Elevated serum urea levels in patients with nondialysis-dependent chronic kidney disease (CKD) predict cardiovascular events and death, according to study findings presented at the European Renal Association (ERA) 59th Congress held in Paris, France, and virtually.

Ziad Massy, MD, PhD, of Ambroise Paré University Hospital, Boulogne-Billancourt, France, and colleagues stratified 2507 patients from the CKD-REIN cohort by baseline serum urea level. Over a median of 3 years, 451 patients experienced their first atheromatous or nonatheromatous cardiovascular event. The overall incidence rate was 7.1 per 100 person-years.

In adjusted analyses, patients with serum urea levels in the top tertile (15.1 mmol/L or higher) had a significant 2.1-fold increased risk for cardiovascular events compared with those who had levels in the bottom tertile (less than 10.5 mmol/L), the investigators reported. The middle tertile of serum urea (10.5–15.1 mmol/L) was associated with a nonsignificant 1.3-fold increased risk of cardiovascular events. The cardiovascular events rate was 4.1, 6.3, and 11.6 per 100 person-years for the bottom, middle, and top tertile, respectively. Of the full cohort, 54% had a history of cardiovascular disease.

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Over a median 4.8 years, 407 patients died before initiating kidney replacement therapy at a rate of 4.0 per 100 person-years. Compared with the bottom tertile of serum urea, the risk for all-cause mortality was a nonsignificant 1.3-fold higher for the middle tertile and a significant 1.7-fold higher for the top tertile, the investigators reported.

“Beyond [cardiovascular] risk factors including eGFR, this hypothesis-generating study suggests that serum urea level is a predictor of cardiovascular outcomes in patients with moderate to advanced CKD,” Dr Massy’s team concluded in a study abstract. Further research is needed to confirm the findings and explore mechanisms, including whether urea is a direct or indirect uremic toxin, as some studies indicate.


Laville S, Couturier A, Lambert O, et al. Serum urea levels and cardiovascular disease in patients with chronic kidney disease. Presented at: ERA 59th Congress; May 19-22, 2022, Paris, France, and virtual. Abstract MO496.