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Objective:To investigate the association of monocyte to lymphocyte ratio (MLR) with all-cause mortality and cardiovascular disease (CVD) mortality in patients with continuous ambulatory peritoneal dialysis (CAPD).Methods:It was a retrospective cohort study. The clinical data of 495 incident CAPD patients in the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to December 31, 2019 were retrospectively analyzed. The optimal cut-off value of baseline MLR was determined by the receiver operating characteristic (ROC) curve for predicting all-cause death in the first year of CAPD, and then the patients were divided into high MLR group and low MLR group. The differences of clinical data and laboratory tests were compared between the two groups. The endpoint events were death (all-cause death and CVD death), conversion to hemodialysis, conversion to kidney transplantation, or follow-up until March 31, 2020. The survival curve was drawn by the Kaplan-Meier method, and the Log-rank test was used to compare the survival difference between the two groups. A Cox regression model was established to analyze the relevant factors of all-cause mortality and CVD mortality in CAPD patients.Results:The study included 495 patients, with age of (43.79±12.16) years and 308 (62.22%) males. The median age of dialysis was 17(10, 30) months. By the end of follow-up, 61(12.32%) of 495 patients had died, 51(10.51%) had been converted to hemodialysis, and 28(5.66%) had been converted to kidney transplantation. Of the 61 patients who died, 36(59.02%) died of cardiovascular events. ROC curve analysis results showed that the optimal cut-off value was 38.24%, so there were 246 cases in the high MLR group (MLR>38.24%) and 249 cases in the low MLR group (MLR≤38.24%). The all-cause mortality rates were 6.83% in the low MLR group and 17.89% in the high MLR group, and the CVD mortality rates were 3.21% in the low MLR group and 11.38% in the high MLR group, respectively. The Kaplan-Meier survival curve showed that the survival rate of the low MLR group was significantly higher than that of the high MLR group (all-cause mortality, Log-rank χ2=18.369, P<0.001; CVD mortality, Log-rank χ2=16.142, P<0.001). Using all-cause death as the end event, the 1-year, 3-year and 5-year cumulative survival rates were 99.5%, 89.4% and 79.9%, respectively, with a median survival time of 64 months in the low MLR group. The 1-year, 3-year and 5-year cumulative survival rates were 95.0%, 68.3% and 49.6%, respectively, with a median survival time of 54 months in the high MLR group. Using CVD death as the end event, the 1-year, 3-year and 5-year cumulative survival rates were 99.5%, 95.2% and 91.2%, respectively, with a median survival time of 69 months in the low MLR group. The 1-year, 3-year, and 5-year cumulative survival rates were 97.8%, 78.6%, and 60.8%, respectively, with a median survival time of 60 months in the high MLR group. Multivariate Cox regression analysis showed that MLR was independently associated with all-cause mortality ( HR=2.744, 95% CI 1.484-5.075, P=0.001) and CVD death ( HR=3.249, 95% CI 1.418- 7.443, P=0.005) in CAPD patients. According to the competing risk model analysis, MLR was still independently associated with all-cause mortality and CVD mortality in CAPD patients. Conclusion:MLR is associated with all-cause mortality and CVD mortality in CAPD patients, and can be used as a valuable indicator for judging the prognosis of CAPD patients.
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Objective:To investigate changes in serum C3d and C5b-9 levels in elderly patients with idiopathic membranous nephropathy(IMN)and their correlations with prognosis.Methods:Two hundred thirty-one elderly patients with IMN and 96 non-elderly patients with IMN confirmed by kidney biopsy at the First Affiliated Hospital of Zhengzhou University from January 2015 to May 2017 were enrolled.During the same period, 118 healthy individuals receiving health checkups were included as controls.Patients were divided into the low C3d group( n=112)and the high C3d group( n=113)according to the median level of serum C3d.Serum C3d and C5b-9 levels were measured by enzyme-linked immunosorbent assays. Results:Serum C3d and C5b-9 levels in elderly IMN patients were 0.23(0.15, 0.45)mg/L and 0.28(0.20, 1.23)mg/L, respectively, which were higher than those in healthy controls[0.18(0.13, 0.22)mg/L, 0.22(0.16, 0.26)mg/L, respectively]( Z=-4.261 and -6.213, P<0.001). Serum C3d levels in elderly and non-elderly IMN patients were correlated negatively with the estimated glomerular filtration rate( r=-0.155 and -0.426, P=0.019 and 0.000), but positively with serum creatinine, anti-phospholipase A2 receptor(PLA2R)antibody levels and 24 h urinary protein( r=0.184, 0.326, 0.407, 0.321 and 0.145, P=0.005, 0.001, 0.000, 0.001 and 0.027). Kaplan-Meier survival analysis showed that the cumulative renal survival rate in elderly IMN patients was lower in the high C3d group than in the low C3d group(47.8% vs.70.8%, Log Rank χ2=7.399, P=0.007). Multivariate Cox regression analysis showed that high C3d levels were an independent risk factor for poor renal outcomes in elderly IMN patients( HR=2.288, 95% CI: 1.082-4.839, P=0.030). Conclusions:High serum C3d levels are associated with increases in urinary protein excretion and anti-PLA2R antibody levels, renal function decline, and poor renal outcomes in elderly IMN patients.
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Objective:To detect serum level of complement factor B (CFB), and to explore its correlations with clinical parameters and prognosis in children with primary IgA nephropathy (IgAN).Methods:A total of 204 children with primary IgAN confirmed by kidney biopsy in the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University from December 2014 to April 2017 were included in IgAN group.During the same period, 84 healthy children were included in healthy control group.Their mean age was (11.0±3.5) years and (10.9±3.2) years, respectively.Patients in IgAN group were divided into low CFB group (102 cases) and high CFB group (102 cases) according to the medium serum level of CFB measured by enzyme-linked immunosorbent assay. Spearman′ s coefficient was employed to analyze correlation amongst various parameters.Multivariable-adjusted Cox proportional ha-zards models were used to evaluate the relationship between serum CFB level and prognosis in children with IgAN. Results:Serum CFB levels were significantly higher in IgAN group than that in healthy control group [290.9 (186.2-453.9) mg/L vs.218.9 (155.0-321.3) mg/L, Z=-3.372, P=0.001]. Serum levels of CFB were negatively correlated with serum albumin ( r=-0.388, P<0.001) and estimated glomerular filtration rate ( r=-0.416, P<0.001), but positively correlated with serum creatinine ( r=0.305, P<0.001) and 24 h urinary protein ( r=0.456, P<0.001) in IgAN group.The incidences of crescents (C1-2) (70.6% vs.29.4%, χ2=34.588, P<0.001) and C 3 deposition (+ + -+ + + ) (63.7% vs.44.1%, χ2=7.892, P=0.005) were significantly higher in high CFB group than those in low CFB group. Kaplan- Meier analysis showed that high CFB levels predicted worse renal outcome in pediatric IgAN patients ( χ2=17.509, P<0.001). Multivariate Cox regression analysis showed that the high CFB level was the independent risk factor for the poor renal outcome ( HR=2.517, 95% CI: 1.284-4.932, P=0.007). Conclusions:High serum levels of CFB are associated with decreased renal function, increased urinary protein excretion, crescentic formation and poor renal outcome in pediatric IgAN patients.
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Objective:To develop and validate a predictive model for the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus.Methods:A retrospective study with patients with type 2 diabetes who underwent renal biopsy in the First Affiliated Hospital of Zhengzhou University from February 2012 to January 2015 was conducted. The dataset was randomly split into development (70.0%) and validation (30.0%) cohorts. Baseline predictors for model development was selected by using univariable and multivariable logistic regression. The model's performance in the two cohorts, including discrimination and calibration, was evaluated by the C-statistic, calibration curve and the P value of the Hosmer-Lemeshow test. Results:Among the 931 patients with type 2 diabetes, 478 cases (51.3%) diagnosed as DN alone, 214 cases (23.0%) as NDRD alone and 239 cases (25.7%) as DN plus superimposed NDRD (MIX). Among NDRD and MIX patients, membranous nephropathy was the most common pathological type, followed by IgA nephropathy. The variables selected in the final predictive model were age, duration of diabetes, diabetic retinopathy, systolic blood pressure, hemoglobin, fasting blood glucose, glycosylated hemoglobin, cystatin C. The model performed well with good discrimination and calibration. The C-statistics were 0.913(95% CI 0.892-0.935) in the derivation cohort and 0.897(95% CI 0.876-0.919) in the validation cohort. The model had the best P value of 0.934 of the Hosmer-Lemeshow test. Conclusions:A simple predictive model with high accuracy is constructed for predicting the presence of NDRD and MIX for type 2 diabetic patients. The nomogram can be used as a decision support tool to provide a non-invasive method for differential diagnosis of DN and NDRD, which may help clinicians assess the risk-benefit ratio of kidney biopsy for type 2 diabetic patients with renal impairment.
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Objective:To compare the prognosis of hemodialysis (HD) and peritoneal dialysis (PD) in end-stage renal disease (ESRD) patients without diabetes mellitus and identify related influencing factors.Methods:Patients who started hemodialysis with an arteriovenous graft or fistula or PD in the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to February 1,2019 were included. They were followed up until May 1, 2019. The patients were divided into HD group and PD group according to the initial dialysis modality. Kaplan-Meier method was used to obtain survival curves, the Cox regression model was used to evaluate influence factors for survival rates, and the inverse probability of treatment weighting (IPTW) was used to eliminate influence of the confounders in the groups.Results:There were 371 patients with maintenance dialysis enrolled in this study, including 113 cases (30.5%) in HD group and 258 cases (69.5%) in PD group. At baseline, the scores of standard mean difference ( SMD) in age, body mass index (BMI), combined with cerebrovascular disease, Charlson comorbidity index (CCI), blood potassium, plasma albumin and hemoglobin between the two groups were greater than 0.1. The score of SMD decreased after IPTW, and the most data were less than 0.1, which meant that the balance had been reached between the two groups. The Kaplan-Meier survival curve showed that the cumulative survival rates had no significant difference for all-cause death before using IPTW between the two groups (Log-rank χ2=0.094, P=0.759). After adjusting for confounders with IPTW, the Kaplan-Meier survival curve showed that the cumulative survival rates still had no significant difference for all-cause death between the two groups (Log-rank χ2=2.090, P=0.150). Univariate Cox regression analysis showed that there was no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus for all-cause death (PD/HD, HR=1.171, 95% CI 0.426-3.223, P=0.760). Multivariate Cox regression analysis showed that there was no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus (PD/HD, HR=1.460, 95% CI 0.515-4.144, P=0.477), and high plasma albumin ( HR=0.893, 95% CI 0.813-0.981, P=0.019) was an independent protective factor for survival in ESRD patients without diabetes mellitus. There was still no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus after using IPTW (PD/HD, HR=1.842, 95% CI 0.514-6.604, P=0.348). Conclusion:The difference of cumulative survival rates between HD and PD is not significant in ESRD patients without diabetes mellitus.
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Objective:To investigate the expression level of vitamin D receptor (VDR) in podocytes of diabetic kidney disease (DKD) and its role in podocyte injury and proteinuria.Methods:(1) Sixty-five patients who had been diagnosed with type 2 diabetes mellitus (with or without albuminuria) were enrolled in this study and 25 age-and sex-matched healthy control subjects were enrolled. According to the ratio of urinary excretion of albumin/creatinine (ACR), the type 2 diabetes mellitus patients were classified into without proteinuria group (ACR<30 mg/g, n=24), microalbuminuria group (ACR 30-300 mg/g, n=18) and clinical proteinuria group (ACR>300 mg/g, n=23). Another 25 patients with DKD confirmed by renal biopsy were selected as the DKD group. Normal kidney tissue samples were taken from the same period of urinary surgical department for 10 cases of renal tumors in patients with renal resection. The test indicators in each group were compared. The VDR expression in blood, urine samples and kidney tissues of patients was detected by real-time quantitative PCR, ELISA and immunohistochemistry, and then were compared among different groups. The correlation between VDR and ACR was analyzed by Pearson correlation analysis. (2) Male db/db mice with genetic background of C57BLKs/J and db/m mice born in littermates were randomly divided into normal control group (group A), DKD control group (group B), DKD treated with dimethyl sulfoxide group (group C), DKD treated with paricalcitol (VDR agonist) group (group D). The C and D groups were treated by continuous intraperitoneal injection for 8 weeks, and the group A and B were not treated. The mice were started to intervene continuously for 8 weeks at the age of 10 weeks. At 22 weeks of age (12 weeks after starting intervention), the biochemical indexes of the mice's body weight, blood and urine were compared. The changes of β-catenin and VDR were detected by Western blotting. The expressions of podocyte marker protein podocin and podocyte injury protein α-SMA were observed by immunofluorescence. Results:(1) Compared with the normal healthy control group, the plasma levels of VDR mRNA and protein in diabetic patients without proteinuria, microalbuminuria and clinical proteinuria were lower (all P<0.05). Compared with the diabetic patients without proteinuria, the plasma levels of VDR mRNA and protein in diabetic patients with microalbuminuria and clinical proteinuria were lower (all P<0.05). (2) Compared with the normal healthy control group, the plasma levels of VDR mRNA and protein in diabetic patients without proteinuria and DKD patients were lower (all P<0.05). Compared with diabetic patients without proteinuria, the plasma levels of VDR mRNA and protein in the DKD group were also lower (both P<0.05). (3) Immunohistochemical results showed that the expression of VDR in kidney tissue of DKD group was significantly lower than that of normal control group. (4) The relative level of VDR mRNA in plasma of patients with DKD was negatively correlated with ACR ( r=-0.342, P<0.05). (5) The levels of VDR in urine supernatant of each group showed opposite trends with the plasma levels. (6) Western blotting results showed that the expression of β-catenin protein in groups B and C was higher than that in group D (both P<0.05), and the expression of VDR protein was lower than that in group D (both P<0.05). Immunofluorescence results showed that the expression of podocin in groups B and C was lower than that in group D (both P<0.05), and the expression of α-SMA was higher than that in group D (both P<0.05). Conclusion:VDR overexpression relieves podocyte injury and proteinuria in DKD.
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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.
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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.
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Objective To sum up and analyze the clinical and pathological characteristics in patients with both IgA nephropathy (IgAN) and diabetes mellitus. Methods A total of 500 patients were recruited, including 25 patients with both IgAN and diabetes mellitus, and 475 patients with IgAN only, who were diagnosed by renal-biopsy during Jan 2015 to Jan 2017 at the First Affiliated Hospital of Zhengzhou University. The clinical and pathological data were collected and analyzed using SPSS 22.0. Propensity Score Matching was used to match and select the patients in the both groups, and thereafter the depth of the basement membrane from the matched patients were compared using electron microscopy. The data of the patients whose follow - up time was ≥3 months were retrospectively collected, and Kaplan-Meier analysis was used to compare the difference of the prognosis. Results Compared to the patients with IgAN only, patients with both IgAN and diabetes mellitus were older [(46.36±13.49) years vs (34.00±13.80) years, P<0.001], had higher level of serum triglyceride [2.06(1.52, 3.11) mmol/L vs 1.51(1.01, 2.25) mmol/L, P=0.012] and thicker basement membrane [(384.33 ± 61.20) nm vs (346.72 ± 52.65) nm, P=0.044]. The patients with both IgAN and diabetes mellitus were more prone to reach the composite endpoint [4/7(57.14％) vs 25/265(9.33％), P<0.001] and had worse prognosis (Log-Rank test, P=0.004). Conclusions IgAN patients with diabetes mellitus have different clinical, pathological characteristics and prognosis from patients with IgAN alone. These patients need to be closely monitored and actively treated.
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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.
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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.
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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.
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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.
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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.
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Objective To reduce the incidence of peritoneal dialysis related peritonitis for patients in rural area and to improve management quality of peritoneal dialysis center.Methods We established multidisciplinary collaborative research group involving departments of nephrology,nutrition,infection,and quality control.Risk factors of peritoneal dialysis related peritonitis in rural patients were analyzed,and prevention measures were designed.The rate of peritoneal dialysis related peritonitis in 89 patients after implementation was analyzed.Results The rate of peritoneal dialysis related peritonitis was decreased from 43 patient·month per time to 67 patient ·month per time.Conclusion The compound pathway can effectively reduce the rate of peritonitis,improve patient satisfaction,and prolong dialysis age.
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Objective To observe the role and related mechanism of chemerin and its receptor ChemR23 in glomerular endothelial cells (GEnCs) stimulated by high glucose.Methods Mouse GEnCs were cultured and divided into control group,20.0 mmol/L high glucose group,40.0 mmol/L high glucose group and mannitol control group.Then the expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell culture supematant as well as the expressions of intracellular protein and mRNA of chemerin,ChemR23,IL-6 and TNF-α were detected.Lentiviral transfection targeting ChemR23 was applied before high glucose-or Chemerin-stimulated,and expressions of supernatant and intracellular mRNA of IL-6 and TNF-α were measured.Meanwhile whether p38 mitogen-activated protein kinase (p38 MAPK) pathway was activated by high glucose was detected.The specific inhibitor of p38 MAPK was added prior to high glucose-stimulated,then supernatant and intracellular mRNA expressions of IL-6 and TNF-α was detected.The supernatant expressions of IL-6 and TNF-α were measured by ELISA.The intracellular protein expression and p38 MAPK phosphorylation activity were detected by Western blotting.The mRNA expression was detected by real time PCR.Results Compared with those in the control group,in high glucose groups the expressions of IL-6,TNF-α and chemerin were significantly increased (all P ＜ 0.05),however,the expressions of ChemR23 did not change (all P ＞ 0.05);the supernatant and mRNA expressions of IL-6 and TNF-α were also elevated in the chemerin group (all P ＜ 0.05).Lentivirus baring shRNA could efficiently suppress ChemR23 expression,and the Chemerin-or high glucose-induced expressions of IL-6 and TNF-α were reduced (all P ＜ 0.05).Also it could significantly reduce the expression of phosphorylated-p38 MAPK (p-p38 MAPK) induced by high glucose (P ＜ 0.05),as high glucose group had higher p-p38 MAPK than control group (P ＜ 0.05).While the high glucose-elevated expressions of IL-6 and TNF-α were significantly attenuated by p38 MAPK inhibitor (all P ＜ 0.05).Conclusions High glucose stimulation can induce the expression of chemerin in GEnCs.By binding to ChemR23,chemerin activates p38 MAPK signaling pathway,and then promotes the expressions of IL-6 and TNF-α.These inflammatory cytokines aggravate inflammation of GEnCs.
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Objective To investigate the efficacy and feasibility of combination of leflunomide and clopi-dogrel in the treatment of IgA nephropathy. Methods 84 patients with primary IgA nephropathy were randomly divided into four groups: Control group (group 1) received valsartan; test group (group 2) received valsartan +clopidogrel; group 3 received valsartan + leflunomide; group 4 received valsartan + clopidogrel + leflunomide. The level of 24 h urinary protein,serum creatinine, glomerular filtration rate and therapeutic efficacy, adverse reactions were detected and recorded during the 48 weeks follow-up. Results The 24 h urinary protein of 84 patients showed a downward trend during the course of treatment , but there were statistical differences between groups since 8 weeks after treatment (P < 0.05). The level of urine protein in group 3 and group 4 decreased significantly to 61.48% and 67.23% respectively in 48 weeks after treatment. At the end of the follow up , the serum creatinine levels in group 1 and group 2 significantly increased while the glomerular filtration rate de-creased obviously (P < 0.05). Conclusion The combination of leflunomide with clopidogrel could reduce the level of urinary proteins and slow renal function deterioration in the treatment of IgA nephropathy with less ad-verse reactions. This study provides a new idea for treatment of IgA nephropathy.
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Objective To investigate the effects of cyclooxygenase-2 (COX-2) inhibitor on peritoneal lymphangiogenesis and peritoneum function in uremic rat.Methods Uremic rats treated by peritoneal dialysis were intragastric administration celecoxib.Structures of peritoneum,peritoneal function,peritoneal lymphatic vessel density (LVD) were detected in every group.The mRNA of vascular endothelial growth factor-C (VEGF-C),lymphatic vessel endothelial hyluronan receptor-1 (LYVE-1) and COX-2 were tested by RT-PCR.The protein expressions of LYVE-1,VEGF-C,COX-2 were tested by western blot.Results With the extension of the duration of dialysis,the peritoneum thickness was increasing,inflammatory cell infiltrated obviously,uhrafiltration volume decreased significantly.But the celecoxib could increase uhrafiltration volume and reduce the glucose transport rate(P ＜0.05).Compared with the normal group,the levels of LVD,COX-2,VEGF-C,and LYVE-1 mRNA and protein were significantly up-regulated in uremic and dialysis groups (P ＜0.05).Compared with the uremic dialysis group,the levels of LVD,COX-2,VEGFC and LYVE-1 mRNA and protein were significantly down-regulated in the celecoxib group.There was a positive correlation between COX-2 and VEGF-C,LVD in protein levels,as well as VEGF-C and LVD (all P values ＜ 0.05).Conclusions Hyper glucose dialysis solution and uremic condition could up-regulate the expression of COX-2,VEGF-C,LYVE-1 in gene and protein level and stimulate lymphangiogenesis.COX-2 inhibitor could delay the change of peritoneal structures and function.COX-2 inhibitor could prevem the lymphangiogenesis in uremic rat treated by peritoneal dialysis,which might down-regulate the expression of VEGF-C by COX-2 depended manner.
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Objective To investigate the effects of the cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on angiogenesis and peritoneal function of uremic peritoneal dialysis rats.Methods Forty-eight male SD rats were selected,and they were randomly divided into five groups:normal control group(n =8),sham operation group(n =8),uremia group(5/6 nephrectomy,n =8),PD group [4.25％ PD solution,2 weeks PD model(n =8) and 4 weeks PD model(n =8)],PD + celecoxib intervention group[treated by celecoxib(20 mg/kg) via oral gavage,n =8].The peritoneum of uremic peritoneal dialysis rats was observed in different dialysis time from peritoneal structures,functions,peritoneal tissue capillary density (microvessel density,MVD) and COX-2,vascular endothelial growth factor (VEGF) expression level,and the impacts of celecoxib on uremic peritoneal dialysis rats peritoneal angiogenesis and peritoneal function were study.Results With the conduct of the peritoneal dialysis,peritoneal thickness increased,the inflammatory cells infiltrated,peritoneal equilibration test (PET) showed that ultrafiltration volume decreased significantly (P ＜ 0.05),the amount of glucose transport rate rised significantly (P ＜ 0.05),but the celecoxib could improve net ultrafiltration volume (P ＜ 0.05),and reduce the glucose transport rate (P ＜ 0.05).The peritoneal tissue MVD and COX-2,VEGF expression were significantly increased in uremia group and PD group compared with that in the normal control group (all P ＜ 0.05),were significantly lower in PD + Celecoxib intervention group than that in uremia group (P ＜ 0.05).The correlation analysis showed that the level of COX-2 protein expression with MVD,VEGF protein expression was positively correlated (both P ＜ 0.05),the level of VEGF protein expression and MVD was positively correlated (P ＜ 0.05).Conclusions In vivo high glucose dialysate and uremia environmental can stimulate the COX-2 and VEGF expression raised,and the capillaries production increased in peritoneal tissue.Celecoxib can alleviate the change of peritoneal tissue morphology and function in long-term peritoneal dialysis rats.Celecoxib inhibits the peritoneal neovascularization of uremic peritoneal dialysis rats,possibly through inhibition of COX-2 expression to reduce the production of VEGF.
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Objective To investigate the effect of soluble Tie2 fusion protein(sTie2/Fc)on the angiogenesis of peritoneal vessels in uremic peritoneal dialysis (PD) rats.Methods Rats were randomly divided into 6 groups:normal rats as control group (group1),rats with sham operation (group2),uremic rats without PD (group3),uremic rats dialyzed with 4:25％ PD solution (group4),uremic rats dialyzed with 4.25％ PD solution and treated by subcutaneous injection of 2.5 μg/kg sTie2/Fc (group5),uremic rats dialyzed with 4.25％ PD solution and treated by subcutaneous injection of 5.0 μg/kg sTie2/Fc (group6).sTie2/Fc was given every other day during peritoneal dialysis period,total 14 doses.After regular PD for 28 days,RT-PCR and tissue immunohistochemical staining were used to detect the mRNA and protein expressions of Angpt-2 in peritoneal tissues in each group of rats.Microvessel density (MVD) of peritoneum was detected and quantified with immunohistochemical staining by using anti-CD34 antibody.Results The expression of Angpt-2 mRNA and protein was found in each group.There was no significant difference of.Angpt-2 expression both in mRNA and protein level between group1 and group2.Compared with group1,the mRNA and protein expression of Angpt-2 were significantly increased in group3 and group4 (all P＜0.05).Compared with group3,the mRNA and protein expression of Angpt-2 were significantly increased in group4 (all P＜0.05).Compared with group 4,the mRNA and protein expression of Angpt-2 were significantly decreased in group5 and group6 (all P＜0.05).Compared with group5,the mRNA and protein expression of Angpt-2 were significantly decreased in group6 (all P＜0.05).Only few new microvessel was found in group1 and group2.Compared with group1,MVD was significantly up-regulated in group3 and group4 (all P＜0.05).Compared with group4,MVD was significantly down-regulated in group5 and group6 (all P＜0.05).Conclusions Peritoneum neoangiogensis can be effectively inhibited by sTie2/Fc in uremic rat treated with PD.Blocking of signal transduction may be involved in the mechanism of sTie2/Fc inhibiting peritoneal angiogenesis.