Methodology: This is a cross-sectional study of 7,440 adult liver cirrhosis patients enrolled from August 2001 to April 2010 in a medical center. Case control matching by age and sex with 1,967 pairs, and conditional logistic regression for odds of diabetes was analyzed using adjusted model. Results: CKD was present in 46.0%, 45.7% and 45.6% of the study population using the MDRD-6, CKD-EPI and MDRD-4 estimated glomerular filtration rate (eGFR) equations, respectively. Using a conditional logistic regression model after adjusting for other risk factors, odds for diabetes increased significantly compared with non-CKD in CKD stage 3 to 5 (stage 3~5) based on MDRD-6–adjusted model, ORs were: stage 3~5, 2.34 (95% CI, 1.78-3.01); MDRD-4–adjusted model, ORs were: stage 3~5, 8.51 (95% CI, 5.63-11.4); CKD-EPI–adjusted model, ORs were: stage 3~5, 8.61 (95% CI, 5.13-13.9). Conclusion: In cirrhosis patients, prevalence of diabetes was higher in patients with advanced stage of CKD. For patients with cirrhosis, patients with CKD stages 3~5 defined by MDRD-4, MDRD-6, and CKD-EPI eGFR equations had increased risk for diabetes. More severe cirrhosis, indicated by the Child-Turcott-Pugh classification was also accompanied by an increased risk for diabetes.

// Wei-Hao Hsu 1, 2 , Pi-Jung Hsiao 1, 3 , Pi-Chen Lin 1 , Szu-Chia Chen 2, 3, 4, 5 , Mei-Yueh Lee 1, 2, 3, 4 and Shyi-Jang Shin 1, 3, 6 1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan Correspondence to: Mei-Yueh Lee, email: lovellelee@hotmail.com Keywords: metformin; diabetes mellitus; chronic kidney disease; renal function decline; estimated glomerular filtration rate Received: September 12, 2017 Accepted: December 04, 2017 Published: December 17, 2017 ABSTRACT Background: Impaired renal function can lead to the accumulation of metformin, and elevated concentrations of metformin have been associated with lactic acidosis. The aim of this study was to evaluate the effect of continuous metformin treatment in patients with type 2 diabetes mellitus (DM) and moderate chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 30–0 ml/min/1.73 m 2 ) on renal function. Methods: A total of the 616 patients were enrolled from the research database of Kaohsiung Medical University Hospital from January 1 to 2009 and December 31, 2013. The patients were divided into two groups: those who continued metformin treatment (continuation group; n = 484), and those who discontinued metformin treatment for at least 100 days (interruption group; n = 132). Results: The slope of eGFR in the metformin interruption group was statistically lower than that in the metformin continuation group (0.75 ± 0.76 vs. –1.32 ± 0.24 mL/min/1.73 m 2 /year, p = 0.0007). After adjusting for baseline covariates in the multivariate linear regression analysis, the continuation of metformin (unstandardized coefficient β, –2.072; 95% confidence interval, –3.268– –0.876) was a risk factor for the patients with DM and moderate CKD. Conclusions: Metformin may have an adverse effect on renal function in patients with type 2 DM and moderate CKD.

Objectives: To evaluate the changing spectrum of kidney diseases over time in China using renal biopsy-proven cases. Methods: All patients over the age of 14 years who were diagnosed with a kidney disease by renal biopsy in the Renal Biopsy Registry of the National Clinical Research Center of Kidney Diseases in Jinling Hospital, Nanjing, from 2003 to 2014 were included. Results: In total, 40,759 cases of renal biopsy were analyzed. The mean age of the patients was 36.59 ± 14.12 years. 52.0% of the patients were male. Primary glomerulonephritis (PGN), secondary glomerulonephritis, tubulointerstitial disease, and hereditary renal diseases accounted for 67.1, 26.4, 2.9, and 2.5%, respectively. IgA nephropathy (IgAN), membranous nephropathy (MN), minimal change disease, and focal segmental glomerulosclerosis were the leading PGN diagnoses. The frequency of MN increased significantly (p < 0.001) by doubling from 2003 to 2014. An analysis by age category indicated that the frequency of MN increased significantly over time (p < 0.001) in all age categories and increased by more than 2 times in the 14-24 age category. Lupus nephritis (LN) and Henoch-Schönlein purpura nephritis (HSPN) decreased significantly (p < 0.001), diabetic nephropathy (DN) increased nearly twice (p < 0.001), monoclonal immunoglobulin deposition disease (MIDD) tripled (p < 0.001), and hypertensive nephropathy (HT) (p < 0.001) and renal amyloidosis (AMY) (p < 0.05) showed an upward trend. An analysis by age category showed that hepatitis B-related nephritis has significantly decreased in the 14-24 age category (p < 0.001). Conclusion: PGN continued to be the predominant kidney disease in China with IgAN being the most common PGN. The frequency of MN increased significantly, with a maximum increase in young adults. LN and HSPN decreased significantly, DN and MIDD increased significantly, and HT and AMY also showed an increasing trend. The kidney disease trends presented in this study serve as a reference point for patient care, disease prevention, and public health interventions.

Increasing evidence suggests that lipid variability may be a predictor of cardiovascular events. However, few studies have evaluated the association between lipid variability and renal outcomes in patients with moderate-to-advanced chronic kidney disease (CKD). Therefore, the aims of this study were to assess whether lipid variability is associated with progression to dialysis in patients with CKD stage 3-5, and to evaluate the risk factors of lipid variability. This longitudinal study enrolled 725 patients with CKD stage 3-5. Intra-individual lipid variability was defined as the standard deviations (SDs) of lipid levels. The renal end-point was defined as commencing dialysis. During a mean follow-up period of 3.2 years, 208 patients (28.7%) started dialysis. The patients with CKD stage 3 with high low-density lipoprotein (LDL) cholesterol SD (per 1 mg/dL; hazard ratio, 1.035; 95% confidence interval, 1.003 to 1.067; p = 0.003) were associated with an increased risk of progression to dialysis, however this association was not seen in the patients with CKD stage 4 or 5. Furthermore, in the patients with CKD stage 3, a high urine protein-to-creatinine ratio (p < 0.001) and the use of statins (p < 0.001) were significantly associated with an increased LDL-cholesterol SD. Greater LDL-cholesterol variability was associated with an increased risk of progression to dialysis in patients with CKD stage 3, but not in those with CKD stage 4 or 5. These findings support the potential role of aggressive lipid control on clinical outcomes and highlight its importance in patients with CKD stage 3.

Many stressors that are encountered upon kidney injury are likely to trigger endoplasmic reticulum (ER) stress, subsequently activating transcriptional, translational and metabolic reprogramming. Monitoring early cellular adaptive responses engaged after hemodynamic impairment yields may represent a clinically relevant approach. However, a non-invasive method for detecting the ER stress response has not been developed. We combined a metabolomic approach with genetic marker analyses using urine from individuals undergoing scheduled cardiac surgery under cardiopulmonary bypass to investigate the feasibility and significance of monitoring the ER stress response in the kidney. We developed an original method based on fragment analysis that measures urinary levels of the spliced X-box binding protein 1 (sXBP1) mRNA as a proxy of inositol-requiring enzyme 1α (IRE1α) activity because sXBP1 is absolutely sensitive and specific for ER stress. The early engagement of the ER stress response after ischemic stress is critical for protecting against tissue damage, and individuals who mount a robust adaptive response are protected against AKI. The clinical consequences of our findings are of considerable importance because ER stress is involved in numerous conditions that lead to AKI and chronic kidney disease; in addition, the detection of ER stress is straightforward and immediately available in routine practice., Highlights • Endoplasmic Reticulum (ER) stress is involved in the pathophysiology of numerous kidney diseases. • We developed a method based on fragment analysis that measures urinary levels of XBP1 mRNA to detect renal ER stress. • ER stress occurs early after cardiopulmonary bypass, a procedure leading to acute kidney injury. • The detection of renal ER stress in this context can predict the occurrence of acute kidney injury. The better care of patients with kidney disease requires the identification of biomarkers of ongoing tissue injury to provide therapies to slow disease progression. In this study, we have developed for the first time a non-invasive (urinary) biomarker of a protective cellular process called Endoplasmic Reticulum stress that occurs early in the kidney after ischemic injury. Renal ischemic injury follows cardiac surgery and could lead to acute kidney injury. Our results indicate that the early detection of individuals who do not activate Endoplasmic Reticulum stress could help to identify individuals who will develop acute kidney injury.

// Jun-Jun Zhang 1, 2, * , Liu Yang 1, 2, * , Jun-Wen Huang 1, 2 , Yu-Jie Liu 3 , Jin-Wei Wang 4 , Lu-Xia Zhang 4 , Ming-Hui Zhao 4 and Zhang-Suo Liu 1, 2 1 Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 2 Research Institute of Nephropathy, Zhengzhou University, Zhengzhou, Henan, China 3 Department of Nephrology and Rheumatology, Children’s Hospital of Zhengzhou City, Zhengzhou, Henan, China 4 Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China * These authors contributed equally to this work Correspondence to: Zhang-Suo Liu, email: zhangsuoliu@sina.com Keywords: chronic kidney disease; diabetes mellitus; clinical traits; medication; diabetic nephropathy Received: March 02, 2017 Accepted: October 13, 2017 Published: November 10, 2017 ABSTRACT Although the prevalence of chronic kidney disease (CKD) and diabetes mellitus (DM) is increasing globally, information on Chinese CKD patients with DM is lacking. A total of 3499 pre-dialysis CKD patients from across China were enrolled in the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) between November 2011 and April 2016. We divided the C-STRIDE patients into CKD with DM and CKD without DM groups and compared their clinical, demographic, and laboratory data in this cross-sectional study. CKD patients with DM were older, had a higher male-to-female ratio, and had more complications than CKD patients without DM. Age, smoking, and 24-h urinary protein levels were associated with co-occurrence of CKD and DM. Less than 50% of patients in either group took antilipemic, cardiovascular, cerebrovascular, or anti-anemic drugs. In addition, only 18.38% of CKD patients with DM had undergone a renal biopsy, and diabetic nephropathy was confirmed in 35.4% of them. Our findings suggest that several types of medication and renal biopsies should be used more frequently in the treatment of Chinese CKD patients with DM.

Background/aims Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters. Methods Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonulin, hepcidin-25, soluble transferrin receptor, interleukin-6 and high-sensitivity C-reactive protein were measured using commercially available assays. Results Zonulin was significantly lower among patients with CKD in comparison with healthy volunteers. There were no statistically significant differences in zonulin concentration between patients with and without inflammation. Zonulin was significantly correlated with hepcidin only in patients with inflammation. Zonulin was neither related to iron nor related to ferritin. Conclusions Zonulin cannot be considered as an inflammatory marker in CKD. It does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated.

Combined therapy with exendin-4 (Ex4) and allogenic adipose-derived mesenchymal stem cells (ADMSC) was tested against either therapy alone for protecting kidney function against chronic kidney disease (CKD) complicated by sepsis syndrome (SS) [i.e., by intraperitoneal injection of cecal-derived bacteria (1.0 × 104) cells/milliliter/total 5.0 cc].Adult-male-Sprague Dawley rats (n=36) were equally divided into group 1 (sham-control), group 2 (CKD), group 3 (CKD-SS), group 4 (CKD-SS-Ex4), group 5 (CKD-SS-ADMSC) and group 6 (CKD-SS-Ex4-ADMSC). At day 42 after CKD induction SS was induced. Thirty-minutes after SS induction, ADMSCs (2.0 ×106 cells) were intravenously administered to groups 5 and 6. Ex4 (10 μg/kg) was intraperitoneally administered groups 4 and 6 at 30 min and days 1 to 5 after SS induction. Animals were euthanized at day 47 after CKD induction. Kidney-injury score, collagen-deposition area, and creatinine/BUN levels were lowest in group 1, highest in group 3 and significantly higher in group 2 than in groups 4 to 6 in a progressively increasing manner (all P0.0001). Cellular expressions of inflammatory (CD14/CD68) and glomerulus/tubular-injury (WT-1/KIM-1) biomarkers displayed an identical pattern, whereas glomerulus/podocyte-component (dystroglycan/nephrin/ZO-1/fibronectin/p-cadherin) biomarkers showed an opposite kidney-injury score among the six groups (all P

// Hirotake Kodama 1 , Shingo Hatakeyama 1 , Naoki Fujita 1 , Hiromichi Iwamura 1, 2 , Go Anan 1, 2 , Ken Fukushi 1 , Takuma Narita 1 , Toshikazu Tanaka 1 , Yuka Kubota 1 , Hirotaka Horiguchi 1 , Masaki Momota 1 , Koichi Kido 1 , Teppei Matsumoto 1 , Osamu Soma 1 , Itsuto Hamano 1 , Hayato Yamamoto 1 , Yuki Tobisawa 1 , Tohru Yoneyama 3 , Takahiro Yoneyama 1 , Yasuhiro Hashimoto 3 , Takuya Koie 1 , Hiroyuki Ito 4 , Kazuaki Yoshikawa 5 , Atsushi Sasaki 6 , Toshiaki Kawaguchi 7 , Makoto Sato 2 and Chikara Ohyama 1, 3 1 Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan 2 Department of Urology, Tohoku Medical and Pharmaceutical University, Sendai, Japan 3 Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan 4 Department of Urology, Aomori Rosai Hospital, Hachinohe, Japan 5 Department of Urology, Mutsu General Hospital, Mutsu, Japan 6 Department of Urology, Tsugaru General Hospital, Goshogawara, Japan 7 Department of Urology, Aomori Prefectural Central Hospital, Aomori, Japan Correspondence to: Shingo Hatakeyama, email: shingoh@hirosaki-u.ac.jp Keywords: upper urinary tract urothelial carcinoma, radical nephroureterectomy, chronic kidney disease, renal function, oncological outcome Received: July 19, 2017 Accepted: July 28, 2017 Published: August 24, 2017 ABSTRACT Objective: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes in patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy. Methods: A total of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017 were retrospectively examined. Oncological outcomes, including intravesical recurrence-free, visceral recurrence-free, cancer-specific, and overall survival rates (intravesical RFS, visceral RFS, CSS, and OS, respectively) stratified by preoperative CKD status (CKD vs. non-CKD) were investigated. Cox proportional hazards regression analysis was performed using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and a prognostic factor-based risk stratification nomogram was developed. Results: Of the 426 patients, 250 (59%) were diagnosed with CKD before radical nephroureterectomy. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS after radical nephroureterectomy were significantly shorter in the CKD group than in the non-CKD group. Background-adjusted IPTW analysis demonstrated that preoperative CKD was significantly associated with poor visceral RFS, CSS, and OS after radical nephroureterectomy. Intravesical RFS was not significantly associated with preoperative CKD. The nomogram for predicting 5-year visceral RFS and CSS probability demonstrated a significant correlation with actual visceral RFS and CSS ( c -index = 0.85 and 0.83, respectively). Conclusions: Upper tract urothelial carcinoma patients with preoperative CKD had a significantly lower survival probability than those without CKD.

// Ji Zhang 2 , Chaosheng Chen 2 , Qiongxiu Zhou 2 , Shubei Zheng 1 , Yinqiu Lv 2 , Jianna Zhang 2 , Xiaohan You 2 , Zhanyuan Li 1 , Zhihong Zhou 1 and Min Pan 1 1 Department of Nephrology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China 2 Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China Correspondence to: Min Pan, email: pm_1234@163.com Keywords: IgA nephropathy, fibrinogen, chronic kidney disease, Oxford classification, renal outcome Received: July 29, 2017 Accepted: September 22, 2017 Published: October 09, 2017 ABSTRACT Background: IgA nephropathy is a primary cause of renal failure, and inflammation and renal fibrosis are the main mechanisms leading to kidney damage. The serum fibrinogen level is closely related to inflammatory states, but its relationship to the prognosis of IgA nephropathy (IgAN) is unclear. Materials and Methods: 1053 patients diagnosed with IgAN after renal biopsy were enrolled from two Nephrology Departments. Demographic and clinical data and histopathological features were collected. The patients were divided into four groups (Q1–Q4) according to the serum fibrinogen levels at the time of renal biopsy, and the relationships of serum fibrinogen levels with other risk factors and the prognosis of IgAN were investigated. Results: 672 patients with proven primary IgAN were included in this study, which included a median follow-up of 36 months. Patients with higher serum fibrinogen levels had elevated serum creatinine levels, 24-hour urinary protein, and blood pressure compared with patients with the lowest levels of serum fibrinogen as well as severe renal damage at the time of renal biopsy. Univariate and multivariate Cox regression analyses confirmed that the serum fibrinogen level at the time of renal biopsy was significantly related to the prognosis of patients with IgAN. Conclusions: In patients with IgAN, an elevated serum fibrinogen level at the time of renal biopsy is associated with poor renal outcomes, which suggests the need for more aggressive early interventions. Greater benefits of aggressive treatments were observed in patients with higher serum fibrinogen levels.

// Chao Ren 1, 2 , Ya-Lin Tong 3 , Jun-Cong Li 2 , Ning Dong 2 , Ji-Wei Hao 2 , Qing-Hong Zhang 2 and Yong-Ming Yao 1, 2, 4 1 School of Medicine, Nankai University, Tianjin 300071, People’s Republic of China 2 Trauma Research Center, First Hospital Affiliated to The Chinese PLA General Hospital, Beijing 100048, People’s Republic of China 3 Department of Burns and Plastic Surgery, The 181st Hospital of Chinese PLA, Guilin 541002, People’s Republic of China 4 State Key Laboratory of Kidney Disease, The Chinese PLA General Hospital, Beijing 100853, People’s Republic of China Correspondence to: Yong-Ming Yao, email: c_ff@sina.com Keywords: HMGB1, sepsis, lateral ventricles, antagonists, brain injuries Received: July 29, 2016 Accepted: September 04, 2017 Published: October 05, 2017 ABSTRACT Sepsis induced brain injury acts as an acute complication and accounts for deterioration and high mortality rate of septic condition. HMGB1 is a late inflammatory mediator that plays a critical role in brain dysfunction and diseases. However, the role of HMGB1 in sepsis induced brain dysfunction remains intricate. The current study investigated the effect of HMGB1 on brain injury in septic mice model with intracerebroventricular injection of BoxA (a specific antagonist of HMGB1). The expression of HMGB1, morphological changes of brain tissues, apoptosis of brain cells, and alteration of behavior were determined. The expressions of HMGB1 in cortex, hippocampus, and striatum were significantly enhanced in the sepsis group when compared with the sham group. In septic conditions, brain tissues showed significant abnormalities in tissue structure, and increased apoptosis of brain cells which was caspase-3 dependent. Septic mice showed suppression of locomotor activity and impairment of memory and learning. Neutralizing brain HMGB1 significantly improved brain injury and apoptosis of brain cells, and further ameliorated disturbed locomotor activities and damaged memory and learning. However, no significant improvement of survival rate was seen after inhibiting central HMGB1. These results reveal that HMGB1 is a potential target for ameliorating sepsis induced brain injury with early antagonizing.

Single nucleotide polymorphisms (SNPs) in renin-angiotensin system (RAS) genes are associated with RAS imbalance and chronic kidney disease (CKD). We performed a case-control study and meta-analysis to investigate the association between angiotensinogen (AGT) M235T polymorphism and CKD. A total of 634 patients with end-stage renal disease and 739 healthy controls were studied. We also searched PubMed and the Cochrane Library to identify prospective observational studies published before December 2015. We found that the TT and MT genotypes were associated with a higher risk of CKD than the MM genotype (odds ratio [OR]: 3.56; 95% confidence interval [CI]: 1.14-11.16 and OR: 2.93; 95% CI: 0.91-9.46, respectively). Thirty-eight study populations were included in the meta-analysis. The T allele was associated with a higher risk of CKD than the M allele in all populations (OR: 1.19; 95% CI: 1.08-1.32). The OR was 1.33 in Asians (95% CI: 1.06-1.67) and 1.10 in Caucasians (95% CI: 1.02-1.18). Evaluation of gene-gene and gene-environment interactions using epistasis analysis revealed an interaction between AGT M235T and angiotensin II receptor type 1 A1166C in CKD (OR: 0.767; 95% CI: 0.609-0.965). Genetic testing for CKD in high-risk individuals may be an effective strategy for CKD prevention.

// Liang-Tseng Kuo 1, 2, , Su-Ju Lin 3 , Chi-Lung Chen 1 , Pei-An Yu 1 , Wei-Hsiu Hsu 1, 4, * and Tien-Hsing Chen 5, * 1 Division of Sports Medicine, Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan 2 Chang Gung University of Science and Technology, Chiayi, Taiwan 3 Division of Nephrology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 4 College of Medicine, Chang Gung University, Taoyuan, Taiwan 5 Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan * These authors have contributed equally to this work Correspondence to: Wei-Hsiu Hsu, email: 7572@cgmh.org.tw Tien-Hsing Chen, email: skyheart0826@gmail.com Keywords: total knee arthroplasty; diabetes mellitus; chronic kidney disease; mortality; periprosthetic joint infection Received: August 16, 2017 Accepted: September 24, 2017 Published: October 31, 2017 ABSTRACT Diabetes and chronic kidney disease (CKD) are associated with a higher rate of complications in patients undergoing total knee arthroplasty (TKA). The purpose of this study was to determine the effects of CKD and diabetes in patients after TKA. Diabetic patients who received unilateral primary TKA between January 2008 and December 2011 were enrolled. The follow-up period was more than 6 months. The primary outcome was a TKA-related infection and the secondary outcome was all-cause mortality. The study cohort included 13844 patients who were followed for a mean period of 2 years, of whom 1459 (10.5%) had CKD. The patients with CKD were older than those without CKD (71.6 versus 70.3 years, P

Background: A sex difference in cisplatin-induced nephrotoxicity (CIN) has been reported in human and animal studies. We examined in humans whether it is associated with sex-hormone changes. Methods: In this retrospective nationwide cohort study, we used Taiwan's National Health Insurance Research Database (NHIRD) to identify patients with a history of malignancy and cisplatin treatment. Patients diagnosed with kidney disease before cisplatin treatment and those with sex-organ malignancies were excluded. A diagnosis of kidney disease within 90 days after the first administration of cisplatin was the study outcome. Risk factors were estimated using a Cox regression model. Subgroup analyses were performed based on different women's estrogen levels in phases of childbearing, perimenopause, and postmenopause. Results: A retrospective analysis of the records of 3973 men (mean age: 56.15 ± 12.85 years) and 1154 women (mean age: 56.31 ± 12.40 years) showed that 1468 (36.95%) men and 451 (39.08%) women had a new diagnosis of kidney disease. The risk factors were being > 55 years old, a high comorbidity score, and a history of aminoglycoside treatment. Only postmenopausal women had a significantly higher risk of kidney injury (hazard ratio: 1.28; 95% CI: 1.02-1.61) than did men. Conclusions: Perimenopausal women have a significantly higher risk of CIN than do men, which might be explained by women's higher levels of estrogen. Additional studies on the underlying mechanisms of the sex difference of CIN are needed.

// Po-Chih Chen 1, 2 , Jiun-Chi Huang 3, 4, 5, 6, * , Szu-Chia Chen 3, 4, 5, 6 , Pei-Yu Wu 4, 5 , Jia-Jung Lee 4, 6 , Yi-Wen Chiu 4, 7 , Jer-Ming Chang 4, 6, 8 , Hung-Chun Chen 4, 7 and Yeou-Lih Huang 1, 2, 9, * 1 Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 7 Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 8 Department of Internal Medicine, Kaohsiung Municipal Cijin Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 9 Department of Chemistry, National Sun Yat-sen University, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Jiun-Chi Huang, email: karajan77@gmail.com Yeou-Lih Huang, email: yelihu@kmu.edu.tw Keywords: diabetes mellitus, transmitral E wave velocity, early diastole mitral velocity, chronic kidney disease, cardiovascular event Received: June 16, 2017 Accepted: September 21, 2017 Published: October 10, 2017 ABSTRACT The association between DM and left ventricular diastolic dysfunction, assessed using the ratio of peak early transmitral filling wave velocity (E) to early diastolic velocity of mitral annulus (Ea), with cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) remains uncertain. This study included 356 CKD stage 3–5 patients underwent echocardiography. All patients were classified into four groups based on the presence of DM and E/Ea ≤ or > 9. CV events included CV death, hospitalization for heart failure, unstable angina or nonfatal myocardial infarction, sustained ventricular arrhythmia, transient ischemic attack, and stroke. There were 58 CV events during the mean observation period of 25.0 months. A combination of the presence of DM and E/Ea > 9 (vs . a combination of non-DM and E/Ea ≤ 9) was associated with CV events in unadjusted model (hazard ratio [HR], 6.990; 95% confidence interval [CI], 2.753–17.744; p < 0.001), and in a multivariate adjusted model (HR, 3.037; 95% CI, 2.088–7.177; p = 0.025). In the patients without DM, the E/Ea ratio ( p = 0.033) improved the prediction of CV events, compared to the E/Ea ratio ( p = 0.018), left atrial diameter ( p = 0.016) and left ventricular mass index ( p = 0.001) in the patients with DM. The combination of DM and left ventricular diastolic dysfunction was associated with CV events in patients with CKD stage 3–5. Assessments of DM status and E/Ea ratio may facilitate identifying high-risk patient population of unfavorable CV outcomes.

// Yongqing Shen 2, * , Dan Yu 6, * , Pan Qi 1 , Xuliang Wang 5 , Xiaoqiang Guo 3, 4 and Aili Zhang 1 1 Department of Urology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, Hebei, China 2 Department of Nursing, Hebei University of Chinese Medicine, Shijiazhuang 050020, Hebei, China 3 State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China 4 Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, Guangdong, China 5 Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China 6 Longgang District Central Hospital, Shenzhen 518116, Guangdong, China * These authors have contributed equally to this work Correspondence to: Aili Zhang, email: z13930409899@163.com Xiaoqiang Guo, email: xiaoqiangguo123@163.com Keywords : kidney cancer; calcitriol; cell senescence; JMJD3; p16INK4A Abbreviations : 1,25(OH) 2 VD 3 : 1,25-dihydroxyvitamin D3; JMJD3: Jumonji domain-containing protein 3; VDR: vitamin D receptor Received: July 03, 2017 Accepted: September 29, 2017 Published: October 26, 2017 ABSTRACT Calcitriol, also known as 1,25-dihydroxyvitamin D3 (1,25(OH) 2 VD 3 ), is a biologically active form of vitamin D and has a wide range of anticancer activity against various cancer cell lines. However, the mechanism of calcitriol remains to be further studied. In this study, the biological effect and epigenetic regulation of calcitriol on kidney cancer cells were investigated. Calcitriol can significantly inhibit cell proliferation of kidney cancer cell lines 786-O ( P

// Junnan Wu 1, * , Guangtao Lei 2, * , Xiao Wang 3 , Yuezhong Tang 4 , Huan Cheng 4 , Guihua Jian 1 , Xianfeng Wu 1 and Niansong Wang 1 1 Department of Nephrology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China 2 Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China 3 Department of Endocrinology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China 4 Kangjian Community Health Center, Xuhui District, Shanghai, China * These authors contributed equally to this work Correspondence to: Niansong Wang, email: wangniansong2012@163.com Xianfeng Wu, email: xianfengwu2@163.com Keywords: comorbidities, coronary artery disease, elderly, hyperuricemia, serum uric acid Received: July 03, 2017 Accepted: September 03, 2017 Published: September 19, 2017 ABSTRACT Because many subjects with hyperuricemia have comorbidities, it can be difficult to differentiate the role of hyperuricemia from that of other comorbidities of coronary artery disease (CAD). Subjects aged ≥ 65 years were enrolled in the study and were available at enrollment and at 5-year follow-up. Subjects were excluded if they were overweight or obese, hypertensive, diabetic, hyperlipidemic, had a pre-existing cardiovascular disease, a history of gout or hyperuricemia on medications, or chronic kidney disease as estimated by a glomerular filtration rate (eGFR) 7 mg/dL in men and ≥ 6 mg/dL in women) and normouricemic subjects. A total of 2,142 subjects without comorbidities (mean age of 70.7 ± 5.9 years, 1,194 men) were followed for 57.4 ± 8.9 months. Hyperuricemia was associated with an increased cumulative incidence of incident CAD events (15.0% versus 8.8%, P < 0.001). After adjusting for confounding factors, hyperuricemia independently predicted the risk of incident CAD events (HR=1.71, 95% CI 1.26–2.34). In conclusion, asymptomatic hyperuricemia is a valuable biomarker for predicting the development of incident CAD events.

// Shih-Ting Huang 1, 2 , Ya-Wen Chuang 1 , Tung-Min Yu 1, 3 , Cheng-Li Lin 4, 5 and Long-Bin Jeng 3, 6 1 Division of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan 2 Graduate Institute of Public Health, China Medical University, Taichung, Taiwan 3 Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan 4 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan 5 College of Medicine, China Medical University, Taichung, Taiwan 6 Department of Surgery, Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan Correspondence to: Long-Bin Jeng, email: otc.Jeng@gmail.com Keywords: bleeding, cholangitis, cirrhosis, pancreatitis, polycystic kidney disease Received: May 19, 2017 Accepted: August 07, 2017 Published: September 15, 2017 ABSTRACT Background: The objective of this study was to determine the incidence of major hepatointestinal complications in patients with polycystic kidney disease (PKD). Methods: We analyzed the Taiwan National Health Insurance claims data (2000–2010) of 6031 patients with PKD and 23,976 non-PKD hospitalized controls. The control cohort was propensity score matched with the PKD cohort at a 1:4 ratio. All patients were followed up from the index date to the first inpatient diagnosis of hepatointestinal complications, death, or 31 December, 2011. Cox proportional hazard regression models were used to identify the risk of outcome after adjustment for potential confounders. Results: The incidence rates of acute pancreatitis, cholangitis, peptic ulcer bleeding, and cirrhosis were 5.72, 4.01, 19.9, and 5.46 per 1000 person-years, respectively, in the PKD cohort. Compared with the non-PKD controls, patients with PKD exhibited an increased risk of hospitalization for acute pancreatitis, cholangitis, peptic ulcer bleeding, and cirrhosis (adjusted subhazard ratio [aSHR]: 2.36, 95% confidence interval [95% CI], 1.95–2.84]; 2.36, [95% CI, 1.95–2.84]; 2.41, [95% CI, 1.93–3.01]; 2.41, [95% CI, 2.17–2.67]; and 1.39, [95% CI, 1.16–1.66], respectively; all p < 0.001). PKD, chronic kidney disease, and alcoholism were independent predictors of all these hepatointestinal complications. Kaplan–Meier analysis revealed an increased overall mortality in patients with PKD who developed acute pancreatitis and peptic ulcer bleeding (log-rank p < 0.05). Conclusion: PKD is associated with clinically significant extrarenal complications including acute pancreatitis, cholangitis, peptic ulcer bleeding, and cirrhosis.

// Chiao-Yin Sun 1, 2, 3 , Mei-Ling Cheng 3, 4, 5, 6 , Heng-Chih Pan 1, 2 , Jia-Hung Lee 1, 7 and Chin-Chan Lee 1, 3 1 Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan 2 Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan 3 School of Medicine, Chang Gung University, Taoyuan, Taiwan 4 Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan 5 Clinical Phenome Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan 6 Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 7 Medical Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan Correspondence to: Chiao-Yin Sun, email: fish3970@gmail.com Keywords: uremic toxins, metabolic stress, mitochondrial fusion, mitochondrial mass, mitophagy Received: May 02, 2017 Accepted: July 29, 2017 Published: September 08, 2017 ABSTRACT Protein-bound uremic toxins, indoxyl sulfate and p -cresol sulfate, increase oxidative stress and adversely affect chronic kidney disease progression and cardiovascular complications. In this study, we examined whether mitochondria are the target of indoxyl sulfate and p -cresol sulfate intoxication in vivo and in vitro . The kidneys of 10-week-old male B-6 mice with ½-nephrectomy treated with indoxyl sulfate and p -cresol sulfate were used for the animal study. Cultured human renal tubular cells were used for the in vitro study. Our results indicated that indoxyl sulfate and p -cresol sulfate impaired aerobic and anaerobic metabolism in vivo and in vitro . Indoxyl sulfate and p -cresol sulfate caused mitochondrial fission by modulating the expression of mitochondrial fission–fusion proteins. Mitochondrial dysfunction and impaired biogenesis could be protected by treatment with antioxidants. The in vitro study also demonstrated that indoxyl sulfate and p -cresol sulfate reduced mitochondrial mass by activating autophagic machinery. In summary, our study suggests that mitochondrial injury is one of the major pathological mechanisms for uremic intoxication, which is related to chronic kidney disease and its complications.

// Moshen Mazidi 1,2 , Peyman Rezaie 1,2 , Adriac Covic 3 , Jolanta Malyszko 4 , Jacek Rysz 5 , Andre Pascal Kengne 6 and Maciej Banach 7,8 1 Key State Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China 2 Institute of Genetics and Developmental Biology, International College, University of Chinese Academy of Science, Beijing, China 3 Nephrology Clinic, Parhon University Hospital, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania 4 Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, Bialystok, Poland 5 Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Zeromskiego, Lodz, Poland 6 Non-Communicable Disease Research Unit, South African Medical Research Council and University of Cape Town, Cape Town, South Africa 7 Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland 8 Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland Correspondence to: Mohsen Mazidi, email: // Keywords : telomere length, kidney function, glomerular filtration rate, national health and nutrition examination survey, albumin-creatinine ratio, Gerotarget Received : February 13, 2017 Accepted : May 06, 2017 Published : September 08, 2017 Abstract Background: Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. Objective: We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. Methods: The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. Results: Of the 10568 eligible participants, 48.0% ( n =5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p

Chronic kidney disease (CKD) has diverse phenotypic manifestations including structural (such as fibrosis) and functional (such as glomerular filtration rate and albuminuria) alterations. Gene expression profiling has recently gained popularity as an important new tool for precision medicine approaches. Here we used unbiased and directed approaches to understand how gene expression captures different CKD manifestations in patients with diabetic and hypertensive CKD. Transcriptome data from ninety-five microdissected human kidney samples with a range of demographics, functional and structural changes were used for the primary analysis. Data obtained from 41 samples were available for validation. Using the unbiased Weighted Gene Co-Expression Network Analysis (WGCNA) we identified 16 co-expressed gene modules. We found that modules that strongly correlated with eGFR primarily encoded genes with metabolic functions. Gene groups that mainly encoded T-cell receptor and collagen pathways, showed the strongest correlation with fibrosis level, suggesting that these two phenotypic manifestations might have different underlying mechanisms. Linear regression models were then used to identify genes whose expression showed significant correlation with either structural (fibrosis) or functional (eGFR) manifestation and mostly corroborated the WGCNA findings. We concluded that gene expression is a very sensitive sensor of fibrosis, as the expression of 1654 genes correlated with fibrosis even after adjusting to eGFR and other clinical parameters. The association between GFR and gene expression was mostly mediated by fibrosis. In conclusion, our transcriptome-based CKD trait dissection analysis suggests that the association between gene expression and renal function is mediated by structural changes and that there may be differences in pathways that lead to decline in kidney function and the development of fibrosis, respectively., Graphical Abstract Image 1, Highlights • Gene expression analysis of kidney samples shows the relationship between gene expression and eGFR is mediated by fibrosis • Immune related pathways show the strongest correlation with fibrosis development • Metabolic pathways show a strong correlation with eGFR Chronic kidney disease is characterized by functional changes (glomerular filtration rate, eGFR) and structural changes (mainly renal fibrosis). Gene expression profiles of human kidney samples were analyzed to understand the relationship between these two manifestations. We found that the association between gene expression and eGFR is mediated by fibrosis, suggesting that fibrosis is a crucial determinant of functional kidney decline, and a potential therapeutic target. Gene expression analysis also indicates that fibrosis strongly correlates with immune pathways, and eGFR with metabolic pathways, highlighting potential mechanistic differences between structural and functional manifestations of kidney disease.

Objectives: This pilot study aimed to evaluate the relevance of endocan plasma levels for predicting pulmonary infection after cardiac surgery in patients with chronic kidney disease (CKD). Methods: Serum collected in a previous prospective cohort study (from 166 patients with preoperative CKD who underwent cardiac surgery) was used. Five patients with postoperative pulmonary infection were compared with 15 randomly selected CKD patients with an uneventful outcome. Blood samples were tested at 4 time points (preoperatively and 6, 12, and 24 h after the end of surgery). Endocan, procalcitonin, and C-reactive protein plasma levels were compared between the two groups. Results: At 6 h, the patients with pulmonary infection had significantly higher levels of endocan than the patients without pulmonary infection (24.2 ± 15.6 vs. 6.4 ± 3.2 ng/mL; p = 0.03). A receiver operating characteristic curve analysis showed 80% sensitivity and 100% specificity for endocan to predict pulmonary infection (area under the curve 0.84), with a cutoff value of 15.9 ng/mL. The time saved by assessment of the endocan dosage compared to a clinical diagnosis of pulmonary infection was 47 h. Conclusion: This pilot study showed that a specific study to assess the link between endocan plasma levels and pulmonary infection after cardiac surgery in CKD patients is of potential utility.