High Oxalate Concentrations Correlate with Increased Risk for Sudden Cardiac Death in Dialysis Patients

• Published in: Journal of the American Society of Nephrology Vol. 32; no. 9; pp. 2375 - 2385
• Main Authors: Pfau, Anja, Ermer, Theresa, Coca, Steven G, Tio, Maria Clarissa, Genser, Bernd, Reichel, Martin, Finkelstein, Fredric O, März, Winfried, Wanner, Christoph, Waikar, Sushrut S, Eckardt, Kai-Uwe, Aronson, Peter S, Drechsler, Christiane, Knauf, Felix
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.09.2021
• Subjects: Aged; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Clinical Research; Death, Sudden, Cardiac - epidemiology; Female; Humans; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - mortality; Kidney Failure, Chronic - therapy; Male; Middle Aged; Oxalates - blood; Proportional Hazards Models; Renal Dialysis; Retrospective Studies; Risk Factors; cardiovascular disease; uremic toxins; sudden cardiac death; chronic kidney failure; oxalate; chronic hemodialysis
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2020121793

The clinical significance of accumulating toxic terminal metabolites such as oxalate in patients with kidney failure is not well understood. To evaluate serum oxalate concentrations and risk of all-cause mortality and cardiovascular events in a cohort of patients with kidney failure requiring chronic dialysis, we performed a analysis of the randomized German Diabetes Dialysis (4D) Study; this study included 1255 European patients on hemodialysis with diabetes followed-up for a median of 4 years. The results obtained Cox proportional hazards models were confirmed by competing risk regression and restricted cubic spline modeling in the 4D Study cohort and validated in a separate cohort of 104 US patients on dialysis after a median follow-up of 2.5 years. A total of 1108 patients had baseline oxalate measurements, with a median oxalate concentration of 42.4 µM. During follow-up, 548 patients died, including 139 (25.4%) from sudden cardiac death. A total of 413 patients reached the primary composite cardiovascular end point (cardiac death, nonfatal myocardial infarction, and fatal or nonfatal stroke). Patients in the highest oxalate quartile (≥59.7 µM) had a 40% increased risk for cardiovascular events (adjusted hazard ratio [aHR], 1.40; 95% confidence interval [95% CI], 1.08 to 1.81) and a 62% increased risk of sudden cardiac death (aHR, 1.62; 95% CI, 1.03 to 2.56), compared with those in the lowest quartile (≤29.6 µM). The associations remained when accounting for competing risks and with oxalate as a continuous variable. Elevated serum oxalate is a novel risk factor for cardiovascular events and sudden cardiac death in patients on dialysis. Further studies are warranted to test whether oxalate-lowering strategies improve cardiovascular mortality in patients on dialysis.