Course of Hyperkalemia in Patients on Hemodialysis.

Background: Evidence of longitudinal serum potassium (sK) concentrations in hyperkalemic hemodialysis patients is sparse.

Objective: These post hoc analyses of the placebo arm of the phase 3b DIALIZE study (NCT03303521) explored the course of hyperkalemia in hemodialysis patients receiving placebo.

Methods: In DIALIZE, 196 patients receiving hemodialysis three times weekly were randomized to placebo or sodium zirconium cyclosilicate 5 g starting dose once daily on nondialysis days for 8 weeks.

Potassium responses to sodium zirconium cyclosilicate in hyperkalemic hemodialysis patients: post-hoc analysis of DIALIZE.

Background: Sodium zirconium cyclosilicate (SZC) is an effective and well-tolerated treatment for hyperkalemia in maintenance hemodialysis patients. In post-hoc analyses of the phase 3b DIALIZE study, we examined the spectrum of potassium responses to SZC.

Methods: Post-hoc analyses with SZC and placebo included: the number of long interdialytic interval (LIDI) visits during the 4-week evaluation period where patients attained pre-dialysis serum potassium (sK) concentrations of 4.

Consensus-Based Recommendations for the Management of Hyperkalemia in the Hemodialysis Setting.

Hyperkalemia (serum K >5.0 mmol/L) is commonly observed among patients receiving maintenance hemodialysis and associated with increased risk of cardiac arrhythmias. Current international guidelines may not reflect the latest evidence on managing hyperkalemia in patients undergoing hemodialysis, and there is a lack of high-quality published studies in this area.

Treatment of anemia in difficult-to-manage patients with chronic kidney disease.

The management of anemia of chronic kidney disease (CKD) is often challenging. In particular, for patients with underlying inflammation, comorbid type 2 diabetes or cancer, those hospitalized, and recipients of a kidney transplant, the management of anemia may be suboptimal. Responsiveness to iron and/or erythropoiesis-stimulating agents, the mainstay of current therapy, may be reduced and the risk of adverse reactions to treatment is increased in these difficult-to-manage patients with anemia of CKD.

Clinical Management of Hyperkalemia.

Hyperkalemia is an electrolyte abnormality with potentially life-threatening consequences. Despite various guidelines, no universally accepted consensus exists on best practices for hyperkalemia monitoring, with variations in precise potassium (K) concentration thresholds or for the management of acute or chronic hyperkalemia. Based on the available evidence, this review identifies several critical issues and unmet needs with regard to the management of hyperkalemia.

Sodium zirconium cyclosilicate increases serum bicarbonate concentrations among patients with hyperkalaemia: exploratory analyses from three randomized, multi-dose, placebo-controlled trials.

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)].

Impact of chronic kidney disease and anemia on health-related quality of life and work productivity: analysis of multinational real-world data.

Background: Reductions in health-related quality of life (HRQoL) in patients with chronic kidney disease (CKD) are thought to be exacerbated by the low hemoglobin (Hb) levels that define anemia, a common complication of CKD. The current analysis evaluated the impact of anemia on HRQoL and work productivity in patients with non-dialysis dependent and dialysis-dependent CKD using real-world data.

Methods: Data were collected in France, Germany, Italy, Spain, the UK, the USA and China in 2012-2018 in the Adelphi Real World Disease Specific Programme™ for CKD, a large, cross-sectional, survey of physicians and their patients.

Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study.

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.

Efficacy and Safety of Sodium Zirconium Cyclosilicate for Treatment of Hyperkalemia: An 11-Month Open-Label Extension of HARMONIZE.

Background: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for treatment of hyperkalemia. An open-label extension (OLE) of the -HARMONIZE study evaluated efficacy and safety of SZC for ≤11 months.

Methods: Patients from HARMONIZE with point-of-care device i-STAT K+ 3.

Randomized Controlled Trial of Subcutaneous Epoetin Alfa-epbx Versus Epoetin Alfa in End-Stage Kidney Disease.

Introduction: This double-blind, randomized controlled trial compared the safety and efficacy of subcutaneous epoetin alfa-epbx, an epoetin alfa biosimilar, with the reference product, epoetin alfa, in hemodialysis patients with end-stage kidney disease (ESKD) and anemia who were receiving epoetin alfa maintenance treatment.

Methods: Eligible patients ( = 320) were randomized (1:1) to subcutaneous epoetin alfa-epbx or epoetin alfa in a titration phase; patients who demonstrated stable subcutaneous dosing ( = 246) were re-randomized to receive subcutaneous epoetin alfa-epbx or epoetin alfa 1 to 3 times per week in a 16-week maintenance phase. Co-primary endpoints were least-squares mean difference between treatments in mean weekly hemoglobin concentration and mean weekly epoetin dose per kilogram body weight (BW) during the last 4 weeks of treatment in the maintenance phase.

Effect of bardoxolone methyl on the urine albumin-to-creatinine ratio in patients with type 2 diabetes and stage 4 chronic kidney disease.

Bardoxolone methyl attenuates inflammation by inducing nuclear factor erythroid-derived 2-related factor 2 and suppressing nuclear factor κB. The Bardoxolone Methyl Evaluation in Patients With Chronic Kidney Disease and Type 2 Diabetes (BEACON) trial was a phase 3 placebo-controlled, randomized, double-blind, parallel-group, international, multicenter trial in 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease. BEACON was terminated because of safety concerns, largely related to a significant increase in early heart failure events in patients randomized to bardoxolone methyl.

A Phase 3b, Randomized, Double-Blind, Placebo-Controlled Study of Sodium Zirconium Cyclosilicate for Reducing the Incidence of Predialysis Hyperkalemia.

Background: Patients with ESRD have minimal renal potassium excretion and, despite hemodialysis, often have persistent predialysis hyperkalemia. The DIALIZE study (NCT03303521) evaluated sodium zirconium cyclosilicate (SZC) in the management of hyperkalemia in hemodialysis patients.

Methods: In the DIALIZE study, a double-blind, placebo-controlled, phase 3b multicenter study, we randomized adults with ESRD who were managed by three-times weekly hemodialysis and had predialysis hyperkalemia to receive placebo or SZC 5 g once daily on non-dialysis days, and titrated towards maintaining normokalemia over 4 weeks, in 5 g increments to a maximum of 15 g.

Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia: A 12-Month Phase 3 Study.

Background And Objectives: Oral sodium zirconium cyclosilicate (formerly ZS-9) binds and removes potassium the gastrointestinal tract. Sodium zirconium cyclosilicate-associated restoration and maintenance of normokalemia and adverse events were evaluated in a two-part, open label, phase 3 trial.

Design, Setting, Participants, & Measurements: In the correction phase, adult outpatients with plasma potassium ≥5.

Economic and quality of life burden of anemia on patients with CKD on dialysis: a systematic review.

The overall cost and health-related quality of life (HRQoL) associated with current treatments for chronic kidney disease (CKD)-related anemia are not well characterized. A systematic literature review (SLR) was conducted on the costs and HRQoL associated with current treatments for CKD-related anemia among dialysis-dependent (DD) patients. The authors searched the Cochrane Library, MEDLINE, EMBASE, NHS EED, and NHS HTA for English-language publications.

Effects of bardoxolone methyl on body weight, waist circumference and glycemic control in obese patients with type 2 diabetes mellitus and stage 4 chronic kidney disease.

Aims: Obesity is associated with progression of chronic kidney disease (CKD). Treatment with bardoxolone methyl in a multinational phase 3 trial, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), resulted in increases in estimated glomerular filtration rate (eGFR) with concurrent reductions in body weight. We performed post-hoc analyses to further characterize reductions in body weight with bardoxolone methyl.

Effects of sucroferric oxyhydroxide and sevelamer carbonate on chronic kidney disease-mineral bone disorder parameters in dialysis patients.

Background: Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or sevelamer carbonate ('sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia.

Methods: After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.

Update on Anemia in ESRD and Earlier Stages of CKD: Core Curriculum 2018.

Anemia is a frequent complication during the later stages of chronic kidney disease. When present, it may cause symptoms such as fatigue and shortness of breath. The pathogenesis of anemia in chronic kidney disease is complex, but a central feature is a relative deficit of erythropoietin.