A total of 269 non-diabetic chronic kidney disease (CKD) patients were enrolled in this study. Among them, 175 patients (65.1%) were assigned to the control group and received conventional therapy with maximally tolerated doses of renin-angiotensin-aldosterone system inhibitors, while 94 patients (34.9%) were assigned to the dapagliflozin group and received oral dapagliflozin 10 mg/day in addition to the conventional therapy. The results showed that the urine protein quantity in the dapagliflozin group was lower than those in the control group at 3, 6, 12, 18, and 24 months of follow-up (all P<0.05), and the blood albumin level was higher than those in the control group at 18 and 24 months of follow-up (all P<0.05). The Kaplan-Meier survival curve analysis results showed that the cumulative renal survival rate of the dapagliflozin group was significantly higher than that of the control group (Log-rank test, χ2=5.078, P=0.024). Multivariable Cox regression analysis results revealed that using dapagliflozin was independently associated with a reduced risk of the composite endpoint in non-diabetic CKD patients ( HR=0.400, 95% CI 0.163-0.983, P=0.046). There was no statistical difference in adverse reactions between the two groups (all P>0.05). It is indicated that dapagliflozin has a renal protective effect independent of hypoglycemic action and good safety.

A total of 269 non-diabetic chronic kidney disease (CKD) patients were enrolled in this study. Among them, 175 patients (65.1%) were assigned to the control group and received conventional therapy with maximally tolerated doses of renin-angiotensin-aldosterone system inhibitors, while 94 patients (34.9%) were assigned to the dapagliflozin group and received oral dapagliflozin 10 mg/day in addition to the conventional therapy. The results showed that the urine protein quantity in the dapagliflozin group was lower than those in the control group at 3, 6, 12, 18, and 24 months of follow-up (all P<0.05), and the blood albumin level was higher than those in the control group at 18 and 24 months of follow-up (all P<0.05). The Kaplan-Meier survival curve analysis results showed that the cumulative renal survival rate of the dapagliflozin group was significantly higher than that of the control group (Log-rank test, χ2=5.078, P=0.024). Multivariable Cox regression analysis results revealed that using dapagliflozin was independently associated with a reduced risk of the composite endpoint in non-diabetic CKD patients ( HR=0.400, 95% CI 0.163-0.983, P=0.046). There was no statistical difference in adverse reactions between the two groups (all P>0.05). It is indicated that dapagliflozin has a renal protective effect independent of hypoglycemic action and good safety.

Objective: To explore the value of baseline geriatric nutritional risk index (GNRI) in evaluating the prognosis of patients with end-stage renal disease (ESRD) who underwent peritoneal dialysis (PD). Methods: The clinical data of patients who underwent PD catheterization and started PD therapy at the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to December 30, 2018 were collected retrospectively. The follow-up endpoint was death or hemodialysis. The follow-up deadline was March 1, 2019. The GNRI cut-off value was determined according to the ROC curve, and the patients were divided into GNRI≤90.5 group and GNRI>90.5 group. The differences of clinical data and laboratory tests were compared between the two groups. Kaplan-Meier survival curves were used to compare the difference in PD rate between the two groups during follow-up, and the factors that affecting patients PD withdrawal were analyzed by Cox regression. Results: The GNRI cut-off value was determined to be 90.5 based on the ROC curve. Until the deadline for follow-up, the drop-out rate of GNRI≤90.5 group was significantly higher than the GNRI>90.5 group (35.88% vs 21.58%, P=0.003). Kaplan-Meier survival curves showed a higher rate of maintaining PD in the GNRI>90.5 group than that in GNRI≤90.5 group during follow-up (P=0.021). Cox univariate regression showed that male, GNRI and serum Alb were protective factors for PD patients, and Scr was a risk factor. After multiple factors correction, male and GNRI were also the protective factors for PD patients. Conclusion As an objective indicator of nutritional evaluation, baseline GNRI can be used as a prognostic indicator for PD patients.

Objective To investigate the incidence situation of metabolic syndrome (MS) in patients with continuous ambulatory peritoneal dialysis (CAPD),and analyze the correlation between MS and prognosis of patients.Methods The patients who received peritoneal dialysis from June 1,2002 to April 30,2018 and followed up regularly were divided into MS group and non-MS group according to the diagnostic criteria of MS.Follow-up was until July 31,2018.The differences of clinical data,metabolic indexes and clinical outcomes between the two groups were compared.The survival rates of the two groups were compared by Kaplan-Meier survival curve,and the risk factors of all-cause death and cardiovascular disease (CVD) death were analyzed by Cox regression analysis.Results A total of 516 patients with CAPD were enrolled in this study,including 340 males (65.9％)and 176 females (34.1％).Their age was (47.29± 12.20) years.The median follow-up time was 20 (9,39) months.According to the diagnostic criteria of MS,the patients were divided into MS group (210 cases,40.7％) and non-MS group (306 cases,59.3％).At baseline,there was no significant difference in age,educational background,duration of peritoneal dialysis,smoking history and drinking history between the two groups (P ＞ 0.05),but the patients in MS group were more exposed to high glucose peritoneal dialysate (P ＜ 0.05).The body mass index (BMI),blood phosphorus,blood glucose,blood potassium,triglyceride,cholesterol and systolic blood pressure in MS group were significantly higher than those in non-MS group (all P ＜ 0.05),and HDL-C level was significantly lower in MS group than in non-MS group (P ＜ 0.05).There were no significant differences in other indicators between the two groups (P ＞ 0.05).Kaplan-Meier survival curve showed that the cumulative survival rate in MS group was significantly lower than that in non-MS group,and the difference was statistically significant (Log-rank x2=14.87,P ＜ 0.001).If CVD death was taken as the end event,the cumulative survival rate in the non-MS group was significantly higher than that in the MS group (Log-rank x2=14.49,P ＜ 0.001).Multivariate Cox regression analysis showed that MS and high 4 h dialysate creatinine/serum creatinine ratio (4hD/Pcr) were independent risk factor for all-cause death (HR=1.982,95％CI 1.240-3.168,P=0.004;HR=3.855,95％CI 1.306-11.381,P=0.015) and CVD death (HR=2.499,95％CI 1.444-4.324,P=0.001;HR=5.799,95％ CI 1.658-20.278,P=0.006) in patients with CAPD.Conclusion The prevalence of MS in patients with CAPD is high,and MS and high 4hD/Pcr are independent risk factor for all-cause and CVD death in CAPD patients.They can be used as valuable indicators to predict the treatment outcomes and long-term prognosis of patients with CAPD.

Objective To evaluate the clinico-pathologic presentations and prognosis in the very elderly patients undergoing renal biopsy.Methods The patients who underwent renal biopsy in Nephrology Center of the First Affiliated Hospital of Zhengzhou University were screened from May 2012 to March 2016.All patients were divided into observation group (aged ≥80 years) and control group (aged 65-70 years).The clinico-pathological classifications and prognosis were compared between the two groups.Results Primary glomerulopathy was the most frequent pathologic diagnosis in observation and control groups[20(60.6％) and 64(64.0％),respectively,P=0.726].Among primary glomerulopathy,membranous nephropathy was the most frequent histopathological type[10(50.0％) and 40 (62.5％)] in observation and control groups,respectively,(P =0.320).Among secondary glomerulopathy,the number of patients in observation group were 10 cases (30.3％) and were 13 cases (13.0％) in control group (t=5.194,P＜0.05),with no significant differences between the two groups in amyloid degeneration,ANCA-associated vasculitis,HBV-associated Glomerulonephritis,and nephritis of Schonlein-Henoch purpura.In the very elderly patients with nephrotic syndrome,glomerular minimal change was the most common histological type [7 (30.4％)],followed by membranous nephropathy[6 (26.1％)].Furthermore,there were no side effects of perinephric hematoma,gross hematuria,arteriovenous fistula or other complications.Conclusions The pathological types distribution of patients aged ≥ 80 versus 65-70 years is different.And the renal biopsy is relatively safe and has an important role for the very elderly patients.

Objective To investigate the association of red cell distribution width (RDW) with all-cause and cardiovascular disease (CVD)-related mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).Methods A retrospective analysis was performed on 207 patients who initiated CAPD for more than 3 months between July 2005 and March 2016 in the First Hospital Affiliated to Zhengzhou University.Baseline data on demographic,clinical and biochemical variables as well as comorbidities were obtained;medications and clinic outcomes were recorded.According to receiver operator characteristic curve (ROC) analysis,patients were divided into high RDW (RDW ＞ 15.1％) and low RDW (RDW≤ 15.1％) groups.The data of two groups were compared and Spearman's correlation analysis was used to explore the association of RDW with clinical and biochemical parameters.Survival curves were calculated using Kaplan-Meier method.Cox regression model was employed to analyze risk factors of all-cause and CVD-related mortality.Results In this study,207 CAPD patients were enrolled.The overall median survival time was 80 months.And the median survival time of high RDW group (68 patients) and low RDW group (139 patients) were 59 months and 96 months,respectively.There were statistical differences in diastole pressure,hemoglobin,hematocrit,serum albumin,intact parathyroid hormone (iPTH),eGFR,cholesterol,lipoprotein a,4-hour dialysate-to-plasma ratio for creatinine (4hD/Pcr),total Ccr (P ＜ 0.05,respectively);the two groups also varied in the proportion of chronic obstructive pulmonary disease,cardiovascular disease and hyperlipidemia,as well as in the use of iron supplements,angiotensin-converting enzyme (ACE) inhibitors or angiotensin Ⅱ receptor blockers (ARB),and beta-receptor blockers (P＜0.05,respectively).Cardiovascular event was a leading cause of mortality.Kaplan-Meier survival curves showed that the high RDW group had higher all-cause and CVD-related mortality compared with the low RDW group (P ＜ 0.01).The 1-year,3-year,and 5-year patient survivals of the high RDW and low RDW group were 87.97％ vs 97.01％,58.02％ vs 81.53％,and 41.62％ vs 67.96％,respectively,demonstrating significant differences (P=0.001).Multivariate Cox regression analysis showed that high RDW was independent risk factor for all-cause mortality (HR=1.212,95％CI:1.007-1.458,P=0.042) and CVD-related mortality (HR=1.697,95％ CI:1.030-2.795,P=0.038).Conclusion RDW is associated with mortality risks in CAPD patients and can be stratified as a valuable indicator for the risk of death.

Objective To observe the expression of ChemR23 induced by Angiotensin Ⅱ (Ang Ⅱ) in podocyte and its role in renal injury.Methods Conditionally immortalized mice podocytes were cultured in vitro.Immunofluorescence was used to observe the sub-cellular location of ChemR23.The expressions of ChemR23,Nephrin and Podocin stimulated by different concentrations of Ang Ⅱ were detected by qRT-PCR and Western blotting.Lentivirus targeting ChemR23 was used.The expressions of Nephrin and Podocin and the phosphorylation state of NF-κB P65 were detected by Western Blot.The inhibitor of NF-κB P65 was added to the cultural medium for 2 h before Ang Ⅱ stimulation.The effect of NF-κB P65 inhibitor on Ang Ⅱ-induced expression of Nephrin and Podocin was detected by Western Blot.Results It is showed that ChemR23 was located in cytosol and membrane.Compared with the normal control,the expression of ChemR23 was significantly increased by Ang Ⅱ in mRNA and protein level,while the expressions of Nephrin and Podocin were decreased (P ＜ 0.05).When using Lentivirus vector to interfere the expression of ChemR23,Ang Ⅱ-repressed expressions of Nephrin and Podocin were restored (P ＜ 0.05).Western Blot showed the level of phosphorylated NF-κB P65 was significantly increased by Ang Ⅱ stimulation (P ＜ 0.05),which could be inhibited by interfering the expression of ChemR23.When adding the NF-κB P65 inhibitor,the low expression of Nephrin and Podocin induced by Ang Ⅱ stimulation was restored (P＜0.05).Conclusions Ang Ⅱ can induce ChemR23 expression,which activates NF-κB P65 signaling pathway,and then inhibits the expressions of Nephrin and Podocin.Targeting ChemR23 is a potential way to alleviate podocyte injury caused by Ang Ⅱ.

Objective To investigate whether the JAK2/STAT3 signaling pathway is involved in the epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells in uremic peritoneal dialysis (PD) rats.Methods A total of 48 male Sprague-Dawley (SD) rats were randomly separated into six groups:normal control group (NC group,n=8),sham group (n=8),uremic group (n=8),PD group (n=8),S3I-201 control group (n=8) and S3I-201 group (n=8).Uremic model generated by 5/6 nephrectomy surgery in rats was established.The rats of PD group,S3I-201 control group and S3I-201 group received daily infusion of 4.25％ glucose-based peritoneal dialysate fluid (3 ml/100 g) from PD catheters for 28 days.Rats of S3I-201 group were injected with STAT3 inhibitor S3I-201 (2.5 mg/kg) solution from the catheters every other day;the same dose of the solvent of S3I-201 was simultaneously given to S3I-201 control group rats.After PD for 28 days,peritoneal function,pathologic changes,and microvessel density (MVD) were evaluated.Creatinine,urea nitrogen and interleukin-6 (IL-6) concentration in blood and dialysate,and protein and mRNA levels of phospho-JAK2 (p-JAK2),phospho-STAT3 (p-STAT3),E-cadherin,alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor (VEGF) in peritoneum were determined.Results Uremia and peritoneal dialysate could aggravate the peritoneal function and elevate peritoneal thickness and MVD.They could also increased the concentration of IL-6 in blood and dialysate and the expression levels of α-SMA,VEGF,p-JAK2 and p-STAT3 in peritoneum,while lowering E-cadherin expression in peritoneum.These manifestations were even more remarkable in PD group compared to those in uremic group.There was no statistical difference between the S3I-201 control group and the PD group as regards all the index (all P ＞ 0.05).Compared with the S3I-201 control group,the rats treated with S3I-201 showed better peritoneal function.S3I-201 could reduce peritoneal thickness (P＜0.05),MVD (P＜0.05),the concentration of IL-6 in blood and dialysate,the mRNA and protein expression of α-SMA,VEGF,p-JAK2 and p-STAT3 (all P ＜ 0.05),while enhance the mRNA and protein expression of E-cadherin (all P ＜ 0.05).Conclusions After STAT3 is inhibited,the peritoneal thickness,MVD and IL-6 concentration in PD rats are decreased,and EMT is also inhibited,while peritoneal function is improved.The JAK2/STAT3 signaling pathway may thus be involved in the process of EMT of peritoneum in uremic peritoneal dialysis rats by regulating the expression of IL-6.

Objective To observe the expression of NOD2 and epithelial-mesenchymal transition (EMT) related proteins in podocytes in high glucose environment,and explore the molecular mechanism of NOD2 involved in EMT.Methods The human glomerular podocytes were the subjects of study.α-SMA and Nephrin expressions were detected by immunofluorescence;the mRNA and protein expressions of NOD2,Snail and EMT related proteins (α-SMA,Desmin,E-cadherin,Nephrin) were detected by real-time fluorescence quantitative PCR and Western blotting.The podocytes were stimulated by high-glucose after shRNA interfering the of NOD2 expression,and the expressions of Snail and subsequent EMT-related proteins were detected by Western blotting.Prior to the activation of NOD2 by muramyl dipeptide (MDP),shRNA was used to interfere with the expression of Snail.E-cadherin,Nephrin,Desmin,and α-SMA were detected by Western blotting.Results After 24 hours of high glucose stimulation,PCR and Western blotting results showed that the expressions of NOD2 and Snail were significantly increased;the expressions of epithelial phenotype proteins E-cadherin and Nephrin were down-regulated;and the expressions of interstitial phenotype proteins Desmin and α-SMA were increased (all P ＜ 0.05);while there was no significant change in the hypertonic control group.After interference with NOD2,the abnormal expression of Snail and EMT related proteins were all recovered.After interference with Snail expression,Compared with the MDP group,the protein expressions of E-cadherin and Nephrin were significantly increased (all P ＜ 0.05);the expressions of Desmin and α-SMA were significantly decreased.Conclusions High glucose can induce NOD2 expression in podocytes,and promote podocyte epithelial-mesenchymal transition by upregulating Snail expression.Gene intervention targeting the NOD2/Snail/EMT pathway can reduce high-glucose-induced podocyte injury and may provide new ideas for the treatment of diabetic nephropathy.