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Summary Observational studies on dietary or circulating magnesium and risk of cardiovascular disease (CVD) in Chronic Kidney Disease (CKD) stage 1–4 have reported no-to-modest inverse associations. 24 h Urinary magnesium concentration (24 h UMg), an indicator of intestinal magnesium absorption, may provide better insight into the connection of CKD progression. We examined 3179 participants aged 18–74 years with CKD stage 1–4 in the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) study, a prospective population-based cohort study. Data were analysed using Spearman rank-order correlation coefficients for all comparisons. We also performed a time-to-event analysis of the data using the Kaplan–Meier survival model, Cox proportional hazard model and competing risk Fine and Gray subdistribution hazard model. During a median follow-up of 4.19 years (interquartile range, 3.43–5.09 years), when modelling end-stage renal disease (ESRD), CVD and death, 24 h UMg was associated with risk of CVD (HR, 1.612 (95% CI, 1.056–2.460)), while no significant association with ESRD and death endpoints could be detected. 24 h UMg risk variants display a modest association with CVD in CKD stage 1–4 patients. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 ).

Objectives: The primary objective of the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study is to explore potential predictors and their effects on patient survival, technique survival, and the occurrence of infectious and noninfectious complications. Design: The PDTAP study is a national-level cohort study in China. A newly developed PD telemedicine application provided a unique and convenient way to collect multicenter, structured data across units. Setting: The PDTAP study was underway in 27 hospitals from 14 provinces located at 7 geographical regions (northwest, northeast, north, central, southwest, southeast, and south) in China. Participants: Our study aims to enroll at least 7000 adult patients with end-stage renal disease receiving PD. Methods: Approval has been obtained through the ethics committees of all hospitals. All participants signed the informed consent form after the center had received ethics board approval in accordance with the Declaration of Helsinki. Main outcome measures: Patient survival, technique survival, hospitalization, and the occurrence of infectious and noninfectious complications. Conclusions: The PDTAP study aims to explore potential predictors and their effects on patient survival, technique survival, and infectious and noninfectious complications using a newly developed PD telemedicine system to collect multicenter, structured data in real-world practice. Substantial and transformable findings in relation to PD practices were expected. This study also developed a national-level infrastructure for further collaboration and ancillary investigation.

Background For most women who have had a previous cesarean section, vaginal birth after cesarean section (VBAC) is a reasonable and safe choice, but which will increase the risk of adverse outcomes such as uterine rupture. In order to reduce the risk, we evaluated the factors that may affect VBAC and and established a model for predicting the success rate of trial of the labor after cesarean section (TOLAC). Methods All patients who gave birth at Northwest Women’s and Children’s Hospital from January 2016 to December 2018, had a history of cesarean section and voluntarily chose the TOLAC were recruited. Among them, 80% of the population was randomly assigned to the training set, while the remaining 20% were assigned to the external validation set. In the training set, univariate and multivariate logistic regression models were used to identify indicators related to successful TOLAC. A nomogram was constructed based on the results of multiple logistic regression analysis, and the selected variables included in the nomogram were used to predict the probability of successfully obtaining TOLAC. The area under the receiver operating characteristic curve was used to judge the predictive ability of the model. Results A total of 778 pregnant women were included in this study. Among them, 595 (76.48%) successfully underwent TOLAC, whereas 183 (23.52%) failed and switched to cesarean section. In multi-factor logistic regression, parity = 1, pre-pregnancy BMI 2, cervical score ≥ 5, a history of previous vaginal delivery and neonatal birthweight Conclusion The TOLAC was useful to reducing the cesarean section rate. Being primiparous, not overweight or obese, having a cervical score ≥ 5, a history of previous vaginal delivery or neonatal birthweight

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 and Aims Focal segmental glomerulosclerosis (FSGS) mediates the kidney podocyte dysfunction and leads to chronic renal diseases worldwide. Current treatment options are limited, owing to the poor understanding of the metabolic pathologic variations and regeneration of FSGS. Mesenchymal stem cells (MSC) offer the better insights to prevent renal injury and could promote the recovery of renal structure and function through complex mechanisms. Due to the safe, feasible, and therapeutic features, we first designed to investigate the role of human umbilical mesenchymal stem cells (HUMSCs) on FSGS mice and explored the potential serum metabolomic variations. Method Nephropathy was induced by adriamycin (ADR) in male Balb/C mice to study FSGS via intravenous administration. 2*106 HUMSCs are provided to treat FSGS model for 3 times. Renal function was measured by urine protein, serum urea nitrogen (BUN) and serum creatinine (SCr) in the study. Serum metabolic profiles from three groups of Balb/C mice were analysed using ultra- performance liquid chromatography coupled with a triple quadrupole-linear ion trap mass spectrometer and a novel mass spectrometry (UPLC-MS/MS) data collection technique. Results The concentrations of SCr and BUN were apparently decreased after HUMSCs injection for three times compared with the FSGS model and body weight from HUMSCs group was improved significantly. A total of 532 differential metabolites were identified between FSGS group and the normal control group. Bile acid dysregulation and valine/leucine/ isoleucine metabolism pathway, especially, N-acetylvaline and L-valine, were positively associated to ADR-induced FSGS. A panel of identified specific metabolites (pyrrole-2- carboxylic acid, urocanic acid and 6-hydroxynicotinic acid) as well as valine/leucine/isoleucine metabolism pathway rather than bile acid metabolism were related to the renal repair after HUMSCs treatment. Conclusion The administration of HUMSCs in FSGS induced ADR provides the promising protection owing to the improvement of metabolomics. Figure 2. The distribution of DiR-HUMSCs in vivo. Figure 3. Kidney pathology using periodic acid-Schiff (PAS) and Masson staining. Figure 4. Metabolome profiling analysis and Venn diagram for comparisons of numbers from each group. Figure 5. Metabolic pathway analysis results from FSGS + Saline and FSGS + HUMSCs groups. Figure S1. The quality control (QC) of serum metabolomics was designed and performed as follows. Figure S2. Metabolic pathway analysis results from FSGS + Saline and Normal + Saline groups. Figure S3. Metabolic pathway analysis results from FSGS + HUMSCs and Normal + Saline groups.

Supplementary_Table_1 for The Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study: Design and methods by Tiantian Ma, Zhikai Yang, Shaomei Li, Huaying Pei, Jinghong Zhao, Yi Li, Zibo Xiong, Yumei Liao, Zhanzheng Zhao, Jing Xiao, Ying Li, Qiongzhen Lin, Zhaoxia Zheng, Liping Duan, Gang Fu, Shanshan Guo, Wenbo Hu, Yulin Li, Fuyun Sun, Nan Zhao, Qin Wang, Tianrong Ji, Beiru Zhang, Rui Yu, Li Hao, Guiling Liu, Li Zuo, Huiping Zhao, Caili Wang, Lirong Deng, Hongyu Chen, Li Li, Yulan Shen, Yong Zhang, Lihua Wang, Yan Yan, Zhigang Ma, Yingping Li, Xianchao Zhang, Xuejian Wang, Yirong Liu, Xinying Gao, Zhonggao Xu, Li Zhang, Shutong Du, Cui Zhao, Xiaoli Chen, Hongyi Li, Yingli Yue, Shanshan Chen, Yingchun Ma, Yuanyuan Wei, Jingwei Zhou, Jie Lv, Yingdong Zheng, Sainan Zhu, Minghui Zhao and Jie Dong in Peritoneal Dialysis International

Background The timing of when to initiate dialysis for progressive chronic kidney disease (CKD) patients has not been well established. There has been a strong trend for early dialysis initiation for these patients over the past decades. However, the perceived survival advantage of early dialysis has been questioned by a series of recent observational studies. The only randomized controlled trial (RCT) research on this issue found the all-cause mortality, comorbidities, and quality of life showed no difference between early and late dialysis starters. To better understand optimal timing for dialysis initiation, our research will evaluate the efficacy and safety of deferred dialysis initiation in a large Chinese population. Methods The trial adopts a multicenter, cluster randomized, single-blind (outcomes assessor), and endpoint-driven design. Eligible participants are 18–80 years old, in stable CKD stages 4–5 (eGFR > 7 ml/min /1.73 m2), and with good heart function (NYHA grade I or II). Participants will be randomized into a routine or deferred dialysis group. The reference eGFR at initiating dialysis for asymptomatic patients is 7 ml/min /1.73 m2 (routine dialysis group) and 5 ml/min/1.73 m2 or less (deferred dialysis group) in each group. The primary endpoint will be the difference of all-cause mortality and acute nonfatal cerebro-cardiovascular events between the two groups. The secondary outcomes include hospitalization rate and other safety indices. The primary and secondary outcomes will be analyzed by appropriate statistical methods. Discussion This study protocol represents a large, cluster randomized study evaluating deferred and routine dialysis intervention for an advanced CKD population. The reference eGFR to initiate dialysis for both treatment groups is targeted at less than 7 ml/min/1.73m2. With this design, we aim to eliminate lead-time and survivor bias and avoid selection bias and confounding factors. We acknowledge that the study has limitations. Even so, given the low-targeted eGFR values of both arms, this study still has potential economic, health, and scientific implications. This research is unique in that such a low targeted eGFR value has never been studied in a clinical trial. Trial registration The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT02423655). The date of registration was April 22, 2015.

The aim of this study is to investigate the role of Hepatitis B virus x (HBx) in the growth and secretion of human placental trophoblasts. Firstly, placenta tissues were collected from pregnant HBV carriers with various viral loads. The results of immunohistochemical technique showed that the HBx protein and pEGFR protein levels were both markedly increased with the viral load elevation. Then, a placental trophoblast cell strain (JEG-3-HBx), which stably expressed HBx mRNA and protein, was established with the pcDNA-HBx transfection followed by the G418 selection. The JEG-3-HBx strain displayed distinct activation of the EGFR/AKT pathway, a lower level of cell apoptosis, and higher secretion levels of placental hormones, including human chorionic gonadotropin (hCG), progesterone, estrogen and β-endorphin. Subsequently, HBx siRNA was used to silence the HBx gene in the JEG-3-HBx strain. Our data showed that the HBx siRNA transfection markedly suppressed the activation of the EGFR/AKT pathway, promoted cell apoptosis, and reduced the secretion of the placental hormones. Finally, EGF was applied to simulate the JEG-3-HBx strain with or without the HBx siRNA transfection. EGF treatment counteracted the reduction of cell apoptosis and the suppression of hormone secretion caused by HBx siRNA in the cell strain. In conclusion, the pEGFR protein was robustly upregulated in HBx-infected human placenta tissues and trophoblast cells. HBx reduces cell apoptosis and promotes the secretion of placental hormones in human placental trophoblast cells via activation of the EGFR/Akt pathway.

Crescentic IgA nephropathy (IgAN), defined as >50% crescentic glomeruli on kidney biopsy, is one of the most common causes of rapidly progressive GN. However, few studies have characterized this condition. To identify risk factors and develop a prediction model, we assessed data from patients ≥ 14 years old with crescentic IgAN who were followed ≥ 12 months. The discovery cohort comprised 52 patients from one kidney center, and the validation cohort comprised 61 patients from multiple centers. At biopsy, the mean serum creatinine (SCr) level ± SD was 4.3 ± 3.4 mg/dl, and the mean percentage of crescents was 66.4%± 15.8%. The kidney survival rates at years 1, 3, and 5 after biopsy were 57.4%± 4.7%, 45.8%± 5.1%, and 30.4%± 6.6%, respectively. Multivariate Cox regression revealed initial SCr as the only independent risk factor for ESRD (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.10 to 1.57; P=0.002). Notably, the percentage of crescents did not associate independently with ESRD. Logistic regression showed that the risk of ESRD at 1 year after biopsy increased rapidly at SCr>2.7 mg/dl and reached 90% at SCr>6.8 mg/dl (specificity=98.5%, sensitivity=64.6% for combined cohorts). In both cohorts, patients with SCr>6.8 mg/dl were less likely to recover from dialysis. Analyses in additional cohorts revealed a similar association between initial SCr and ESRD in patients with antiglomerular basement membrane disease but not ANCA-associated systemic vasculitis. In conclusion, crescentic IgAN has a poor prognosis, and initial SCr concentration may predict kidney failure in patients with this disease.

The efficacy of urinary biomarkers for predicting adverse clinical outcomes in drug-induced chronic tubulointerstitial nephritis (D-CTIN) has not been well described.A total of 54 patients with D-CTIN were prospectively followed-up in this study. The urinary excretion of α1-microglobulin and transforming growth factor-β1 and the activity of urinary N-acetyl-β-D-glucosaminidase (NAG) and matrix metalloproteinases (MMPs) 2 and 9 at baseline were measured. Changes in the estimated glomerular filtration rate (GFR) over a period of 11 to 54 months (median, 38 months) of follow-up were recorded. The efficacy of urinary biomarkers for differentiating patients with various outcomes was tested. Ten patients with IgA nephropathy and 20 healthy volunteers were enrolled as controls.The areas under the receiver operating characteristic curve for urinary NAG, MMP-9, MMP-2 and α1-microglobulin for predicting deterioration of the estimated GFR were 0.879, 0.867, 0.735 and 0.709, respectively (P0.05 for all). Partial regression coefficient results demonstrated that urinary NAG (P = 0.02), MMP-2 (P = 0.046) and MMP-9 (P = 0.041) were inversely correlated with the rate of GFR decline.Urinary NAG, MMP-2 and MMP-9 may be considered as possible candidates for forecasting the progression rate of D-CTIN.

Background/Aims: This study explored the correlation between hypertension and non-muscle myosin heavy chain 9 (MYH9) gene polymorphisms in Chinese chronic kidney disease (CKD) patients. Methods: This case-control study included 301 patients with CKD and 293 healthy controls. The E1 haplotype single nucleotide polymorphisms (SNPs) rs3752462 and rs4821480 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The association between MYH9 polymorphisms and high systolic blood pressure (SBP ≥ 140 mmHg) susceptibility in CKD patients was analysed. Results: The cases and controls had similar genotype and allele distributions at rs3752462 and rs4821480. No GG genotype at rs4821480 was observed. Patients with SBP < 140 mmHg were more likely to have the CC genotype (17.1%) than patients with SBP ≥ 140 mmHg (4.3%) (P = 0.001). Creatinine clearance (OR = 0.99, 95% CI = 0.98-0.10, P = 0.01) was associated with SBP in patients with CKD. The risk of SBP ≥ 140 mmHg was 0.24-fold greater among patients with the CC genotype than among patients with the TT genotype (P = 0.002). Conclusion: The rs3752462 polymorphism of MYH9 is associated with SBP in patients with CKD. The T allele in the dominant model was associated with an elevated risk for high SBP.

We created a cross-species display system that allows the display of the same antibody libraries on both prokaryotic phage and eukaryotic yeast without the need for molecular cloning. Using this cross-display system, a large, diverse library can be constructed once and subsequently used for display and selection in both phage and yeast systems. In this article, we performed the parallel phage and yeast selection of an antibody maturation library using this cross-display platform. This parallel selection allowed us to isolate more unique hits than single-species selection, with 162 unique clones from phage and 107 unique clones from yeast. In addition, we were able to shuttle yeast hits back to Escherichia coli cells for affinity characterization at a higher throughput.