Comparative Study of Renal Replacement Therapy in Korean Diabetic End-Stage Renal Disease Patients: a Single Center Study

The number of diabetic ESRD patients has increased and death rates of diabetic patients on hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation (RT) have remained higher than the death rate of non-diabetic patients. An attempt was made to compare the clinical characteristics, patients' cumulative survival, and technical survival among the three groups retrospectively according to the mode of renal replacement therapy (RRT), and to analyze the risk factors associated with mortality. A total of 229 diabetic ESRD patients diagnosed between 1986 and 1995 at the Severance Hospital who began dialysis or who underwent a kidney transplant were included and their medical charts were reviewed. Hypertension was the most common co-morbid disease in all study groups. The prevalence of cardiovascular disease was the only co-morbid condition that was significantly different among the three groups, which was highest in the PD group (24.4%) and lowest in the RT group (8%). In the analysis of a patient's cumulative survival rate not adjusted for age and sex, the RT group had the highest survival rate, and the cumulative survival rate of the HD and PD group were similar. The 5-year survival rate of the patients treated with HD, PD and RT was 28.8%, 19.8%, and 72.0%, respectively. No differences were observed in the patient's cumulative survival rate between the HD and PD patients even when it was adjusted for age. When adjusted for age, sex and risk factors, the relative death rate of the RT group was significantly lower in male patients younger than 60 years of age. With the exception of male patients younger than 60 years of age, the PD group showed a slightly lower relative death rate although it was not significant. The multiple Cox regression analysis of patient survival showed that age, serum albumin, BUN, mean hospital days, the presence of cardiovascular disease at the initiation of RRT were associated with mortality. The analysis of the technique survival rate revealed a better result in the HD group compared to PD group, but a limitation in being able to investigate the AVF function disturbed the accuracy of the analysis of technical survival rate. In conclusion, the survival rate between the PD and HD patients was not different and the RT group had the best survival rate. Therefore, kidney transplantation in diabetic ESRD patients should be considered positively if no other contraindicated condition for RT exit.

Changes of ZO-1 Expression in Diabetic Rat Glomeruli and Cultured Mouse Podocyte Under High Glucose Conditions and the Effect of Angiotensin II Type 1 Receptor Blocker / 대한신장학회잡지

BACKGROUND: Diabetic nephropathy (DN) is clinically characterized by persistent proteinuria. The underlying pathologic changes responsible for the nephropathy are the loss of size selective and/or charge selective properties of the glomerular filtration barrier. Size selectivity is maintained primarily by the slit diaphragm and ZO-1 is one of the basic components of it. However, the precise role of the ZO-1 in the pathogenesis of the glomerular diseases is not fully understood. We investigated the changes of ZO-1 expression in diabetic glomeruli in vivo, and by high glucose in cultured podocyte in vitro. We also evaluated the effect of angiotensin II type 1 receptor blocker (ARB) on the ZO-1 changes induced by diabetes or high glucose. METHODS: To determine the effect of ARB on podocytes ZO-1 protein and mRNA expression, immortalized mouse podocytes were incubated with RPMI medium containing normal glucose (NG, 5.6 mM) or high glucose (HG, 30 mM) with or without ARB (10-6 M, L-158, 809). For animal studies, rats were injected with diluent (Control, C, n=18) or streptozotocin. The latter were left untreated (DM, n=18) or treated with 1 mg/kg/day ARB (DM+ARB, n=18). Six rats from each group were sacrificed monthly, and Western blot and RT?PCR were performed for ZO-1 with sieved glomeruli. Renal sections were stained for ZO-1 by immunohistochemistry. RESULTS: The ZO-1 mRNA and protein expressions in podocytes exposed to HG conditions were significantly higher than those in podocytes exposed to NG media (p<0.05). ARB treatment inhibited the HG induced increase in ZO-1 mRNA and protein expression by 73% and 64%, respectively (p<0.05). Compared to the C rats (19.8+/-3.2 mg/day), 24 hour urinary protein excretion at 3 month was significantly higher in the DM rats (90.6+/-11.3 mg/day, p< 0.05), and ARB treatment partly reversed the increase in proteinuria in DM rats (51.6+/-6.6 mg/day, p<0.05). Glomerular ZO-1 mRNA and protein expressions were also significantly increased in DM than corresponding C at all duration (p<0.05). ARB treatment for 3 months in DM rats inhibited the increase in ZO-1 mRNA and protein expression by 57.5% and 70.6%, respectively (p<0.05). ARB treatment for 3 months significantly ameliorated increased glomerular ZO-1 expression in DM rats as assessed by immunohistochemistry. CONCLUSION: In conclusion, ZO-1 mRNA and protein expressions were increased in podocytes exposed to HG and in DM glomeruli, and this increment in ZO-1 expression was ameliorated with ARB. Taken together, these data suggest that change of ZO-1 expression in podocytes is implicated in the early changes of diabetic nephropathy and may contribute to the development of proteinuria.