Background The clinical significance of accumulating toxic terminal metabolites such as oxalate in kidney failure patients is not well understood.
Methods To evaluate serum oxalate concentrations and risk of all-cause mortality and cardiovascular events in a cohort of kidney failure patients requiring chronic dialysis, we performed a post-hoc analysis of the randomized German Diabetes Dialysis Study (4D Study); this study included 1255 European hemodialysis patients with diabetes followed up for a median of 4 years. The results obtained via Cox proportional hazards models were confirmed by competing risk regression and restricted cubic spline modeling in the 4D cohort and validated in a separate cohort of 104 US dialysis patients after a median follow-up of 2.5 years.
Results A total of 1108 patients had baseline oxalate measurements, with a median oxalate concentration of 42.4 µM. During follow-up, 548 died, including 139 (25.4%) from sudden cardiac death. A total of 413 patients reached the primary composite cardiovascular endpoint (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.
Conclusions Elevated serum oxalate is a novel risk factor for cardiovascular events and sudden cardiac death in dialysis patients. Further studies are warranted to test whether oxalate-lowering strategies improve cardiovascular mortality in dialysis patients.
Introduction: Alterations in oxalate homeostasis are associated with kidney stone disease and progression of chronic kidney disease (CKD). However, accurate measurement of plasma oxalate (P Ox) concentrations in large patient cohorts is challenging as prompt acidification of samples has been deemed necessary. In the present study, we investigated the effects of variations in sample handling on P Ox results and examined an alternative strategy to the established preanalytical procedures. Methods: The effect of storage time at room temperature (RT) and maintenance of samples at À80 C was tested. P Ox was measured in 1826 patients enrolled in the German Chronic Kidney Disease (GCKD) study, an ongoing multicenter, prospective, observational cohort study. Results: We demonstrate that P Ox concentrations increased rapidly when samples were maintained at RT. This was most relevant for P Ox <10 mM, as concentrations more than doubled within a few hours. Immediate freezing on dry ice and storage at À80 C provided stable results and allowed postponement of acidification for >1 year. In the patients of the lowest estimated glomerular filtration rate (eGFR) quartile, median P Ox was 2.7 mM (interquartile range [IQR] <2.0-4.2) with a median eGFR of 25.1 ml/min per 1.73 m 2 (IQR 20.3-28.1). Conclusion: We conclude that immediate freezing and maintenance of plasma samples at-80 C facilitates the sample collection process and allows accurate P Ox assessment in large cohorts. The present study may serve as a reference for sample handling to assess P Ox in clinical trials and to determine its role in CKD progression.
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