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.

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.).

Bioimpedance spectroscopy-guided fluid management in peritoneal dialysis patients with residual kidney function: A randomized controlled trial.

AIM: Bioimpedance spectroscopy (BIS) allows volume status to be assessed objectively. This study evaluated the effect of BIS-guided fluid management on residual kidney function (RKF), volume status, and cardiovascular events in peritoneal dialysis (PD) patients. METHODS: A multicenter, prospective, randomized, controlled trial was conducted over 12 months in 2013-2017. Non-anuric PD patients (urine volume ≥ 500 mL/day) were randomized to clinical method-guided management (n = 98) or BIS-guided management (n = 103). The volume in the BIS group was controlled with BIS, with the aim of achieving the target overhydration (OH) goal of -2.0 to +2.0 L. The volume in the control group was controlled by clinical assessment alone. The groups were compared in terms of change in RKF and volume status at 12 months relative to baseline and in terms of cardiovascular event rates during a median follow-up period of 36 months. RESULTS: Compared with the controls, the BIS group did not show a significant improvement in change in OH, after adjustments were made for covariates (P = 0.191). The two groups did not differ in terms of delta OH, renal creatinine and urea clearance, and 24 h urine volume. The control and BIS groups also did not differ significantly in terms of change in peritoneal ultrafiltration volume, blood pressure, body weight and echocardiographic variables or in cardiovascular event rates (10.2% vs 11.3%; P = 0.953). CONCLUSION: Bioimpedance spectroscopy-guided fluid management did not show an additional benefit to achieve euvolemia, and did not affect the decline in RKF in non-anuric PD patients.

Safety and Efficacy of Tolvaptan in Korean Patients with Hyponatremia Caused by the Syndrome of Inappropriate Antidiuretic Hormone.

BACKGROUND: The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). METHODS: Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 ± 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4. RESULTS: Serum sodium increased significantly from baseline during the first 24 hours (126.8 ± 4.3 vs. 133.7 ± 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 ± 3.8 vs. 135.6 ± 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 ± 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = -0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 ± 4.8 mmol/L) than in moderate (6.4 ± 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 ± 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775-0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500-0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected. CONCLUSION: TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV.

Influence of frailty on health-related quality of life in pre-dialysis patients with chronic kidney disease in Korea: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) is a progressive and lifelong condition with multiple medical comorbidities. Patients with CKD experience frailty more frequently and have lower health-related quality of life than do those with other chronic diseases. The purpose of this study was to examine the prevalence of frailty and investigate the contribution of frailty to quality of life in pre-dialysis CKD patients in Korea. METHODS: Using a cross-sectional survey design, data were collected at an outpatient CKD clinic in a general hospital in Korea. The frailty criterion was modified from previous studies. The Short Form-36 Health Survey version 2 was used to measure physical and mental component summary scores. Data were analyzed using chi-square, t-tests, and hierarchical linear regression. RESULTS: Of the 168 CKD patients, 63 (37.5 %) were frail. Frail patients were significantly older and had lower physical and mental quality of life than those who were non-frail. In hierarchical regression evaluating the influence of frailty on physical and mental quality of life, the initial model was significantly improved when frailty was included. Frail patients had lower physical and mental quality of life. CONCLUSIONS: Frailty affected both physical and mental quality of life in pre-dialysis patients with CKD. More attention should be paid to the potential role of early detection and prevention of frailty to improve patients' quality of life.

Is the new GFR equation using inulin clearance a more accurate method for Asian patients?

Recently, a new glomerular filtration rate (GFR) equation for the Japanese population was proposed using measured inulin clearance. To expand its applicability to other Asian populations, we performed a comparative study in the Korean population. Inulin clearance was measured in 166 patients from seven participating medical centers in Korea. Patient's sera and urine were collected, and baseline clinical characteristics were measured to provide an estimated GFR (eGFR) by the Japanese GFR equation using inulin clearance (Japanese-GFR equation), the Modification of Diet in Renal Disease (MDRD) study equation, and the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) equation. We compared the results to determine which equation best estimated the measured GFR (mGFR). Accuracy (95% CI) within 30% of mGFR by the Japanese-GFR equation, the CKD-EPI equation and the MDRD study equation were 66 (58 - 72), 51 (43 - 58), and 55 (47 - 62)%, respectively. Bias (mGFR minus eGFR) were 3.4 ± 22.4, -12.0 ± 22.1, and -9.7 ± 23.8 mL/min/1.73 m2, respectively. The accuracy of the Japanese-GFR equation was significantly better than MDRD study equation in subjects with mGFR < 60 mL/min/1.73 m2 and in total subjects. The bias of the Japanese-GFR equation was significantly smaller compared with other two equations in total subjects. The Japanese-GFR equation has a higher accuracy with less bias than the other equations in estimating GFR in Korean populations. Further studies are required to determine if the current Japanese-GFR equation could represent the standard eGFR for other Asian populations.

Effect of conversion from ESA with shorter half-life to CERA once monthly for maintaining Hb concentration in pre-dialysis CKD patients.

BACKGROUND: The purpose of this study is to identify whether hemoglobin (Hb) concentrations can be maintained, and to investigate changes in biomarkers, when switching from erythropoietin stimulating agents (ESA) with shorter half-life to once-monthly subcutaneous methoxy polyethylene glycol-epoetin ß (CERA) in pre-dialysis chronic kidney disease (CKD) patients. METHODS: Pre-dialysis CKD patients (n=191) aged ≥18 years who maintained their Hb level 10-12 g/dL through use of epoetin-α, epoetin-ß, or darbepoetin-α were enrolled. Hb levels and CERA dose was assessed prospectively for 24 weeks. Serum biomarkers related to coagulation, endothelial function, and iron metabolism were measured at weeks 0 and 24. RESULTS: Baseline Hb concentration was 10.8±0.6 g/dL Twelve and 24 weeks after conversion, mean Hb levels were 11.9±0.9 and 11.2±0.9 g/dL, respectively. The mean monthly CERA dose required to maintain Hb levels was gradually reduced. Of total 387 dose adjustments, dose increases and decreases occurred in 35 (9.0%) and 352 (91.0%) episodes, respectively. Hb overshoot occurred in 14 (9.7%) patients. P-selectin was significantly decreased, whereas VCAM was significantly increased 24 weeks after conversion (P < 0.05). Serum soluble transferrin receptor E-selectin and prohepcidin levels were similar before and after switching to CERA (P=N-S). CONCLUSION: Conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients can efficaciously maintain Hb. The CERA dose requirement decreased significantly. The conversion ratio may need to be reduced when switching from ESA with shorter half-life to CERA. CERA may change biomarkers associated with platelet reactivity and endothelial microenvironment.

Effect of lanthanum carbonate on phosphate control in continuous ambulatory peritoneal dialysis patients in Korea: a randomized prospective study.

BACKGROUND: Hyperphosphatemia is a common complication in end-stage renal disease (ESRD) patients. Reducing the serum phosphate level is crucial in management of ESRD. METHODS: This study was a randomized prospective study, designed to compare patients with hyperphosphatemia undergoing peritoneal dialysis while taking lanthanum carbonate or calcium carbonate. We divided 72 continuous ambulatory peritoneal dialysis (CAPD) patients whose serum phosphate levels were over 5.6 mg/dl into two groups to receive either lanthanum carbonate or calcium carbonate. Serum calcium, phosphate and PTH levels were examined serially for 24 weeks. RESULTS: Both lanthanum carbonate and calcium carbonate reduced serum phosphate levels, from 6.79 ± 1.05 to 5.44 ± 1.44 and from 6.31 ± 1.13 to 4.74 ± 0.78 mg/dl, respectively. The calcium × phosphate product level was reduced in the lanthanum carbonate and calcium carbonate groups from 60.23 ± 10.23 to 46.97 ± 16.42 and from 57.92 ± 11.05 to 44.50 ± 7.74 mg2/dl2, respectively. The serum parathyroid hormone (PTH) level in the lanthanum carbonate group did not change significantly compared to baseline during the study, but in the calcium carbonate group, the serum PTH level decreased significantly. Gastrointestinal complications were the main adverse effects of lanthanum carbonate and 11 out of 35 patients dropped out of the study due to this complication. CONCLUSIONS: Lanthanum carbonate was as effective as calcium carbonate in reducing serum phosphate level, and serum PTH level tended to be steadier in the lanthanum carbonate group compared to the calcium carbonate group. Though the ifference was not significant, lanthanum carbonate tended not to elevate serum calcium level in CAPD patients compared to calcium carbonate. The high incidence of gastrointestinal adverse effect in the lanthanum carbonate group will need further evaluation.

Human erythropoietin gene delivery using an arginine-grafted bioreducible polymer system.

Erythropoiesis-stimulating agents are widely used to treat anemia for chronic kidney disease (CKD) and cancer, however, several clinical limitations impede their effectiveness. Nonviral gene therapy systems are a novel solution to these problems as they provide stable and low immunogenic protein expression levels. Here, we show the application of an arginine-grafted bioreducible poly(disulfide amine) (ABP) polymer gene delivery system as a platform for in vivo transfer of human erythropoietin plasmid DNA (phEPO) to produce long-term, therapeutic erythropoiesis. A single systemic injection of phEPO/ABP polyplex led to higher hematocrit levels over a 60-day period accompanied with reticulocytosis and high hEPO protein expression. In addition, we found that the distinct temporal and spatial distribution of phEPO/ABP polyplexes contributed to increased erythropoietic effects compared to those of traditional EPO therapies. Overall, our study suggests that ABP polymer-based gene therapy provides a promising clinical strategy to reach effective therapeutic levels of hEPO gene.

Effects of neutral pH and low-glucose degradation product-containing peritoneal dialysis fluid on systemic markers of inflammation and endothelial dysfunction: a randomized controlled 1-year follow-up study.

BACKGROUND: The local peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) have been extensively described. However, the systemic effects of prolonged prescription of these solutions are unknown. This study aimed to evaluate the effects of neutral pH and low-GDP PDF on systemic inflammation and endothelial dysfunction markers in peritoneal dialysis (PD) patients. METHODS: This is a multicenter, open labeled, randomized controlled trial including one hundred fifty-two patients initiating continuous ambulatory peritoneal dialysis for end-stage renal disease from seven centers in Korea. Participants were randomly allocated to conventional PDF (Stay safe®; Fresenius Medical Care, Bad Homburg, Germany) or low-GDP PDF (Balance®; Fresenius Medical Care) and were followed for 1 year. Primary outcome variable was the inflammation and endothelial dysfunction index (IEDI), a composite score derived from serum levels of soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cellular adhesion molecule (sVCAM)-1 and high-sensitivity C-reactive protein (hs-CRP). sICAM-1, sVCAM-1, residual renal function (RRF), peritoneal membrane transport characteristics, ultrafiltration volume and nutritional parameters were measured as secondary outcome variables. RESULTS: Of 152 patients randomized, 146 (low-GDP: conventional PDF, 79:67) patients entered the trial (46% male, 53% with diabetes mellitus). At 12-month follow-up, the low-GDP group had significantly lower levels of IEDI, sICAM-1 and sVCAM-1 compared to the conventional group; hs-CRP was not different between groups. Peritoneal transport characteristics, RRF, nutritional parameters, incidence of peritonitis and death-censored technique survival were not different between groups. CONCLUSION: Neutral pH and low-GDP PDF likely produce fewer changes in markers of endothelial dysfunction compared to conventional PDF in incident PD patients.

Immunogenicity of recombinant human erythropoietin in Korea: a two-year cross-sectional study.

Immunogenicity of erythropoietin (EPO) is related with pure red cell aplasia (PRCA). We sought to determine the prevalence of antibody (Ab)-mediated PRCA in Korea and threshold diagnostic criteria by dual parameters: Ab titer and neutralizing activity. This study was a multi-center, cross-sectional study for two years. In the first year study (1 YS), 209 samples suspected to be EPO resistance were collected. In the second year study (2 YS), all the patients who consented to participate (N = 946) were enrolled. In 1 YS, we found three and six serum samples that were positive and borderline for anti-EPO Abs, respectively. The first three patients had neutralizing activity (NT) and were diagnosed as PRCA. In 2 YS, seven patients were anti-EPO positives and six had borderline levels. Among them, one patient with NT was diagnosed as PRCA and one with NT as aplastic anemia. The prevalence of PRCA was 0.106%. The correlation analysis of the 22 patients who had anti-EPO Ab showed that dual crossed cut-off lines (anti-EPO Ab titer ≥ 40 ng/ml, % NT ≥ 25%) were able to clearly isolate red cell aplasia. We suggest novel diagnostic criteria for diagnosis and prediction of Ab-mediated PRCA with data from both Ab titer assays and NT bioassays.

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.

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.

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.

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.

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 dialysis modality on arterial stiffness in patients with end-stage renal disease.

BACKGROUND: Arterial stiffness determined by brachial-ankle pulse wave velocity (baPWV) has been established as a powerful predictor of cardiovascular mortality in hemodialysis (HD) patients. There are, however, few studies regarding the comparative impact of different renal replacement therapies (RRTs) on PWV. Therefore, we conducted a cross-sectional study to compare arterial wall properties and cardiac function between patients treated with continuous ambulatory peritoneal dialysis (CAPD) and those with HD who were matched for age, dialysis duration, and blood pressure. METHODS: baPWV and transthoracic echocardiography (TTE) were performed in HD patients (n = 23) after 1 h of midweek dialysis session and CAPD patients (n = 26) with empty abdomen after drainage of dialysate. The baseline data were retrospectively reviewed. RESULTS: baPWV was significantly higher in HD patients than in CAPD patients (18.1 +/- 2.8 vs. 16.1 +/- 2.7 m/s, p = 0.015). TTE revealed significantly increased E/E', left atrial volume index (LAVI), and inferior vena cava (IVC) diameter index in HD patients compared with CAPD patients (p < 0.05). In a multivariate regression analysis adjusted for dialysis modality, age, systolic BP, residual glomerular filtration rate, diabetes, and echocardiographic parameters, HD was independently associated with increased baPWV. CONCLUSION: This study showed that HD patients had significantly increased arterial stiffness and severe diastolic dysfunction compared with CAPD patients.

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.

Prognostic value of elevated cardiac troponin I in ESRD patients with sepsis.

BACKGROUND: Elevated cardiac troponin (cTn) levels have been reported to predict adverse cardiovascular outcomes in asymptomatic ESRD patients. However, the prognostic value of elevated cTn levels associated with sepsis in ESRD patients is unknown. Therefore, this study aimed to elucidate the clinical implications of elevated cTnI levels in ESRD patients with sepsis. METHODS: Of the 305 ESRD patients in whom cTnI was measured between January 2003 and December 2005, sepsis developed in 121 patients during follow-up. Based on cTnI levels at the onset of sepsis, patients were classified as elevated cTnI group (ET, n = 50, >0.2 ng/ml) and lower cTnI group (LT, n = 71, < or =0.2 ng/ml). Study endpoints were short- and long-term mortality. Short-term mortality was defined as death occurring within 90 days after sepsis, and patients who survived during this period were followed till death after 90 days. RESULTS: Before sepsis, the median concentration of cTnI was 0.05 (0.01-3.59) ng/ml and it was significantly increased to 0.11 (0.01-22.0) ng/ml when sepsis supervened (P < 0.01). Compared to the LT group, the short-term mortality rate was significantly higher in the ET group (P < 0.05). After adjustment for age, diabetes, serum albumin and CRP levels, presence of shock and previous cardiovascular disease history, the ET group had a greater odds ratio of short-term mortality (OR 5.13, P < 0.01). In addition, the Kaplan-Meier plot for long-term survival revealed a significantly higher mortality rate in the ET group. In a multivariate Cox regression analysis, the elevation of cTnI levels was an independent determinant for long-term mortality (HR 5.90, P < 0.01). CONCLUSION: This study showed that elevated cTnI levels were significantly associated with short- and long-term mortality in ESRD patients with sepsis. Therefore, elevated cTnI levels in these patients should not be overlooked and be followed for adverse outcomes.