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Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Construction land reduction (CLR) is an effective instrument to improve intensive land use, restrict the expansion of construction land, safeguard the requisition-compensation balance of construction land in China, and realize sustainable development. But multiple risks arise from the process of construction land reduction. In that case, identifying and analyzing the key risks of CLR is the prerequisite for formulating practical policy guidelines. This study is conducted to identify the risk factors of CLR and analyze these risks based on expert opinion. Following an in-depth review of the literature, we create a contextual relationship-based model employing an integrated technique of Interpretive Structural Modeling (ISM) and Cross-Impact Matrix Multiplication Applied to Classification (MICMAC) analysis. Based on the ISM and MICMAC analysis, five key risks were identified, and the prevention strategies and policy recommendations for CLR project risks are put forward.

Background: Little is known about the impact of haemodialysis (HD) and peritoneal dialysis (PD) on health-related quality of life (HRQoL). We compared HRQoL between conventional in-centre HD and home-based PD in 1082 newly diagnosed kidney failure patients. Methods: This was an open-label, randomised, non-inferiority trial of adult patients with a diagnosis of end-stage kidney disease (estimated glomerular filtration rate ≤ 15 mL/min/1.73 m2) requiring maintenance dialysis from 36 sites in China randomised 1:1 to receive PD or conventional in-centre HD. The primary outcome was the ‘Burden of Kidney Disease’ assessed using the Kidney Disease Quality of Life-Short Form (KDQoL-SF) survey over 48 weeks and the main secondary outcomes were the remaining scales of KDQoL-SF and all-cause mortality. The effect of PD versus HD on the primary outcome was compared by their geometric mean (GM) ratio, and non-inferiority was defined by the lower bound of a one-sided 95% confidence interval (CI) >0.9. Results: A total of 725 subjects completed the trial per protocol (395 PD and 330 HD, mean age 49.8 (standard deviation (SD) 14.4) years, 41.4% women). For the primary outcome, the mean (SD) change in ‘Burden of Kidney Disease’ over 48 weeks was 2.61 (1.27) in PD group and 2.58 (1.35) in HD group, and the GM ratio (95% CI) was 1.059 (0.908–1.234), exceeding the limit for non-inferiority. For the secondary outcomes, the PD and HD groups were similar in all scales. There were 17 and 31 deaths in PD and HD groups, respectively. Patients receiving PD had more adverse events, adverse event leading to hospitalisation and serious adverse events compared to those allocated to HD, but adverse events leading to death and discontinuation of the trial were not different between PD and HD. Conclusions: In this trial, PD may be non-inferior to HD on the ‘Burden of Kidney Disease’ among Chinese kidney failure patients who are of younger age and have lower comorbidity after 48 weeks’ follow-up.

Background: IgA nephropathy is the most common primary glomerular disease and an important cause of chronic kidney disease. Previous clinical studies have confirmed that Huangkui capsule could reduce urine protein of IgA nephropathy by 100 mg/d losartan potassium. However,the effect of Huangkui capsule on IgA nephropathy is not clear. Methods: Based on two multicenter, large sample phase IV clinical trials (NCT 02231125; NCT 02231138), eligible IgA nephropathy patients were screened and the related data were extracted for secondary analysis. Patients were grouped according to the baseline urinary protein, glomerular filtration rate, or pathologic characteristics using IgA nephropathy Oxford classification and the curative effect was analyzed. Taking the decrease of urine protein ≥30% after Huangkui capsule 6-month treatment as the effective standard, multiple regression analysis was used to analyze the influencing factors of Huangkui capsule in reducing urinary protein in IgA nephropathy patients. Results: 503 patients with IgA nephropathy were enrolled. The efficacy of Huangkui capsule in reducing urinary protein in patients with baseline 24h urinary protein ≥1.0 g/d or glomerular filtration rate ≥60 ml/min reach the effective standard. 24h baseline urinary protein, body mass index, serum albumin, and serum creatinine were the independent influencing factors of Huangkui capsule in reducing urinary protein, but there was no significant correlation with the baseline pathological characteristics. After 6 months of Huangkui capsule treatment, the decrease rate of urine protein increased by 7.9% for every 100mg increase of 24h urinary protein and 6.7% for every 1g/L increase of ALB, while decreased by 1.1% and 7% respectively, for every 1μmmol/L increase of serum creatinine and 1kg/m2 increase of body mass index. Conclusion: The effect of Huangkui capsule is influenced by basic urinary protein, body mass index, serum albumin, and serum creatinine in IgA nephropathy patients. Huangkui capsule can effectively reduce urinary protein in patients with baseline urinary protein ≥1.0 g/d or glomerular filtration rate ≥60 ml/min.

Many enhancers exist as clusters in the genome and control cell identity and disease genes; however, the underlying mechanism remains largely unknown. Here, we introduce an algorithm, eNet, to build enhancer networks by integrating single-cell chromatin accessibility and gene expression profiles. Enhancer network is a gene regulation model we proposed that not only delineates the mapping between enhancers and target genes, but also quantifies the underlying regulatory relationships among enhancers. The complexity of enhancer networks is assessed by two metrics: the number of enhancers and the frequency of predicted enhancer interactions (PEIs) based on chromatin co-accessibility. We apply eNet algorithm to a human blood dataset and find cell identity and disease genes tend to be regulated by complex enhancer networks. The network hub enhancers (enhancers with frequent PEIs) are the most functionally important in enhancer networks. Compared with super-enhancers, enhancer networks show better performance in predicting cell identity and disease genes. The establishment of enhancer networks drives gene expression during lineage commitment. Applying eNet in various datasets in human or mouse tissues across different single-cell platforms, we demonstrate eNet is robust and widely applicable. Thus, we propose a model of enhancer networks containing three modes: Simple, Multiple and Complex, which are distinguished by their complexity in regulating gene expression.Taken together, our work provides an unsupervised approach to simultaneously identify key cell identity and disease genes and explore the underlying regulatory relationships among enhancers in single cells, without requiring the cell type identity in advance.HighlightseNet, a computational method to build enhancer network based on scATAC-seq and scRNA-seq dataCell identity and disease genes tend to be regulated by complex enhancer networks, where network hub enhancers are functionally importantEnhancer network outperforms the existing models in predicting cell identity and disease genes, such as super-enhancer and enhancer clusterWe propose a model of enhancer networks in gene regulation containing three modes: Simple, Multiple and Complex

Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 mThe primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.NCT02063100 on ClinicalTrials.gov.

Background End-stage renal disease patients with maintenance hemodialysis have high-mortality risk. The association of different age of hemodialysis patients with mortality remains uncertain in China. This study aimed to assess the survival outcomes and risk factors affecting mortality between young and elderly patients with maintenance hemodialysis.Methods The multicenter retrospective cohort study enrolled adult patients undergoing maintenance hemodialysis from 24 hemodialysis centers in China between January 1, 2008, and September 30, 2015. The patients were assigned to young and elderly group according to age on the initiation of the hemodialysis. The primary outcome was all-cause mortality of patients. Survival outcomes of patients was performed using a Kaplan-Meier survival analysis. Multivariate cox proportional hazards regression models were implemented to identify risk factors affecting all-cause mortality of patients with maintenance hemodialysis.Results A total of enrolled 1601 patients undergoing maintenance hemodialysis, including 642 young patients and 959 elderly patients. The mean follow-up duration was 48.17 ± 25.59 months, the all-cause mortality was 64 (9.97%) in young group and 255 (26.59%) in elderly group, the hazard ratio [HR] of elderly patients relative to young patients, 1.699 (95% confidence interval [95% CI], 1.482 to 1.949, P＜0.001). The Kaplan-Meier survival curve showed that overall cumulative survival was lower in elderly group than young group (Log Rank tests = 63.31, P＜ 0.001). Multivariate cox regression analysis revealed that the cardiovascular disease (HR, 1.544; 95% CI, 1.103 to 2.161; P = 0.011), cerebrovascular disease (HR, 2.158; 95% CI, 1.309 to 3.557; P = 0.003), lower serum albumin (HR, 1.404; 95% CI, 1.001 to 1.968; P = 0.049), Charlson comorbidity index (CCI) scores with 4-5 (HR, 4.910; 95% CI, 2.327 to 10.357; P＜ 0.001), CCI scores with ≥6 (HR, 9.596; 95% CI, 4.807 to 19.158; P＜ 0.001) were the risk factors associated all-cause mortality of patients.Conclusions The elderly patients undergoing maintenance hemodialysis showed lower survival and higher mortality than young patients in China. Cardiovascular disease, cerebrovascular disease, serum albumin, CCI scores were the risk factors for all-cause mortality of young and elderly patients with maintenance hemodialysis.

IntroductionHyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes. The efficacy and negative effects of currently existing treatment options have made HK management questionable. Sodium zirconium cyclosilicate (SZC), a novel highly selective potassium binder, is approved for the treatment of HK. The present study will be aimed to assess the safety, effectiveness and treatment patterns of SZC in Chinese patients with HK in a real-world clinical setting as it is required by China’s drug review and approval process.Methods and analysisThis is a multicentre, prospective cohort study which plans to enrol 1000 patients taking SZC or willing to take SZC from approximately 40 sites in China. Patients ≥18 years of age at the time of signing the written informed consent and with documented serum potassium levels ≥5.0 mmol/L within 1 year before study enrolment day will be included. Eligible patients will receive SZC treatment and will be followed up for 6 months from enrolment day. The primary objective will be to evaluate the safety of SZC for the management of HK in Chinese patients in terms of adverse events (AEs), serious AEs as well as discontinuation of SZC. The secondary objectives will include understanding the SZC dosage information in terms of its effectiveness and treatment patterns under real-world clinical practice and assessing effectiveness of SZC during the observational period.Ethics and disseminationThis study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (approval number: YJ-JG-YW-2020). All the participating sites have received the ethics approval. Results will be disseminated through national and international presentations and peer-reviewed publications.Trial registration numberNCT05271266.

Spinal cord development is precisely orchestrated by spatiotemporal gene regulatory programs. However, the underlying epigenetic mechanisms remain largely elusive. Here, we profiled single-cell chromatin accessibility landscapes in mouse neural tubes spanning embryonic days 9.5-13.5. We identified neuronal-cell-cluster-specific cis-regulatory elements in neural progenitors and neurons. Furthermore, we applied a novel computational method, eNet, to build enhancer networks by integrating single-cell chromatin accessibility and gene expression data and identify the hub enhancers within enhancer networks. It was experimentally validated in vivo for Atoh1 that knockout of the hub enhancers, but not the non-hub enhancers, markedly decreased Atoh1 expression and reduced dp1/dI1 cells. Together, our work provides insights into the epigenetic regulation of spinal cord development and a proof-of-concept demonstration of enhancer networks as a general mechanism in transcriptional regulation.

Proteinuria is a clinical manifestation of chronic kidney disease that aggravates renal interstitial fibrosis (RIF), in which injury of peritubular microvessels is an important event. However, the changes in peritubular microvessels induced by proteinuria and their molecular mechanisms remain unclear. Thus, we aimed to develop a co-culture microfluidic device that contains renal tubules and peritubular microvessels to create a proteinuria model. We found that protein overload in the renal tubule induced trans-differentiation and apoptosis of endothelial cells (ECs) and pericytes. Moreover, profiling of secreted proteins in this model revealed that a paracrine network between tubules and microvessels was activated in proteinuria-induced microvascular injury. Multiple cytokine receptors in this paracrine network were core-fucosylated. Inhibition of core fucosylation significantly reduced ligand-receptor binding ability and blocked downstream pathways, alleviating trans-differentiation and apoptosis of ECs and pericytes. Furthermore, the protective effect of genetic FUT8 deficiency on proteinuria overload-induced RIF and pericyte-myofibroblast trans-differentiation was validated in FUT8 knockout heterozygous mice. In conclusion, we constructed and used a multiple-unit integrated microfluidic device to uncover the mechanism of proteinuria-induced RIF. Furthermore, FUT8 may serve as a hub-like therapeutic target to alleviate peritubular microvascular injury in RIF. STATEMENT OF SIGNIFICANCE: In this study, we constructed a multiple-unit integrated renal tubule-vascular chip. We reproduced human proteinuria on the chip and found that multiple receptors were modified by FUT8-catalyzed core fucosylation (CF) involved in the cross-talk between renal tubules and peritubular microvessels in proteinuria-induced RIF, and inhibiting the FUT8 of receptors could block the tubule-microvessel paracrine network and reverse the damage of peritubular microvessels and renal interstitial fibrosis. This tubule-vascular chip may provide a prospective platform to facilitate future investigations into the mechanisms of kidney diseases, and target-FUT8 inhibition may be an innovative and potential therapeutic strategy for RIF induced by proteinuria.

Background: Hemodialysis is the main approach for renal replacement therapy in patients with end-stage renal disease (ESRD) in China. The timing of dialysis initiation is one of the key factors influencing patient survival and prognosis. Over the past decade, the relationship between the timing of dialysis initiation and mortality has remained unclear in patients with ESRD in China. Methods: Patients who commenced maintenance hemodialysis from 2009 to 2014 from 24 hemodialysis centers in Mainland China were enrolled in the study (n = 1,674). Patients were divided into 2 groups based on the year they started hemodialysis (patients who started hemodialysis from 2009 to 2011, and patients who started hemodialysis from 2012 to 2014). Analysis of the yearly change in the estimated glomerular filtration rate (eGFR) at the initiation of dialysis was performed for the 2 groups. Meanwhile, the patients were divided into 3 groups based on their eGFR at the initiation of dialysis (8 mL/min/1.73 m2). For these 3 groups, the relationship between the eGFR at the start of dialysis and mortality were analyzed. Results: The average eGFRs were 5.68 and 5.94 mL/min/1.73 m2 for 2009–2011 and 2012–2014, respectively. Compared with the 2009–2011 group, the proportion of patients with diabetes in 2012–2014 increased from 26.7 to 37.7%. The prognosis of patients with different eGFRs at the start of dialysis was analyzed using Kaplan-Meier survival curves. After adjusting for confounding factors through a Cox regression model, no significant difference was demonstrated among the 3 groups (2 was used as the reference, in comparison with 4–8 mL/min/1.73 m2 [p = 0.681] and >8 mL/min/1.73 m2 [p = 0.403]). Conclusion: In Mainland China, the eGFR at the start of dialysis did not change significantly over time from 2008 to 2014 and had no association with the mortality of patients with ESRD.

The use of microfluidics and nanotechnology in bioscience is gaining favor among the next generation of bioscience and clinical researchers, and this field has expanded to include organ-specific applications and modeling. While certain organ-specific microfluidic chips/applications, such as those in the heart and liver, are ubiquitous in the peer-reviewed literature, the kidneys require more focus and attention to drive innovation. This review is a comprehensive overview of kidney microfluidic bio-applications and includes the current challenges and limitations that should be the focus of research efforts. More specifically, previous research efforts focused on glomerular or tubule segments of the kidney, but never both anatomical regions. This is due, in part, to the complexity of reconstituting the kidney complete with all its variable mechanical and biochemical functions. Key words: Kidney, organs and organ systems, microfluidics.

Objective Peritoneal fibrosis (PF) ultimately causes ultrafiltration failure and peritoneal dialysis (PD) termination, but there are few effective therapies for it. Core fucosylation, which is catalyzed by α1,6-fucosyltransferase (Fut8) in mammals, may play a crucial role in PF development. This study aims to assess the effects of inhibiting core fucosylation of epidermal growth factor (EGF) receptor on PF rats. Methods PF rats (established by 4.25% glucose dialysate) were treated with either an adenovirus-Fut8 short hairpin RNA (Fut8shRNA) or adenovirus-control. Masson’s staining and net ultrafiltration were performed at week six. Fut8 level and core fucosylation of EGF receptor and collagen I in the peritoneal membrane were assessed, and EGF signaling was detected, including signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) and their phosphorylation. Monocyte chemoattractant protein-1 (MCP-1) in peritoneal effluent was examined. Results Fut8 was upregulated in PF rats but decreased after Fut8shRNA treatment. EGF and EGF receptor expression was upregulated in PF rats, while core fucosylation of EGF receptor decreased after Fut8shRNA treatment. Masson’s staining results showed an increase in peritoneal thickness in PF rats but a decrease after Fut8shRNA treatment. Fut8shRNA treatment increased net ultrafiltration, reduced the expression of collagen I and MCP-1 compared to PF rats. Fut8shRNA treatment suppressed phosphorylation of STAT3 and NF-κB in the peritoneal membrane of PF rats. Conclusions Fut8shRNA treatment ameliorated the fibrotic changes in PF rats. A potential mechanism may be that Fut8shRNA treatment inactivated EGF signaling pathway by suppressing the phosphorylation of STAT3 and NF-κB.

Renal interstitial fibrosis (RIF) is an incurable pathological lesion in chronic kidney diseases. Pericyte activation is the major pathological characteristic of RIF. Fibroblast and macrophage activation are also involved in RIF. Studies have revealed that core fucosylation (CF), an important post-translational modification of proteins, plays a key role in pericyte activation and RIF by regulating multiple profibrotic signaling pathways as a hub-like target. Here, we reveal that mesenchymal stem cell (MSC)-derived exosomes reside specifically in the injured kidney and deliver microRNA (miR)-34c-5p to reduce cellular activation and RIF by inhibiting CF. Furthermore, we showed that the CD81-epidermal growth factor receptor (EGFR) ligand-receptor complex aids the entry of exosomal miR-34c-5p into pericytes, fibroblasts, and macrophages. Altogether, our findings reveal a novel role of MSC-derived exosomes in inhibiting multicellular activation via CF and provide a potential intervention strategy for renal fibrosis.

The efficacy of Abelmoschus manihot (AM) in treating of chronic kidney disease (CKD) has been confirmed by prior trials. AM is also commonly combined to other medicines among CKD patients in clinic. This trial aimed at evaluating the safety of AM combination application, and further verifying the efficacy of AM in treating various types of CKD.A multicentre, prospective, open-label, single-arm trial SETTING AND PARTICIPANTS: Approximately 2000 CKD patients with proteinuria (≥ 150 mg/d), from 105 centres across China INTERVENTIONS: AM was administered to patients three times per day for 24 weeks: the daily dose was based on age (12 years old: 2.5 g tid; 6∼12 years old: 1.5 g tid; 2∼6 years old: 1 g tid) OUTCOMES: The efficacy outcomes were the change in 24-hour proteinuria and estimated glomerular filtration rate (eGFR) from baseline to week 24. Safety outcomes included adverse events and laboratory tests.2054 CKD patients from 105 centres were enrolled in this trial, with 1843 (89.7%) completing the 24-week follow-up. The participants' median age was 44 years old and 44.6% were female. Compared to baseline, 24-hour proteinuria decreased 471 mg (95% confident interval, 367 to 575, p0.001) at week 24. eGFR did not change significantly relative to baseline with the mean increase as 1.7 ml/min/1.73 mSingle-arm clinical trial and short observation time CONCLUSION: We have provided safety information of AM on various types of CKD in a large trial, especially when combination to medications most commonly prescribed to CKD patients. AM also showed to decrease proteinuria with stable kidney function during follow up. AM is a promising treatment for CKD patients.

Brownfield regeneration (BR) is an important initiative for sustainable land development and the promotion of carbon neutrality. Insufficient stakeholder engagement is one of the main obstacles to the progress of BR. The relationship network formed through continuous interaction among stakeholders ensures the exchange and transfer of information resources. Different structural features of the relationship network may lead to differences in the engagement level of stakeholders. Therefore, based on network embeddedness theory, this study conducts an empirical analysis to explore the impact of the relationship network structure on engagement behavior, for the purpose of increasing the stakeholder engagement level. A theoretical model is developed, in which network centrality, behavioral willingness and involvement climate are selected as the dependent variables of engagement behavior. Using an effective sample of 245 stakeholders involved in BR from ten cities in China, we find that stakeholder network centrality positively affects engagement behavior. There is also a positive relationship between network centrality and behavioral willingness. The behavioral willingness plays an intermediary role between network centrality and engagement behavior, and the involvement climate has a moderating role between behavioral willingness and engagement behavior. Additionally, various strategies can be adopted to promote the engagement level of stakeholders. The findings are useful in establishing a benchmarking framework for BR stakeholder engagement.

Background It is unclear whether short‐term blood pressure variability is associated with renal outcomes in patients with chronic kidney disease. Methods and Results This study analyzed data from participants in the C‐ STRIDE (Chinese Cohort Study of Chronic Kidney Disease) who had chronic kidney disease stages 1 to 4. Short‐term blood pressure variability was measured by calculating the weighted SD (w‐ SD ) of systolic blood pressure ( SBP ). Renal outcomes were defined as dialysis initiation and/or transplantation. Risk factors associated with w‐ SD of SBP were evaluated by linear regression. Associations of short‐term SBP variability with renal outcomes were evaluated by Cox regression. In total, 1421 patients with chronic kidney disease were included in this study (mean age, 49.4±13.6 years; 56.2% men; estimated glomerular filtration rate, 50.5±29.3 mL/min per 1.73 m 2 ; proteinuria, 0.9 [0.3–2.0] g/d). Mean w‐ SD of SBP was 12.6±4.4 mm Hg. w‐ SD of SBP was independently associated with older age, 24‐hour SBP , blood pressure circadian pattern, and angiotensin II receptor blocker treatment. During a median follow‐up of 4.9 years, 237 patients developed renal outcomes (37.01 per 1000 patient‐years). The incidence rate increased across the quartiles of w‐ SD (log‐rank P =0.005). w‐ SD of SBP was associated with an increased risk of renal outcomes, both as a continuous variable (hazard ratio [HR], 1.47; 95% CI, 1.09–1.99) and as a categorical variable (quartile 4 versus quartile 1: HR, 1.60; 95% CI, 1.08–2.36), independent of 24‐hour SBP , daytime SBP , and nighttime SBP . Conclusions Short‐term SBP was independently associated with the risk of dialysis initiation and/or transplantation in patients with chronic kidney disease .

Background: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. Methods: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min −1 ·1.73 m −2 , aged 18–70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t -test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. Results: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (−13.0–24.1) and 11.7 (−2.6–42.9) μmol/L for the test and control groups, respectively ( Z = 2.642, P = 0.008), and the median change in eGFR was −0.2 (−4.3–2.7) and −2.2 (−5.7–0.8) ml·min −1 ·1.73 m −2 , respectively ( Z = −2.408, P = 0.016). There were no significant differences in adverse events between the groups. Conclusions: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. Trial Registration: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102 .

Our previous studies showed that multitarget therapy is superior in efficacy to intravenous cyclophosphamide as an induction treatment for lupus nephritis in Asian populations. We conducted an open label, multicenter study for 18 months as an extension of the prior induction therapy trial in 19 renal centers in China to assess the efficacy and safety of multitarget maintenance therapy in patients who had responded at 24 weeks during the induction phase. Patients who had undergone multitarget induction therapy continued to receive multitarget therapy (tacrolimus, 2–3 mg/d; mycophenolate mofetil, 0.50–0.75 g/d; prednisone, 10 mg/d), and patients who had received intravenous cyclophosphamide induction treatment received azathioprine (2 mg/kg per day) plus prednisone (10 mg/d). We assessed the renal relapse rate during maintenance therapy as the primary outcome. We recruited 116 patients in the multitarget group and 90 patients in the azathioprine group. The multitarget and azathioprine groups had similar cumulative renal relapse rates (5.47% versus 7.62%, respectively; adjusted hazard ratio, 0.82; 95% confidence interval, 0.25 to 2.67; P=0.74), and serum creatinine levels and eGFR remained stable in both groups. The azathioprine group had more adverse events (44.4% versus 16.4% for multitarget therapy; P

Background: Patients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death. Methods: Participants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients’ data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality. Results: In total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094–1.886), age (OR: 1.046, 95% CI: 1.036–1.057), and presence of DN (OR: 1.837, 95% CI: 1.322–2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346–0.989), hemoglobin (OR: 0.974, 95% CI: 0.967–0.981), albumin (OR: 0.939, 95% CI: 0.915–0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070–0.386) were protective factors based on a multivariate analysis. Conclusions: Hemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients. Key words: Hemodialysis; Mortality; Risk Factors

Background IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN. Methods We will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks. Discussion This study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN. Trial registration ClinicalTrials.gov, identifier: NCT02231125. Registered on 30 August 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1774-6) contains supplementary material, which is available to authorized users.

Background FG-4592 (roxadustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (HIF-PHI) promoting coordinated erythropoiesis through the transcription factor HIF. Two Phase 2 studies were conducted in China to explore the safety and efficacy of FG-4592 (USAN name: roxadustat, CDAN name: ), a HIF-PHI, in patients with anemia of chronic kidney disease (CKD), both patients who were dialysis-dependent (DD) and patients who were not dialysis-dependent (NDD). Methods In the NDD study, 91 participants were randomized to low (1.1–1.75 mg/kg) or high (1.50–2.25 mg/kg) FG-4592 starting doses or to placebo. In the DD study, 87 were enrolled to low (1.1–1.8 mg/kg), medium (1.5–2.3 mg/kg) and high (1.7–2.3 mg/kg) starting FG-4592 doses or to continuation of epoetin alfa. In both studies, only oral iron supplementation was allowed. Results In the NDD study, hemoglobin (Hb) increase ≥1 g/dL from baseline was achieved in 80.0% of subjects in the low-dose cohort and 87.1% in the high-dose cohort, versus 23.3% in the placebo arm (P