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

Fishbane, Steven; Charytan, David M; Chertow, Glenn M; Ford, Martin; Kovesdy, Csaba P; Pergola, Pablo E; Pollock, Carol; Spinowitz, Bruce
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. This consensus guideline aims to provide recommendations in relation to clinical practice. Available published evidence was evaluated through a systematic literature review, and the nominal group technique was used to develop consensus recommendations from a panel of experienced nephrologists, covering monitoring, dietary restrictions, prescription of K+ binders, and concomitant prescription of renin-angiotensin-aldosterone system inhibitors. Recent studies have shown that K+ binders reduce the incidence of hyperkalemia, but further evidence is needed in areas including whether reduced-K+ diets or treatment with K+ binders improve patient-centered outcomes. Treatment of hyperkalemia in the hemodialysis setting is complex, and decisions need to be tailored for individual patients.
PMID: 34364782
ISSN: 1532-8503
CID: 5006052

Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia

Guedes, Murilo; Muenz, Daniel G; Zee, Jarcy; Bieber, Brian; Stengel, Benedicte; Massy, Ziad A; Mansecal, Nicolas; Wong, Michelle M Y; Charytan, David M; Reichel, Helmut; Waechter, Sandra; Pisoni, Ronald L; Robinson, Bruce M; Pecoits-Filho, Roberto
BACKGROUND:Approximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks. METHODS:The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations. RESULTS:Compared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml. CONCLUSIONS:Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.
PMID: 34244326
ISSN: 1533-3450
CID: 4932212

The Effects of Canagliflozin on Heart Failure and Cardiovascular Death by Baseline Participant Characteristics: Analysis of the CREDENCE Trial

Arnott, Clare; Li, Jing-Wei; Cannon, Christopher P; de Zeeuw, Dick; Neuen, Brendon L; Heerspink, Hiddo J L; Charytan, David M; Agarwal, Anubha; Huffman, Mark D; Figtree, Gemma A; Bakris, George; Chang, Tara I-Hsin; Feng, Kent; Rosenthal, Norman; Zinman, Bernard; Jardine, Meg J; Perkovic, Vlado; Neal, Bruce; Mahaffey, Kenneth W
Heart failure is prevalent in those with type 2 diabetes and chronic kidney disease and is associated with significant mortality and morbidity. In the CREDENCE trial canagliflozin reduced the risk of hospitalization for heart failure (HHF) or cardiovascular (CV) death by 31%. In this current analysis we sought to determine whether the effect of canagliflozin on HHF/CV death differed in subgroups defined by key baseline participant characteristics. Cox regression models were used to estimate hazard ratios and 95% confidence intervals. Canagliflozin was associated with a reduction in the relative risk of HHF/CV death regardless of age, sex, history of HF or CV disease, and the use of loop diuretics or GLP1 receptor agonists (all pinteraction >0.114). The absolute benefit of canagliflozin was greater in those at highest baseline risk, such as those with CV disease (50 fewer events/1000 patients treated over 2.5years versus 20 fewer events in those without CV disease) or advanced kidney disease (eGFR 30-45 ml/min/1.73m2 : 61 events prevented/1000 patients treated over 2.5 years versus 23 events in eGFR 60-90 ml/min/1.73m2 ). Canagliflozin consistently reduces the proportional risk of HHF/CV death across a broad range of subgroups with greater absolute benefits in those at highest baseline risk. This article is protected by copyright. All rights reserved.
PMID: 33769679
ISSN: 1463-1326
CID: 4823672

Outcomes among Hospitalized Chronic Kidney Disease Patients with COVID-19

Khatri, Minesh; Charytan, David M; Parnia, Sam; Petrilli, Christopher M; Michael, Jeffrey; Liu, David; Tatapudi, Vasishta; Jones, Simon; Benstein, Judith; Horwitz, Leora I
ISSN: 2641-7650
CID: 4966642

Mineralocorticoid Receptor Antagonists and Cardiovascular Health with Kidney Failure [Editorial]

Soomro, Qandeel H; Charytan, David M
PMID: 34117077
ISSN: 1555-905x
CID: 4900872

All-Cause Mortality and Progression to End-Stage Kidney Disease Following Percutaneous Revascularization or Surgical Coronary Revascularization in Patients with CKD

Charytan, David M; Zelevinsky, Katya; Wolf, Robert; Normand, Sharon-Lise T
Introduction/UNASSIGNED:Relative impacts of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) on mortality and end-stage kidney disease (ESKD) in chronic kidney disease (CKD) are uncertain. Methods/UNASSIGNED:Data from Massachusetts residents with CKD undergoing CABG or PCI from 2003 to 2012 were linked to the United States Renal Data System. Associations with death, ESKD, and combined death and ESKD were analyzed in propensity score-matched multivariable survival models. Results/UNASSIGNED:We identified 6805 CABG and 17,494 PCI patients. Among 3775 matched-pairs, multi-vessel disease was present in 97%, and stage 4 CKD was present in 11.9% of CABG and 12.2% of PCI patients. One-year mortality (CABG 7.7%, PCI 11.0%) was more frequent than ESKD (CABG 1.4%, PCI 1.7%). Overall survival was improved and ESKD risk decreased with CABG compared to PCI, but effects differed in the presence of left main disease and prior myocardial infarction (MI). Survival was worse following PCI than following CABG among patients with left main disease and without MI (hazard ratio = 3.7, 95% confidence interval = 1.3-10.5). ESKD risk was higher with PCI for individuals with left main disease and prior infarction (hazard ratio = 8.1, 95% confidence interval = 1.7-39.2). Conclusion/UNASSIGNED:Risks following CABG and PCI were modified by left main disease and prior MI. In individuals with CKD, survival was greater after CABG than after PCI in patients with left main disease but without MI, whereas ESKD risk was lower with CABG in those with left main and MI. Absolute risks of ESKD were markedly lower than for mortality, suggesting prioritizing mortality over ESKD in clinical decision making.
PMID: 34169198
ISSN: 2468-0249
CID: 4936922

Canagliflozin Reduces Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial

Heerspink, Hiddo J L; Oshima, Megumi; Zhang, Hong; Li, Jingwei; Agarwal, Rajiv; Capuano, George; Charytan, David M; Craig, Jagriti; de Zeeuw, Dick; Di Tanna, Gian Luca; Levin, Adeera; Neal, Bruce; Perkovic, Vlado; Wheeler, David C; Yavin, Yshai; Jardine, Meg J
RATIONALE AND OBJECTIVE/OBJECTIVE:Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs). STUDY DESIGN/METHODS:A randomized, double-blind, placebo-controlled, multicenter, international trial. SETTING AND PARTICIPANTS/METHODS:4,401 trial participants with T2DM, CKD, and urinary albumin:creatinine ratio >300-5000mg/g. INTERVENTIONS/METHODS:Participants were randomly assigned to receive canagliflozin 100mg/day or placebo. OUTCOMES/RESULTS:). RESULTS:, respectively; P-interaction=0.3), with similar results for AKI (P-interaction=0.9). Full recovery of kidney function within 30 days after an AKI event occurred more frequently with canagliflozin versus placebo (53.1% vs 35.4%; odds ratio: 2.2 [95% CI: 1.0, 4.7]; P=0.04). LIMITATIONS/CONCLUSIONS:Kidney-related AEs including AKI were investigator-reported and collected without central adjudication. Biomarkers of AKI and structural tubular damage were not measured and creatinine data after an AKI event were not available for all participants. CONCLUSION/CONCLUSIONS:Canagliflozin compared to placebo was associated with a reduced incidence of serious and non-serious kidney-related AEs in patients with T2DM and CKD. These results highlight the safety of canagliflozin with regard to adverse kidney disease events.
PMID: 34029680
ISSN: 1523-6838
CID: 4902992

Prasugrel and Ticagrelor in Patients with Drug-Eluting Stents and Kidney Failure

Mavrakanas, Thomas A; Kamal, Omer; Charytan, David M
BACKGROUND AND OBJECTIVES/OBJECTIVE:Prasugrel and ticagrelor have superior efficacy compared with clopidogrel in moderate CKD but have not been studied in kidney failure. The study objective is to determine the effectiveness and safety of prasugrel and ticagrelor in kidney failure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:This retrospective cohort study used United States Renal Data System data from 2012 to 2015. We identified all patients on dialysis who received a drug-eluting stent and were alive at 90 days after stent implantation. Inverse probability-weighted Cox proportional hazard models were used. Weights were estimated with propensity scores for multiple treatments. RESULTS:=0.98). A numerically higher incidence of clinically relevant bleeding was seen with prasugrel or ticagrelor compared with clopidogrel (weighted hazard ratio, 1.15; 95% confidence interval, 0.95 to 1.38 and weighted hazard ratio, 1.13; 95% confidence interval, 0.91 to 1.40, respectively). CONCLUSIONS:Prasugrel or ticagrelor does not seem to be associated with significant benefits compared with clopidogrel in patients with kidney failure treated with drug-eluting stents. PODCAST/UNASSIGNED:This article contains a podcast at
PMID: 33811128
ISSN: 1555-905x
CID: 4888652

Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial

Ye, Nan; Jardine, Meg J; Oshima, Megumi; Hockham, Carinna; Heerspink, Hiddo J L; Agarwal, Rajiv; Bakris, George; Schutte, Aletta E; Arnott, Clare; Chang, Tara I; Górriz, Jose L; Cannon, Christopher P; Charytan, David M; de Zeeuw, Dick; Levin, Adeera; Mahaffey, Kenneth W; Neal, Bruce; Pollock, Carol; Wheeler, David C; Luca Di Tanna, Gian; Cheng, Hong; Perkovic, Vlado; Neuen, Brendon L
BACKGROUND:People with type 2 diabetes and chronic kidney disease experience a high burden of hypertension, but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population are uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP-lowering therapy is also unknown. METHODS:The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) randomized people with type 2 diabetes and chronic kidney disease to canagliflozin or placebo. In a post hoc analysis, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP-lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mm Hg while receiving ≥3 classes of BP-lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups. RESULTS:interaction ≥0.35), as were effects on other key kidney, cardiovascular, and safety outcomes. CONCLUSIONS:In people with type 2 diabetes and chronic kidney disease, canagliflozin lowers systolic BP across all BP-defined subgroups and reduces the need for additional BP-lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP-lowering therapy in people with chronic kidney disease. Registration: URL:; Unique identifier: NCT02065791.
PMID: 33554616
ISSN: 1524-4539
CID: 4873652

Cost-Effectiveness of Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention in Patients With Chronic Kidney Disease and Acute Coronary Syndromes in the US Medicare Program

Reynolds, Matthew R; Gong, Tingting; Li, Shuling; Herzog, Charles A; Charytan, David M
Background Coronary revascularization provides important long-term clinical benefits to patients with high-risk presentations of coronary artery disease, including those with chronic kidney disease. The cost-effectiveness of coronary interventions in this setting is not known. Methods and Results We developed a Markov cohort simulation model to assess the cost-effectiveness of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with chronic kidney disease who were hospitalized with acute myocardial infarction or unstable angina. Model inputs were primarily drawn from a sample of 14 300 patients identified using the Medicare 20% sample. Survival, quality-adjusted life-years, costs, and cost-effectiveness were projected over a 20-year time horizon. Multivariable models indicated higher 30-day mortality and end-stage renal disease with both PCI and CABG, and higher stroke with CABG, relative to medical therapy. However, the model projected long-term gains of 0.72 quality-adjusted life-years (0.97 life-years) for PCI compared with medical therapy, and 0.93 quality-adjusted life-years (1.32 life-years) for CABG compared with PCI. Incorporation of long-term costs resulted in incremental cost-effectiveness ratios of $65 326 per quality-adjusted life-year gained for PCI versus medical therapy, and $101 565 for CABG versus PCI. Results were robust to changes in input parameters but strongly influenced by the background costs of the population, and the time horizon. Conclusions For patients with chronic kidney disease and high-risk coronary artery disease presentations, PCI and CABG were both associated with markedly increased costs as well as gains in quality-adjusted life expectancy, with incremental cost-effectiveness ratios indicating intermediate value in health economic terms.
PMID: 33787323
ISSN: 2047-9980
CID: 4858412