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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 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 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 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 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 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 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 observe the expression of heparanase(HPA)in kidney of diabetic nephropathy(DN)rats and to investigate the role of HPA in the pathogenesis of proteinuria in DN rals. Methods DM rat models induced by intraperitoneal injection with streptozotocin were constnmted.Twenty-six rats were randomly divided into heahhy control group(n=6),DM6-week group(n=10)and DM 12-week group(n=10).Relative kidney weight(RKW),blood glucose,BUN,Scr,24-hour urine volume and(t 24-hour proteinuria quantilation were measured,and renal morphology was observed after 6 and 12 weeks.The expression of HPA was examined by immunohistochemistry and reverse transcription PCR. Results (1)Conq)ared with the control group,RKW,blood glucose,BUN,24-hour urine volume and 24-hour proteinuria quantitation of DM groups increased markedly(P＜0.05 orP＜0.01).(2)Compared to the control group,the expression of HPA mRNA and protein in DM groups increused significantly(P＜0.01).(3)HPA protein and mRNA were positively correlated with the quantification of urinary prolein (r=0.783,P＜0.01;r=0.793,P＜0.01). Conclusion The increased expression of HPA maybe parlicipate in the pathogenesis of proteinuria in DN.