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Abstract: PO0604

High Oxalate Concentrations Increase Risk for Sudden Cardiac Death in Dialysis Patients

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Pfau, Anja Christine, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Ermer, Theresa, Universitatsklinikum Erlangen, Erlangen, Bayern, Germany
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
  • Tio, Maria Clarissa, Brigham and Women's Hospital Department of Medicine, Boston, Massachusetts, United States
  • Genser, Bernd, Ruprecht Karls Universitat Heidelberg Mannheimer Institut fur Public Health, Mannheim, Baden-Württemberg, Germany
  • Reichel, Martin, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Finkelstein, Fredric O., Yale University Department of Internal Medicine, New Haven, Connecticut, United States
  • März, Winfried, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Wanner, Christoph, Julius-Maximilians-Universitat Wurzburg, Wurzburg, Bayern, Germany
  • Waikar, Sushrut S., Boston University School of Medicine, Boston, Massachusetts, United States
  • Eckardt, Kai-Uwe, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Aronson, Peter S., Yale University Department of Internal Medicine, New Haven, Connecticut, United States
  • Drechsler, Christiane, Julius-Maximilians-Universitat Wurzburg, Wurzburg, Bayern, Germany
  • Knauf, Felix, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
Background

The clinical significance of accumulating toxic terminal metabolites such as oxalate in kidney failure patients is imperfectly defined. Our study evaluated whether oxalate concentrations are associated with risk of all-cause mortality and cardiovascular events in a cohort of patients with kidney failure requiring chronic dialysis.

Methods

To relate all-cause death and cardiovascular events to serum oxalate, we performed a post-hoc analysis of a randomized controlled trial conducted between March 1998 and October 2002 that comprised 1255 European hemodialysis patients with diabetes who were followed up for a median of 4 years (4D Study).
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 with a mean (SD) age of 66.3 (8.3) years had baseline oxalate measurements with a median (IQR) oxalate concentration of 42.4 (30) micromolar. During follow-up, 548 patients died, including 139 (25.4%) patients who died from sudden cardiac death. A total of 413 patients reached the primary composite cardiovascular endpoint, which comprised cardiac death, nonfatal myocardial infarction, and fatal or nonfatal stroke. Participants in the highest oxalate quartile (above 59.7 micromolar) had a 40% increased risk for cardiovascular events (adjusted HR 1.40, 95% CI 1.08-1.81) and a 62% increased risk of sudden cardiac death (adjusted HR 1.62; 95% CI 1.03-2.56), compared to patients in the lowest quartile (below 29.6 micromolar). The associations remained when accounting for competing risks, and with oxalate as a continuous variable, and could be reproduced in a separate cohort of 104 US dialysis patients.

Conclusion

Elevated oxalate concentrations are 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.

Funding

  • Other NIH Support