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Objective:To investigate the effect of pirfenidone (PFD) on the proliferation of human glomerular mesangial cells (HMC) stimulated by serum IgA1 in patients with IgA nephropathy (IgAN) and its possible mechanism.Methods:Serum IgA1 of IgAN patients was purified by Jacalin affinity chromatography combined with Sephacryl S-200 gel filtration, and then heated to aggregated form (aIgA1). CCK8 method was used to confirm the concentration and time of PFD. The cells were divided into blank control group, IgA1 (0.5 mg/ml) group and IgA1 (0.5 mg/ml)+PFD (2 mmol/L) group. The CCK8 method was used to detect proliferation of mesangial cells. The cell cycle was detected by flow cytometry, and the proliferation index of mesangial cells was calculated. The expression levels of transforming growth factor β1 (TGF-β1), Smad4, Smad7, fibronectin (FN) and collagen Ⅳ protein and mRNA were detected through Western blotting and real-time PCR.Results:Compared with blank control group, the proliferation of HMC was promoted significantly by aIgA1 ( P<0.05). After PFD treatment, the proliferation of HMC was significantly inhibited ( P<0.01). Compared with the blank control group, the number of G1 phase cells decreased, the number of S phase cells and cell proliferation index increased in IgA1 group (all P<0.05). Compared with IgA1 group, the number of cells in G1 phase increased significantly, the number of cells in S phase and G2/M phase decreased significantly, and the cell proliferation index decreased in IgA1+PFD group (all P<0.05). Western blotting and real-time PCR results showed that compared with the blank control group, the protein and mRNA expressions of collagen Ⅳ, FN and Smad4 in HMC stimulated by aIgA1 were significantly increased, while TGF-β1 protein expression was increased and Smad7 protein expression was decreased (all P<0.05). After PFD treatment, the protein and mRNA expression of collagen Ⅳ, FN and Smad4 in HMC was significantly decreased, while TGF-β1 protein expression was obviously decreased, and Smad7 protein was up-regulated (all P<0.05). There was no significant difference in the mRNA expression of TGF-β1 and Smad7 in each group before and after PFD treatment (all P>0.05). Conclusions:PFD can increase the arrest of HMC in G1 phase, inhibit the proliferation of HMC induced by aIgA1 of IgAN patients, and reduce the production of extracellular matrix. The mechanism may be related to up-regulation of Smad7 expression and down-regulation of TGF-β1/Smad4 pathway.
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Objective To explore the reasons for withdrawal from peritoneal dialysis (PD) in our hospital.Methods This was a single-center,retrospective cohort study.Patients who started PD in the Department of Nephrology,the First Affiliated Hospital of Nanchang University from November 1st,2005 to February 28th,2017,were enrolled,and followed up to May 31,2017.Patients who continued PD after May 31,2017 were as the control group.Patients who withdrew from PD were divided into 4 subgroups:death group,hemodialysis group,kidney transplantation group and loss of follow-up group.The clinical characters of 4 subgroups were compared with the control group.Results A total of 998 patients were enrolled with age of (49.36± 14.94) when PD started and median dialysis duration of 27.13(12.84,42.29) months,in whom 570 patients (57.11％) were male.Five hundred and seventeen dropout events were recorded,and the dropout rate was 51.80％.The main reason for withdrawal from PD was death (258 patients,49.90％),followed by hemodialysis (166patients,32.11％),kidney transplantation (66 patients,12.77％) and loss to follow-up (27 patients,5.22％).The leading cause of death was cardio-cerebro-vascular diseases (136 cases,52.71％),followed by infection (42 cases,16.28％),dyscrasia (20 cases,7.75％) and tumor (5 cases,1.94％).The main reason for transfering to hemodialysis was insufficient dialysis (76 cases,45.78％),followed by peritonitis (55 cases,33.13％) and catheter dysfunction (24 cases,14.46％).Compared with those in the control group,in the death group patients were older at PD commencement,and had higher proportions of hypertension,diabetes and cardio-cerebro-vascular diseases (all P ＜ 0.05).The proportions of male and diabetes mellitus were higher in the hemodialysis group than those in the control group (both P ＜0.05).Biochemical indicators showed that serum albumin and blood phosphorus were lower in the death group than those in the control group (both P ＜ 0.05);blood albumin was significantly lower in the hemodialysis group than that in the control group (P ＜ 0.05).Conclusions The main reasons for withdrawal from PD in our center are death and transfering to hemodialysis.The cardio-cerebro-vascular disease is the leading cause of death,and inadequate dialysis is the main reason for transfering to hemodialysis.
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Objective To explore the risk factors and characteristics in patients with peritoneal dialysis who died in different periods.Methods The clinical data of new peritoneal dialysis patients in the Department of Nephrology and Peritoneal Dialysis Center of the First Affiliated Hospital of Nanchang University from November 1,2005 to February 28,2017 was retrospectively analyzed.The patients were divided into two groups according to the time of death:those who died within one year and died after one year.The risk factors of mortality between the two groups were analyzed by Cox regression model.Results A total of 997 patients were enrolled and 244 patients died.There were 69 patients (28.3％) died within one year and 175 patients (71.7％) died after one year.Cardiovascular and cerebrovascular disease was the dominating reason of death in both groups,accounting for 59.4％ (died within one year group) and 51.4％ (died after one year group) respectively.Cox regression analysis showed that for died within one year group,old age (HR=1.035,95％ CI:1.016-1.055,P＜ 0.001),low blood total calcium (HR=0.167,95％ CI:0.053-0.529,P=0.002),low albumin (HR=0.899,95％CI:0.856-0.943,P ＜ 0.001) and low apolipoprotein A1 (HR=0.274,95％CI:0.095-0.789,P=0.016) were risk factors associated with mortality.However,for died after one year group,old age (HR=1.053,95％CI:1.038-1.069,P ＜ 0.001),combined with diabetes (HR=2.181,95％CI:1.445-3.291,P ＜ 0.001) and hypertriglyceride (HR=l.204,95％CI:1.065-1.362,P=0.003) were risk factors associated with mortality.Conclusions The risk factors of mortality for peritoneal dialysis patients of different periods were not exactly the same.For died within one year patients,old age,low blood total calcium,low albumin and low apolipoprotein A1 were independent risk factors for mortality.However,for died after one year patients,old age,combined with diabetes,and high triglycerides were independent risk factors for mortality.
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Objective To investigate the risk factors of all-cause mortality in diabetic patients on peritoneal dialysis (PD).Methods As a single-center retrospective cohort study,all incident PD patients who were catheterized at the First Affiliated Hospital of Nanchang University between November 1,2005 and February 28,2017 were included.Patients were divided into diabetes mellitus group (DM group) and non-diabetes mellitus group (NDM group).Outcomes were analyzed by Kaplan-Meier method.Multivariate Cox proportional hazards models were utilized to assess the risk factors of all-cause mortality.Results A total of 977 patients were enrolled.Compared with NDM group,patients in DM group were older (47.5±14.4 vs 59.3±11.3,P ＜ 0.01),had more cardiovascular disease (CVD) (7.5％ vs 20.3％,P ＜ 0.01),higher levels of serum hemoglobin (78.2±17.2 vs 82.3±14.6g/L,P ＜ 0.01),and lower levels of serum albumin (36.1±5.0 vs 32.7±5.6 g/L,P ＜ 0.01).The one-,three-and five-year patient survival rates of DM and NDM group were 89.7％,56.0％,31.9％ and 94.7％,81.3％,67.4％,respectively.Survival rate was significantly lower in DM group than in NDM group (x2=63.51,P ＜ 0.01).Stratified analysis showed that DM group had significant lower survival rate than NDM group in patients younger than 70 years old (x2=73.35,P ＜ 0.01),while survival rate was similar between the two groups patients older than 70 years old (x2=0.003,P=0.96).Multivariate Cox proportional hazards model analysis showed that DM (HR:1.74,95％CI:1.27-2.38,P ＜ 0.01),age (HR:1.05,95％CI:1.04-1.06,P ＜ 0.01),leukocyte (HR:1.06,95％CI:1.00-1.12,P=0.04) and triglyceride (HR:1.19,95％CI:1.07-1.32,P ＜ 0.01) were all independent risk factors for all-cause mortality of PD patients.However,age (HR:1.05,95％CI:1.04-1.07,P＜ 0.01) and alkaline phosphatase (HR:1.01,95％ CI:1.00-1.01,P=0.02) were independent risk factors for all-cause mortality of diabetic patients.Conclusions Long-term survival rate was lower in diabetic PD patients than in non-diabetic PD patients.DM,age,leukocyte and triglyceride were independent risk factors of mortality in PD patients.Age and alkaline phosphatase were independent risk factors of mortality in diabetic patients.