Chronic kidney disease in nonalcoholic fatty liver disease at primary healthcare centers in Korea.

BACKGROUND: The prevalence rates of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are expected to increase with the rising trends in diabetes and obesity associated with aging populations. Considering the impacts of coexistent NAFLD and CKD on morbidity and mortality rates, screening strategies for groups at high-risk of CKD are needed in community-dwelling individuals with NAFLD. The aims of this study were to determine the prevalence and distribution of CKD in NAFLD, as well as the risk factors for CKD and the correlation with liver fibrosis in asymptomatic individuals with NAFLD at primary healthcare centers in Korea. METHODS: This retrospective cross-sectional study used data from 13 health-promotion centers in 10 Korean cities. Liver steatosis and stiffness were assessed using ultrasonography and magnetic resonance elastography (MRE), respectively. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2, and urine albumin-to-creatinine ratio or proteinuria. CKD was categorized into four stages: no CKD, mild, moderate, and severe. Comparisons according to the CKD stages in NAFLD were performed using Student's t-test or the chi-square test. Multivariable logistic regression analyses were performed to identify the risk factors for CKD and the correlation with liver fibrosis in NAFLD. RESULTS: The prevalence of CKD was 12.4% in NAFLD. Albuminuria (16.2%) and proteinuria (8.0%) were more prevalent in NAFLD. NAFLD (odd ratio = 1.27, 95% CI = 1.09-1.48, P = 0.003) was independently associated with CKD of at least mild stage. However, there was no significant association between CKD of at least moderate stage and NAFLD after adjusting for age and a metabolically unhealthy status. CKD was associated with significant liver fibrosis as measured by MRE in NAFLD. CONCLUSION: The presence of NAFLD and liver fibrosis were independent risk factors for CKD, but NAFLD was not an independent risk factor for the later stages of CKD.

Why should we focus on high-volume hemodiafiltration?

Though noticeable technological advances related to hemodialysis (HD) have been made, unfortunately, the survival rate of dialysis patients has yet to improve significantly. However, recent research findings reveal that online hemodiafiltration (HDF) significantly improves patient survival in comparison to conventional HD. Accordingly, the number of patients receiving online HDF is increasing. Although the mechanism driving the benefit has not yet been fully elucidated, survival advantages are mainly related to the lowering of cardiovascular mortality. High cardiovascular mortality among HD patients is seemingly attributable to the cardiovascular changes that occur in response to renal dysfunction and the HD-induced myocardial stress and injury, and online HDF appears to improve such secondary cardiovascular changes. Interestingly, patient survival improves only if the convection volume is supplied sufficiently over a certain level during online HDF treatment. In other words, survival improvement from online HDF is related to convection volume. Therefore, there is a growing interest in high-volume HDF in terms of improving the survival rate. The survival improvement will require a minimum convection volume of 23 L or more per 4-hour session for postdilution HDF. To obtain an optimal high convection volume in online HDF, several factors, such as the treatment time, blood flow rate, filtration fraction, and dialyzer, need to be considered. High-volume HDF can be performed easily and safely in routine clinical practice. Therefore, when the required equipment is available, performing high-volume HDF will help to improve the survival rate of dialysis patients.

Sleep apnea is associated with residual kidney function and mortality in patients with peritoneal dialysis: Prospective cohort study.

INTRODUCTION: Fluid overload and sleep apnea (SA) are known risk factors for mortality in dialysis patients. Although incidence and severity of SA were shown higher in peritoneal dialysis (PD) patients than in hemodialysis patients, data regarding the association of SA with body fluid status and mortality are limited. Therefore, the association of SA with body fluid status and mortality were investigated in a prospective cohort with patients undergoing PD. METHODS: The present study included 103 prevalent PD patients who were followed up for median 70 months. At baseline, the subjects underwent in-home polysomnography, bioelectrical impedance analysis, and urea kinetics. Excessive daytime sleepiness and sleep quality were assessed using sleep questionnaires. SA was defined as apnea/hypopnea index higher than 15 events per hour. RESULTS: Sleep apnea was diagnosed in 57 (55.3%) patients (SA group); the subjects had significantly higher extracellular water (10.3 ± 1.4 vs. 9.2 ± 1.8, p = 0.001) and lower residual kidney function (RKF) (3.3 ± 3.3 vs. 5.9 ± 7.2, p = 0.02) compared with subjects in the non-SA group. SA was significantly associated with RKF [odds ratio, 0.84; 95% confidence interval (CI), 0.73-0.97] in multivariable logistic regression analysis. In multivariable Cox regression models, SA was a significant predictor of mortality in PD patients (adjusted hazard ratio, 5.74; 95% CI, 1.09-30.31) after adjusting for well-known risk factors. CONCLUSIONS: Sleep apnea was very common in PD patients and significantly associated with lower RKF. SA was also a novel risk predictor of mortality in PD patients.

Roxadustat for CKD-related Anemia in Non-dialysis Patients.

INTRODUCTION: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and improves iron metabolism. We assessed the efficacy and tolerability of roxadustat in patients with chronic kidney disease (CKD)-related anemia not on dialysis. METHODS: ANDES was a global Phase 3 randomized study in which adults with stage 3-5 CKD not on dialysis received roxadustat or placebo. Patients were initially dosed thrice weekly; dose was titrated to achieve a hemoglobin level ≥11.0 g/dl, followed by titration for maintenance. The primary endpoints were change in hemoglobin (weeks 28-52) and proportion of patients achieving a hemoglobin response (hemoglobin ≥11.0 g/dl and increase ≥1.0 g/dl [baseline >8.0 g/dl], or increase ≥2.0 g/dl [baseline ≤8.0 g/dl]) (week 24). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were recorded. RESULTS: In roxadustat (n = 616) and placebo (n = 306) groups, hemoglobin mean (SD) change from baseline over weeks 28-52 was significantly larger for roxadustat (2.00 [0.95]) versus placebo (0.16 [0.90]), corresponding to least-squares mean difference of 1.85 g/dl (95% confidence interval [CI] 1.74-1.97; P < 0.0001). The proportion of patients achieving a response at week 24 was larger for roxadustat (86.0%; 95% CI 83.0%-88.7%) versus placebo (6.6%; 95% CI 4.1%-9.9%; P < 0.0001). The proportion of patients receiving rescue therapy at week 52 was smaller for roxadustat (8.9%) versus placebo (28.9%); hazard ratio, 0.19 (95% CI 0.14-0.28; P < .0001). The incidences of TEAEs and TESAEs were comparable. CONCLUSION: This study showed that roxadustat corrected and maintained hemoglobin and was well tolerated in patients with CKD-related anemia not on dialysis (ClinicalTrials.gov NCT01750190).

The impact of volume overload on technique failure in incident peritoneal dialysis patients.

BACKGROUND: Technique failure in peritoneal dialysis (PD) can be due to patient- and procedure-related factors. With this analysis, we investigated the association of volume overload at the start and during the early phase of PD and technique failure. METHODS: In this observational, international cohort study with longitudinal follow-up of incident PD patients, technique failure was defined as either transfer to haemodialysis or death, and transplantation was considered as a competing risk. We explored parameters at baseline or within the first 6 months and the association with technique failure between 6 and 18 months, using a competing risk model. RESULTS: Out of 1092 patients of the complete cohort, 719 met specific inclusion and exclusion criteria for this analysis. Being volume overloaded, either at baseline or Month 6, or at both time points, was associated with an increased risk of technique failure compared with the patient group that was euvolaemic at both time points. Undergoing treatment at a centre with a high proportion of PD patients was associated with a lower risk of technique failure. CONCLUSIONS: Volume overload at start of PD and/or at 6 months was associated with a higher risk of technique failure in the subsequent year. The risk was modified by centre characteristics, which varied among regions.

The impact of prophylactic ureteral stenting during kidney transplantation on postoperative surgical outcomes.

Background: The aim of this study was to evaluate the safety and feasibility of prophylactic ureteric stenting during kidney transplantation (KT). Methods: The authors retrospectively reviewed patients who underwent KT between June 2016 and June 2019. The prophylactic ureteral stenting group (double-J [DJ]) and no-stent group (no-DJ) were compared with respect to the clinical data and surgical outcomes. Results: A total of 42 patients underwent KT; 17 patients were classified into the DJ group and 25 patients into the no-DJ group. Antithymocyte globulin induction and donor-specific antibody positivity were significantly higher in the DJ group. There were no significant differences between the groups in terms of symptomatic urinary tract infection (UTI). The time to postoperative UTI was significantly shorter in the DJ group than in the no-DJ group (33.5±7.8 vs. 105.3±71.6 days, P=0.013). The development of postoperative BK viremia was significantly higher in the no-DJ group (0.0% vs. 16.0%, P=0.035). Urologic complications were significantly higher in the no-DJ group (0.0% vs. 16.0%, P=0.035). In the no-DJ group, urologic complications occurred in four patients ureteroneocystostomy stenosis in three patients and ureteroneocystostomy leakage in one patient. Percutaneous ureteral interventions were performed for all patients using percutaneous nephrostomy and reno-uretero-vesical stenting. However, there were no postoperative urologic complications in the DJ group. Conclusions: Prophylactic ureteric stenting during KT may be safe and feasible without significantly increasing the incidence of UTI and BK viremia. Additionally, prophylactic ureteric stenting may reduce urologic complications after KT.

New oral spherical carbon adsorbent effectively reduces serum indoxyl sulfate levels in moderate to advanced chronic kidney disease patients: a multicenter, prospective, open-label study.

BACKGROUND: Elevated levels of serum indoxyl sulfate (IS) have been linked to cardiovascular complications in patients with chronic kidney disease (CKD). Oral sorbent therapy using spherical carbons selectively attenuates IS accumulation in CKD patients. This study aimed to investigate whether oral administration of a new oral spherical carbon adsorbent (OSCA), reduces serum IS levels in moderate to severe CKD patients. METHODS: This prospective, multicenter, open-label study enrolled patients with CKD stages 3-5. Patients were prescribed OSCA for 8 weeks (6 g daily in 3 doses) in addition to standard management. Serum IS levels were measured at baseline and 4 and 8 weeks of treatment with OSCA. RESULTS: A total of 118 patients were enrolled and 87 eligible patients completed 8 weeks of study. The mean age of the study subjects was 62.8 ± 13.7 years, and 80.5% were male. Baseline levels of serum IS were negatively correlated with estimated glomerular filtration rate (eGFR) (r = - 0.406, P < 0.001) and increased with increasing CKD stages (stage 3, 0.21 ± 0.21 mg/dL; stage 4, 0.54 ± 0.52 mg/dL; stage 5, 1.15 ± 054 mg/dL; P for trend = 0.001). The patients showed significant reduction in serum total IS levels as early as 4 weeks after OSCA treatment (22.5 ± 13.9% reduction from baseline, P < 0.001) and up to 8 weeks (31.9 ± 33.7% reduction from baseline, P < 0.001). This reduction effect was noted regardless of age, kidney function, or diabetes. No severe adverse effects were reported. Gastrointestinal symptoms were the most commonly reported adverse effects. In total, 21 patients withdrew from the study, with dyspepsia due to heavy pill burden as the most common reason. The medication compliance rate was 84.7 ± 21.2% (min 9%, max 101%) for 8 weeks among those who completed the study. CONCLUSIONS: OSCA effectively reduced serum IS levels in moderate to severe CKD patients. Gastrointestinal symptoms were the most commonly reported complications, but no treatment-related severe adverse effects were reported. TRIAL REGISTRATION: Clinical Research Information Service ( KCT0001875 . 14 December 2015.).

Efficacy and safety of sodium zirconium cyclosilicate for hyperkalaemia: the randomized, placebo-controlled HARMONIZE-Global study.

AIMS: Sodium zirconium cyclosilicate (SZC, formerly ZS-9) is a selective K+ binder to treat adults with hyperkalaemia. HARMONIZE-Global examined the efficacy and safety of SZC among outpatients with hyperkalaemia from diverse geographic and ethnic origins. METHODS AND RESULTS: This phase 3, randomized, double-blind, placebo-controlled study recruited outpatients with serum K+ ≥5.1 mmol/L (measured by point-of-care i-STAT device) at 45 sites in Japan, Russia, South Korea, and Taiwan. Following open-label treatment with thrice-daily SZC 10 g during a 48 h correction phase (CP), patients achieving normokalaemia (K+ 3.5-5.0 mmol/L) were randomized 2:2:1 to once-daily SZC 5 g, SZC 10 g, or placebo during a 28 day maintenance phase (MP). The primary endpoint was mean central-laboratory K+ level during days 8-29 of the MP. Of 267 patients in the CP, 248 (92.9%) entered the MP. During the CP, mean central-laboratory K+ was reduced by 1.28 mmol/L at 48 h vs. baseline (P < 0.001). During the MP (days 8-29), SZC 5 and 10 g once-daily significantly lowered mean central-laboratory K+ by 9.6% and 17.7%, respectively, vs. placebo (P < 0.001 for both). More patients had normokalaemia (central-laboratory K+ 3.5-5.0 mmol/L at day 29) with SZC 5 (58.6%) and 10 g (77.3%) vs. placebo (24.0%), with the greatest number of normokalaemic days in the 10-g group. The most common adverse events with SZC were mild or moderate constipation and oedema. CONCLUSIONS: Normokalaemia achieved during the CP was maintained over 28 days with SZC treatment among outpatients with hyperkalaemia.

Efficacy and Safety of CKD-11101 (Proposed Biosimilar of Darbepoetin-Alfa) Compared with Darbepoetin-Alfa in Patients on Hemodialysis: A Randomized, Double-Blinded, Parallel-Group Phase III Study.

BACKGROUND: Darbepoetin-alfa is an erythropoiesis-stimulating agent (ESA) with a long elimination half-life that achieves better hemoglobin (Hb) stability than short-acting ESAs. OBJECTIVE: We aimed to evaluate the efficacy and safety of intravenous CKD-11101 (a biosimilar of darbepoetin-alfa) compared with those of darbepoetin-alfa in hemodialysis patients. METHODS: The study was performed in 24 centers in Korea between June 2015 and June 2017. The study subjects were randomized in a double-blind manner. The follow-up duration was 24 weeks, which consisted of 20 weeks of maintenance and 4 weeks of evaluation period. All patients underwent a stabilization period to achieve a target baseline Hb of 10-12 g/dL before randomization. Following randomization, patients received darbepoetin-alfa or CKD-11101 weekly or biweekly. RESULTS: A total of 403 patients were randomized into two groups, and a total of 325 patients (80.6%) completed the investigation. The differences between the two groups in terms of change in the average Hb level from baseline to evaluation were not significant. The average administered dose of ESA was similar between the groups. There was no difference in the proportion of patients who maintained the target Hb during the evaluation period [60.4% vs. 66.2% in the CKD-11101 and darbepoetin-alfa groups, respectively (p = 0.3038)]. In addition, the safety analysis, consisting of adverse events and adverse drug reactions, showed comparable results between the two groups. CONCLUSION: The changes in the level of Hb, dose of erythropoietin, and achievement rate of the target Hb during the study period were comparable between the groups. CKD-11101 has an equivalent efficacy and safety compared with darbepoetin-alfa in patients undergoing hemodialysis.

The Effect of Strict Volume Control Assessed by Repeated Bioimpedance Spectroscopy on Cardiac Function in Peritoneal Dialysis Patients.

Adequate fluid management plays an important role in decreasing cardiovascular risk in peritoneal dialysis (PD) patients. We evaluated whether strict volume control monitored by bioimpedance spectroscopy (BIS) affects cardiac function in PD patients. This study is a secondary analysis of a multicentre, prospective, randomized, controlled trial. Fluid overload was assessed by the average overhydration/extracellular water (OH/ECW) at baseline, 6 months and 12 months. Patients were categorized as time-averaged overhydrated (TA-OH/ECW ≥15%) or normohydrated (TA-OH/ECW <15%), and echocardiographic parameters were compared between groups. Among a total of 151 patients, 120 patients exhibited time-averaged normohydration. Time-averaged overhydrated patients had a significantly higher left atrial (LA) diameter and E/e' ratio and a lower left ventricular (LV) ejection fraction at 12 months than time-averaged normohydrated patients. LA diameter, end-systolic volume and end-diastolic volume were decreased at 12 months compared to baseline in time-averaged normohydrated patients only. TA-OH/ECW was independently associated with ejection fraction at 12 months (ß = -0.190; p = 0.010). TA-OH/ECW, but not OH/ECW at 12 months, was an independent risk factor for LV dysfunction (odds ratio 4.020 [95% confidence interval 1.285-12.573]). Overhydration status based on repeated BIS measurements is an independent predictor of LV systolic function in PD patients.