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Background: Pruritus is a common condition in chronic kidney disease (CKD), especially for patients receiving haemodialysis. CKD-associated pruritus (CKD-aP) can be distressing and have a negative impact on quality of life (QoL). This post hoc analysis aimed to assess the relationship between pruritus relief and QoL., Methods: Data from phase 3 trials [(NCT03422653, NCT03636269 grouped), and NCT03998163] of the novel antipruritic difelikefalin ( N  = 914) were used to assess the relationship between reductions in pruritus intensity at Week 12 (24-h Worst Itching Intensity Numeric Rating Scale; WI-NRS), perceived improvement in itch (Patient Global Impression of Change, PGI-C) and pruritus-related QoL (Skindex-10 questionnaire)., Results: Patients receiving difelikefalin had greater improvements in Skindex-10 total scores than those receiving placebo [LS mean treatment difference -3.4; 95% confidence interval (CI) -5.5, -1.3; P  = .002] and greater improvements across Skindex-10 domains (disease, mood and social functioning) at Week 12. In patients receiving difelikefalin, those with clinically meaningful improvements in pruritus (≥3-point reduction in WI-NRS score) at Week 12 had a greater improvement in Skindex-10 total score (mean difference 14.2; 95% CI 11.0, 17.3; P  < .001) and Skindex-10 domains than those with a <3-point reduction in WI-NRS score. Improvements in Skindex-10 total scores correlated with PGI-C., Conclusions: Improvements in pruritus intensity following 12 weeks of treatment with difelikefalin were associated with improvements in QoL. Larger improvements in Skindex-10 scores were seen in patients with a greater reduction in pruritus intensity, indicating that improvements in pruritus are associated with a range of factors, such as mood and social functioning, that affect pruritus-related QoL., Competing Interests: S.S. reports consulting fees from Almirall, Beiersdorf, Bellus Health, Cara Therapeutics, Inc., Celgene Corporation, Galderma Laboratorium, Galderma R&D, LEO Pharma, Menlo Therapeutics, Novartis, Sienna Biopharmaceuticals, Trevi Therapeutics and Vanda Pharmaceuticals; lecture fees from Sanofi; and is an investigator for Dermasence, Kiniksa, Menlo Therapeutics, Novartis and Trevi Therapeutics. S.F. reports receipt of grants from Cara Therapeutics, Inc. T.S., D.R. and I.M. are employees and shareholders of CSL Vifor. F.M. and W.W. are employees and shareholders of Cara Therapeutics, Inc. K.K.-Z. reports commercial honoraria and support from Abbott, AbbVie, Alexion, Amgen, AstraZeneca, Aveo, Chugai, DaVita, Fresenius, Genentech, Haymarket Media, Hospira, Kabi, Keryx, Novartis, Pfizer, Relypsa, Resverlogix, Sandoz, Sanofi, Shire, Vifor, UpToDate and ZS Pharma., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Sodium zirconium cyclosilicate (SZC) binds potassium and ammonium in the gastrointestinal tract. In addition to serum potassium reduction, Phase 2 trial data have shown increased serum bicarbonate with SZC, which may be clinically beneficial because maintaining serum bicarbonate ≥22 mmol/L preserves kidney function. This exploratory analysis examined serum bicarbonate and urea, and urine pH data from three SZC randomized, placebo-controlled Phase 3 studies among patients with hyperkalaemia [ZS-003 (n = 753), HARMONIZE (n = 258) and HARMONIZE-Global (n = 267)]., Methods: In all studies, patients received ≤10 g SZC 3 times daily (TID) for 48 h to correct hyperkalaemia, followed by randomization to maintenance therapy with SZC once daily (QD) versus placebo for ≤29 days among those achieving normokalaemia., Results: Significant dose-dependent mean serum bicarbonate increases from baseline of 0.3 to 1.5 mmol/L occurred within 48 h of SZC TID in ZS-003 (all P < 0.05), which occurred regardless of chronic kidney disease (CKD) stage. Similar acute increases in HARMONIZE and HARMONIZE-Global were maintained over 29 days. With highest SZC maintenance doses, patient proportions with serum bicarbonate <22 mmol/L fell from 39.4% at baseline to 4.9% at 29 days (P = 0.005) in HARMONIZE and from 87.9% to 70.1%, (P = 0.006) in HARMONIZE-Global. Path analyses demonstrated that serum urea decreases (but not serum potassium or urine pH changes) were associated with SZC effects on serum bicarbonate., Conclusions: SZC increased serum bicarbonate concentrations and reduced patient proportions with serum bicarbonate <22 mmol/L, likely due to SZC-binding of gastrointestinal ammonium. These SZC-induced serum bicarbonate increases occurred regardless of CKD stage and were sustained during ongoing maintenance therapy., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Real-world data for patients with chronic kidney disease (CKD), specifically pertaining to clinical management, metabolic control, treatment patterns, quality of life (QoL) and dietary patterns, are limited. Understanding these gaps using real-world, routine care data will improve our understanding of the challenges and consequences faced by patients with CKD, and will facilitate the long-term goal of improving their management and prognosis., Methods: DISCOVER CKD follows an enriched hybrid study design, with both retrospective and prospective patient cohorts, integrating primary and secondary data from patients with CKD from China, Italy, Japan, Sweden, the UK and the USA. Data will be prospectively captured over a 3-year period from >1000 patients with CKD who will be followed up for at least 1 year via electronic case report form entry during routine clinical visits and also via a mobile/tablet-based application, enabling the capture of patient-reported outcomes (PROs). In-depth interviews will be conducted in a subset of ∼100 patients. Separately, secondary data will be retrospectively captured from >2 000 000 patients with CKD, extracted from existing datasets and registries., Results: The DISCOVER CKD program captures and will report on patient demographics, biomarker and laboratory measurements, medical histories, clinical outcomes, healthcare resource utilization, medications, dietary patterns, physical activity and PROs (including QoL and qualitative interviews)., Conclusions: The DISCOVER CKD program will provide contemporary real-world insight to inform clinical practice and improve our understanding of the epidemiology and clinical and economic burden of CKD, as well as determinants of clinical outcomes and PROs from a range of geographical regions in a real-world CKD setting., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for the treatment of adults with hyperkalaemia. This post hoc analysis of an open-label, single-arm trial (NCT02163499) compared SZC efficacy and safety >12 months among outpatients with hyperkalaemia and Stages 4 and 5 chronic kidney disease (CKD) versus those with Stages 1-3 CKD., Methods: Adults with serum K+ ≥5.1 mmol/L (measured by point-of-care i-STAT device) received SZC 10 g three times daily for 24-72 h until normokalaemia (i-STAT K+ 3.5-5.0 mmol/L) was achieved [correction phase (CP)], followed by once daily SZC 5 g for ≤12 months [maintenance phase (MP)]. Here, patients were stratified by baseline estimated glomerular filtration rate (eGFR <30 or ≥30 mL/min/1.73 m2). Study endpoints included percent achieving normokalaemia during CP and MP, mean serum K+ and bicarbonate during MP, and adverse events (AEs)., Results: Of 751 patients enrolled, 289 (39%), 453 (60%) and 9 (1%) had baseline eGFR values of <30, ≥30 mL/min/1.73 m2 or missing, respectively. During the CP, 82% of patients achieved normokalaemia in both eGFR subgroups within 24 h, and 100 and 95% with baseline eGFR <30 and ≥30 mL/min/1.73 m2, respectively, within 72 h. Corresponding proportions with normokalaemia during the MP were 82 and 90% at Day 365, respectively. Mean serum K+ reduction from baseline during the CP was sustained throughout the MP and serum bicarbonate increased. AEs during the MP were more common in the eGFR <30 ≥30 mL/min/1.73 m2 subgroup., Conclusions: SZC corrects hyperkalaemia and maintains normokalaemia among outpatients regardless of the CKD stage., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Among patients with nondialysis-dependent chronic kidney disease (NDD-CKD) and iron-deficiency anemia (IDA), ferric citrate increases hemoglobin and iron parameters and reduces serum phosphate and fibroblast growth factor 23 (FGF23), a key phosphate-regulating hormone. We conducted post hoc analyses of a phase 3 trial to explore associations between iron replacement, serum phosphate changes and FGF23 regulation., Methods: We employed multivariable regression and longitudinal mixed-effects models to identify and confirm, respectively, whether baseline demographic and laboratory variables were associated with ferric citrate-induced changes in serum phosphate or FGF23 concentrations. We employed path analyses to determine whether changes in FGF23 concentrations were mediated via changes in serum phosphate and/or transferrin saturation (TSAT)., Results: We analyzed a total of 117 and 115 ferric citrate-treated and placebo-treated patients, respectively. At 16 weeks, ferric citrate significantly reduced serum phosphate versus placebo (P = 0.006) only among patients with elevated baseline serum phosphate (≥4.5 mg/dL) and did not reduce serum phosphate among patients with baseline serum phosphate within the population reference range. Ferric citrate reduced intact FGF23 and C-terminal FGF23 partially via changes in TSAT (for C-terminal FGF23) and serum phosphate (for intact FGF23) and partially via unknown/unmeasured mechanisms., Conclusions: Ferric citrate reduced serum FGF23 concentrations (partially via effects on serum phosphate and iron balance) and did not reduce serum phosphate among patients with baseline serum phosphate concentrations within the population reference range., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Teaching methods in most residency and fellowship programs have not yet addressed the challenges of rapid dissemination of new scientific information. Our Northwell nephrology fellowship program used the smartphone application WhatsApp ® to facilitate nephrology education. A qualitative study was conducted to explore perceptions of nephrology fellows and faculty using WhatsApp ® as a teaching tool., Methods: A WhatsApp ® messenger group called 'Northwell Renal Forum' was created in 2018, which included all eight fellows and seven selected faculty members. Multiple choice questions on various nephrology topics were posted, about one to two per week. Fellows responded at their leisure. After 7 months, data were analyzed following two 1-h focus groups (one for faculty and one for fellows). Focus groups were moderated by two qualitative researchers, unknown to the participants, who asked open-ended questions about the WhatsApp ® learning approach., Results: Faculty feedback was generally positive. Three major themes arose: control over learning material, comfort being fostered between faculty and fellows and faculty perceptions of fellows. The fellows also reported an overall positive experience. Control and comfort were themes again identified in this focus group. Fellows reported feeling control over which faculty member was in the group and when to respond to questions. Fellows also felt comfort from learning without pressure. Variety was the third theme that arose., Conclusion: Focus group evaluations elucidated the strengths of using WhatsApp ® , and the overall positive experience of both faculty and fellows. This inexpensive and easy-to-use tool can augment the learning of nephrology during fellowship., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Late-stage chronic kidney disease (LS-CKD) can be defined by glomerular filtration rate (GFR) 0-30 mL/min. It is a period of risk for medication discrepancies because of frequent hospitalizations, fragmented medical care, inadequate communication and polypharmacy. In this study, we sought to characterize medication discrepancies in LS-CKD., Methods: We analyzed all patients enrolled in Northwell Health's Healthy Transitions in LS-CKD program. All patients had estimated GFR 0-30 mL/min, not on dialysis. Medications were reviewed by a nurse at a home visit. Patients' medication usage and practice were compared with nephrologists' medication lists, and discrepancies were characterized. Patients were categorized as having either no discrepancies or one or more. Associations between patient characteristics and number of medication discrepancies were evaluated by chi-square or Fisher's exact test for categorical variables, and two-sample t -test or Wilcoxon text for continuous variables., Results: Seven hundred and thirteen patients with a median age of 70 (interquartile range 58-79) years were studied. There were 392 patients (55.0% of the study population) with at least one medication discrepancy. The therapeutic classes of medications with most frequently occurring medication discrepancies were cardiovascular, vitamins, bone and mineral disease agents, diuretics, analgesics and diabetes medications. In multivariable analysis, factors associated with higher risk of discrepancies were congestive heart failure [odds ratio (OR) 2.13; 95% confidence interval (CI) 1.44-3.16; P = 0.0002] and number of medications (OR 1.29; 95% CI 1.21-1.37; P < 0.0001)., Conclusions: Medication discrepancies are common in LS-CKD, affect the majority of patients and include high-risk medication classes. Congestive heart failure and total number of medications are independently associated with greater risk for multiple drug discrepancies. The frequency of medication discrepancies indicates a need for great care in medication management of these patients.

There is increasing recognition that chronic diseases are a major challenge for health delivery systems and treasuries. These are highly prevalent and costly diseases and frequency is expected to increase greatly as the population of many countries ages. Chronic kidney disease (CKD) has not received the same attention as other chronic diseases such as congestive heart failure; yet, the prevalence and costs of CKD are substantial. Greater recognition and support for CKD may require that the disease no longer be viewed as one continuous disease state. Early CKD stages require less complex care and generate lower costs. In contrast, late-stage CKD is every bit as complex and costly as other major chronic diseases. Health authorities may not recognize and fund CKD care appropriately until late-stage CKD is defined clearly as separate and distinct from earlier stages of disease. In this review, we describe the burden of chronic diseases, consider the challenges and barriers and propose processes to improve late-stage CKD care. In particular, we recommend the need for improved continuity of care, enhanced use of information technology, multidisciplinary care, timely referral to nephrologists, protocol use and improved patient engagement.

Iron deficiency is common among patients with advanced kidney disease, particularly those requiring hemodialysis. Intravenous iron is a convenient treatment to supplement iron and is widely used among hemodialysis patients. Its efficacy is well established that, with treatment, hemoglobin levels rise and erythropoiesis-stimulating agent dose requirements are reduced. However, the safety of intravenous iron with respect to patient-centered outcomes has not been adequately studied. A variety of studies have indicated potential safety concerns, but most have been of small numbers of patients and with end points studied that have unclear clinical relevance. In this study, issues related to iron toxicity are reviewed.

Background: Fractures are an important cause of morbidity in hemodialysis patients. Multiple advances in the treatment of mineral and bone disease in hemodialysis patients have occurred. The purpose of this study was to determine whether the rate of fractures in hemodialysis patients has changed over time., Methods: We studied US Renal Data System (USRDS) datasets to determine the rates of hospitalized fractures among hemodialysis patients. The primary outcome was incidence of fractures requiring hospitalization. The fracture rate per 1000 person-years was calculated by year from 1992 to 2009. The first 90 days after initiating dialysis were excluded from analysis., Results: The incidence of hip and vertebral fractures increased from 12.5 fractures per 1000 patient-years in 1992 to 25.3 per 1000 patient-years in 2004 (P < 0.0001). Arm and leg fractures increased from 3.2 per 1000 patient-years in 1992 to 7.7 per 1000 patient-years in 2009 (P < 0.0001). The greatest increase in hip and verterbral fracture rate was seen in white patients >65 years of age. After 2004, the incidence rate of these fractures stabilized and subtly declined, but did not decrease significantly., Conclusions: Fracture rates increased significantly in hemodialysis patients from 1992 to 2004, with most of the increase occurring in elderly white patients. Assessment of fracture risk and management in dialysis patients at greatest risk requires greater emphasis and further study.

Background: Physical (PCS) and mental (MCS) component summary scales of the Short Form 36 (SF-36) health survey are validated measures of quality of life (QOL) and functional status. We sought to evaluate the PCS and MCS in haemodialyis patients as compared to the general population and other chronic diseases., Methods: A cohort of 134 haemodialysis patients (mean age 60.9+/-14.3 years, males 63.4%, Caucasians 66.4%) was followed from January 1996 to December 1998 (mean follow up 14.5+/-5.7 months). SF-36 questionnaires were administered every 3 months and PCS and MCS were calculated. Results were compared to the general population and other chronic diseases. Correlators of PCS and MCS, change in QOL over time, and the correlators of this change were determined., Results: Mean PCS was 36.9+/-8.8 and mean MCS was 47+/-10.7. Compared to the general US population, these represent a decline of 8.7+/-0.8 for PCS (P<0.0001) and 2.7+/-0.8 for MCS (P<0.001). PCS and MCS in end-stage renal disease (ESRD) were lower than in most other chronic diseases studied. Univariate correlators of PCS in haemodialysis patients included age, male sex, haematocrit, serum albumin, and severity of comorbid cardiac and pulmonary illnesses. Multivariate analysis demonstrated independent correlators of PCS to be male sex, serum albumin and severity of comorbid cardiac and pulmonary diseases. Univariate as well as multivariate correlators of MCS included: serum albumin, KT/V(urea), and status living alone. A trend analysis revealed that both PCS and MCS tended to decline in the initial months of dialysis but stabilized over time. Status living alone was a significant predictor of improvement in MCS by univariate as well as multivariate analysis., Conclusions: Self assessed physical and mental health of haemodialysis patients is markedly diminished compared to the general population and other chronic diseases.