Jang-Hee Cho

Survival advantage of peritoneal dialysis relative to hemodialysis in the early period of incident dialysis patients: a nationwide prospective propensity-matched study in Korea.

Background The impact of dialysis modality on survival is still somewhat controversial. Given possible differences in patients’ characteristics and the cause and rate of death in different countries, the issue needs to be evaluated in Korean cohorts. Methods A nationwide prospective observational cohort study (NCT00931970) was performed to compare survival between peritoneal dialysis (PD) and hemodialysis (HD). A total of 1,060 end-stage renal disease patients in Korea who began dialysis between September 1, 2008 and June 30, 2011 were followed through December 31, 2011. Results The patients (PD, 30.6%; HD, 69.4%) were followed up for 16.3±7.9 months. PD patients were significantly younger, less likely to be diabetic, with lower body mass index, and larger urinary volume than HD patients. Infection was the most common cause of death. Multivariate Cox regression with the entire cohort revealed that PD tended to be associated with a lower risk of death compared to HD [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.36–1.08]. In propensity score matched pairs (n = 278 in each modality), cumulative survival probabilities for PD and HD patients were 96.9% and 94.1% at 12 months (P = 0.152) and 94.3% and 87.6% at 24 months (P = 0.022), respectively. Patients on PD had a 51% lower risk of death compared to those on HD (HR 0.49, 95% CI 0.25–0.97). Conclusions PD exhibits superior survival to HD in the early period of dialysis, even after adjusting for differences in the patients’ characteristics between the two modalities. Notably, the most common cause of death was infection in this Korean cohort.

Effect of Biocompatible Peritoneal Dialysis Solution on Residual Renal Function: A Systematic Review of Randomized Controlled Trials

♦ Introduction: Residual renal function (RRF) plays an important role in outcome of peritoneal dialysis (PD) including mortality. It is, therefore, important to provide a strategy for the preservation of RRF. The objective of this study was to evaluate relative protective effects of new glucose-based multicompartmental PD solution (PDS), which is well known to be more biocompatible than glucose-based conventional PDS, on RRF compared to conventional PDS by performing a systematic review (SR) of randomized controlled trials. ♦ Methods: We searched studies presented up to January 2014 in MEDLINE, EMBASE, the COCHRANE library, and local databases. Three independent reviewers reviewed and extracted prespecified data from each study. The random effects model, a more conservative analysis model, was used to combine trials and to perform stratified analyses based on the duration of follow-up. Study quality was assessed using the Cochrane Handbook for risk of bias. Eleven articles with 1,034 patients were identified for the SR. ♦ Results: The heterogeneity of the studies under 12 months was very high, and the heterogeneity decreased substantially when we stratified studies by the duration of follow-up. The mean difference of the studies after 12 months was 0.46 mL/min/1.73 m2 (95% confidence interval = 0.25 to + 0.67). ♦ Conclusion: New PDS showed the effect to preserve and improve RRF for long-term use compared to conventional PDS, even though it did not show a significant difference to preserve RRF for short-term use.

Successful withdrawal of antiviral treatment in kidney transplant recipients with chronic hepatitis B viral infection.

The optimal duration of antiviral therapy for kidney transplant recipients (KTR) with chronic hepatitis B virus (HBV) infection remains unclear. We reported the long‐term outcomes after withdrawal of antiviral agent in KTR with chronic HBV infection.

Successful treatment of recurrent focal segmental glomerulosclerosis with a low dose rituximab in a kidney transplant recipient

Abstract Recurrence of focal segmental glomerulosclerosis (FSGS) is a major therapeutic challenge in kidney transplantation (KT). Although intensive plasmapheresis and high-dose rituximab have been introduced to treat recurrent FSGS, the most effective dosage and regimen of rituximab have not been determined. Herein we reported the first case of successful treatment of recurrent FSGS with a low-dose rituximab. The patient showed marked proteinuria (3.5 g/d) and oliguria 2 d after KT. Two courses of plasmapheresis and immunoglobulin were applied to the patient, however, nephrotic range proteinuria persisted and creatinine level increased to 3.56 mg/dL. Five months post-transplant, the patient received injection with only one dose of rituximab 100 mg, without further plasmapheresis, which resulted in immediate reduction of serum creatinine and full remission of proteinuria during the following 18 months. This case suggested that recurrent FSGS, which frequently relapses after plasmapheresis, could be treated successfully with a low-dose rituximab even without plasmapheresis.

CYP3A and ABCB1 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of tacrolimus and its metabolites (M-I and M-III).

Background We prospectively studied renal transplant recipients receiving tacrolimus to determine the relationship between the CYP3A4, CYP3A5, and ABCB1 genetic polymorphisms and the pharmacokinetics (PK) and pharmacodynamics (PD) of tacrolimus and its metabolites. Methods Renal transplant recipients receiving tacrolimus were genotyped for CYP3A4*4, CYP3A4*5, CYP3A4*18, CYP3A5*3, ABCB1 c.1236C→T, ABCB1 c.2677G→A/T, and ABCB1 c.3435C→T. Dose-adjusted trough concentration (C0) of tacrolimus and its metabolites (M-I and M-III) and PK and PD (T-cell and monocyte subsets) were determined on transplantation days –2, 5, 30, and 90 and correlated with the corresponding genotypes. Results The dose-adjusted C0 of tacrolimus and its metabolites and AUC0–12 were significantly higher and the mean fluorescence intensity (MFI) of HLA/DR+ in monocytes was significantly lower in patients with CYP3A5*3/*3 than in patients with CYP3A5*1/*1 or CYP3A5*1/*3. However, there was no significant difference in the dose-adjusted C0 of tacrolimus and its metabolites, PK and PD among the ABCB1 genotypes. The MFI of HLA/DR+ in monocytes showed a significant negative correlation with dose-adjusted C0 of tacrolimus and its metabolites and AUC0–12. In a multiple regression analysis, the presence of the CYP3A5*3/*3 genotype was a significant independent variable determining the dose-adjusted C0 of tacrolimus and its metabolites, AUC0–12, and the MFI of HLA/DR+ in monocytes. Conclusions This study demonstrates that the CYP3A5 genetic polymorphisms are associated with the individual differences in PK and PD as well as in C0 of tacrolimus and its metabolites. The MFI of HLA/DR+ in monocytes might be considered to be a significant tool for monitoring tacrolimus efficacy.

Differential Effect of Viral Hepatitis Infection on Mortality among Korean Maintenance Dialysis Patients: A Prospective Multicenter Cohort Study

The role of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of survival among dialysis patients remains incompletely understood. In the present multicenter prospective cohort study, we investigated the prevalences of HBV and HCV infection among 3,321 patients receiving maintenance dialysis in Korea, and assessed the impacts of these infections on survival. All included patients underwent hepatitis B antigen (HBsAg) and HCV antibody (Ab) testing, which revealed that 236 patients (7.1%) were HBsAg-positive, and 123 patients (3.7%) were HCV Ab-positive. HBsAg-positive and HCV Ab-positive patients were matched to hepatitis virus-negative patients using a propensity score at a ratio of 1:2. The prevalences of HBV and HCV infection did not significantly differ according to dialysis modality. Linear-by-linear association analysis revealed that hepatitis B prevalence significantly increased with increasing dialysis vintage (p = 0.001), and hepatitis C prevalence tended to be higher with increasing dialysis vintage (p = 0.074). We compared the survival of HBsAg-positive and HCV Ab-positive patients to that of hepatitis virus-negative patients. After propensity score matching, cumulative survival did not differ between HBsAg-positive and HBsAg-negative patients (p = 0.37), while HCV Ab-positive patients showed significantly lower survival than HCV Ab-negative patients (p = 0.03). The main conclusions of the present study are that HBV infection prevalence increased with longer dialysis vintage, and that both HBV and HCV infections were most prevalent among patients with the longest dialysis vintage. Additionally, HCV infection among maintenance dialysis patients is associated with an increased risk of mortality.

Assessment of fluid and nutritional status using multifrequency bioelectrical impedance analysis in peritoneal dialysis patients.

Background/Aims: The purpose of this study was to evaluate the clinical usefulness and relevance of bioelectrical impedance analysis (BIA) for assessing the fluid and nutritional status in peritoneal dialysis (PD) patients. Methods: Statistical analyses between various measures of fluid and nutritional status were performed in 106 cases of 64 patients. Results: Extracellular fluid/total body water (ECF/TBW) was correlated with systolic blood pressure, extremity edema, and antihypertensive medications (p = 0.042, p < 0.001, and p = 0.029, respectively). Body cell mass (BCM)/height2 was correlated with SGA rating and PCR (p < 0.001 and p = 0.002, respectively). ECF/TBW and BCM/height2 significantly predicted extremity edema (p < 0.001) and SGA rating (p = 0.001), respectively. ROC analysis yielded an ECF/TBW cut-off of 0.36 and a BCM/height2 cut-off of 11.23. When the BCM/height2 cut-off of 11.23 was applied to subclinical patients (SGA score ≥6), a significant difference in SGA rating was detected in subgroups (p = 0.010). Conclusion: BIA yields useful and relevant information about hydration and nutritional status in PD patients.

Aquaporin 3 expression is up-regulated by TGF-β1 in rat peritoneal mesothelial cells and plays a role in wound healing.

Aquaporin 3 (AQP3) is expressed in many tissues including the peritoneum and kidney. In cultured mesothelial cells, glucose up-regulates AQP3, which may be important for water transport through the peritoneal membrane. However, there has been no research into the role of AQP3 in human peritoneal mesothelial cell (HPMC) migration or peritoneal fibrosis. We investigated the effects of transforming growth factor-β1 (TGF-β1) on AQP3 expression in HPMCs. We also investigated the role of AQP3 in the peritoneal wound healing process in rats. Chronic exposure to glucose-containing solution increased peritoneal myofibroblasts, with TGF-β1 and AQP3 expression in a model of long-term peritoneal dialysis. In vitro, TGF-β1 induced AQP3 expression in HPMCs. AQP3 knockdown by small-interfering RNA inhibited TGF-β1-induced AQP3 and α-smooth muscle actin expression and also slowed HPMC migration. AQP3 overexpression induced faster migration of HPMCs. Treatment with an extracellular signal-regulated kinase inhibitor and p38 kinase inhibitor attenuated TGF-β1-induced AQP3 expression in HPMCs. These data suggest that TGF-β1 induces AQP3 and that AQP3 has a critical role in TGF-β-induced HPMC migration. These findings provide evidence of a novel role for AQP3 in peritoneal fibrosis and wound healing. The effect of TGF-β1 on AQP3 expression in HPMCs is mediated, at least in part, by ERK and p38 signaling.

Not Early Referral but Planned Dialysis Improves Quality of Life and Depression in Newly Diagnosed End Stage Renal Disease Patients: A Prospective Cohort Study in Korea

Background Health-related quality of life (HRQOL) has recently become an important issue. It reportedly affects morbidity and mortality in patients with end-stage renal disease (ESRD). In this study, we investigated whether early referral and planned dialysis improve the HRQOL and depression of patients with ESRD. Methods We prospectively enrolled newly diagnosed patients with ESRD, from 31 hospitals in Korea, who completed questionnaires at 3 months after dialysis. We also got follow-up survey at 1 year after dialysis. To measure HRQOL and depression, Kidney Disease Quality of Life Short Form 36 (KDQOL-36) and Beck’s Depression Inventory (BDI) were utilized. Results A total of 643 patients were analyzed. Referral type did not affect either KDQOL-36 or BDI scores. However, the planned dialysis group showed significantly better scores in 4 of 5 KDQOL-36 domains than did the unplanned group at 3 months after dialysis and partly, the effect was sustained for 1 year after dialysis. The benefit of planned dialysis was significant after adjusting for age, sex, type of dialysis, marital status, educational attainment, occupation, modified Charlson comorbidity index, albumin, and hemoglobin levels. BDI scores were also lower which indicate less depressive mood in planned dialysis group than those in unplanned group both at 3 months and 1 year after dialysis. Conclusions Not early referral but planned dialysis improved both the short- and long-term HRQOL and depression of patients with ESRD. Nephrologists should try to help patients to initiate dialysis in a planned manner.

Nafamostat Mesilate as an Anticoagulant During Continuous Renal Replacement Therapy in Patients With High Bleeding Risk: A Randomized Clinical Trial.

AbstractNafamostat mesilate (NM), a synthetic serine protease inhibitor, has been used increasingly as an anticoagulant during continuous renal replacement therapy (CRRT). However, there, are limited data from randomized studies on NM use in patients with a bleeding tendency. This prospective study evaluated the efficacy and safety of NM use during CRRT in patients with acute kidney injury (AKI) patients at high risk of bleeding.Patients with AKI at high risk of bleeding were randomized into the NM and no anticoagulant (NA) groups. The primary outcome was the treatment efficacy represented by the filter lifespan. Several parameters, including safety and patient survival rates at 30 and 90 days, were analyzed as secondary outcomes.Fifty-five patients were included in this study (NM group = 31, NA group = 24). The baseline characteristics did not significantly differ between the groups. The mean filter lifespan was significantly longer in the NM group than in the NA group (31.7 ± 24.1 versus 19.5 ± 14.9 hours; P = 0.035). The most common cause of filter failure was filter clotting, which was significantly more frequent in the NA group than in the NM group (59.6% versus 37.7%, P = 0.024). The Cox proportional hazards model showed a 42.2% longer filter lifespan in the NM group compared with the NA group (hazard ratio, 0.578; 95% confidence interval, 0.362–0.923; P = 0.022). There were no significant differences in the frequencies of transfusions and major bleeding between the groups. Patient survival rates at 30 and 90 days after CRRT initiation were comparable between the groups.Nafamostat mesilate is a safe and effective anticoagulant for CRRT and allows sufficient filter survival without increasing the risk of bleeding in critically ill patients with AKI and bleeding tendencies.