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 post-hoc 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 via 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.

草酸盐等毒性终末代谢物在肾衰竭患者体内蓄积的临床意义尚不清楚。

为了评估一组需要长期透析的肾衰竭患者的血清草酸盐浓度和全因死亡率和心血管事件的风险，我们对随机德国糖尿病透析 (4D) 研究进行了事后分析；这项研究包括 1255 名接受血液透析的糖尿病患者，随访时间中位数为 4 年。通过Cox 比例风险模型获得的结果在 4D 研究队列中通过竞争风险回归和受限三次样条建模得到证实，并在中位随访 2.5 年后在 104 名美国透析患者的单独队列中得到验证。

共有 1108 名患者进行了基线草酸盐测量，中位草酸盐浓度为 42.4 µM。随访期间，548 例患者死亡，其中 139 例 (25.4%) 死于心源性猝死。共有 413 名患者达到了主要复合心血管终点（心源性死亡、非致死性心肌梗死和致死性或非致死性卒中）。最高草酸盐四分位数 (≥59.7 µM) 的患者心血管事件风险增加 40%（调整后风险比 [aHR]，1.40；95% 置信区间 [95% CI]，1.08 至 1.81），风险增加 62%心源性猝死（aHR，1.62；95% CI，1.03 至 2.56）与最低四分位数 (≤29.6 µM) 相比。当考虑竞争风险并将草酸盐作为连续变量时，这些关联仍然存在。

升高的血清草酸盐是透析患者心血管事件和心源性猝死的新危险因素。需要进一步的研究来测试降低草酸盐的策略是否会改善透析患者的心血管死亡率。