Urea‐to‐Creatinine‐Ratio and the risk of 28‐day mortality in critically ill adults with or without Acute Kidney Injury: A post‐hoc analysis of a randomized clinical trial

BACKGROUND: The prognostic value of the urea-to-creatinine ratio in critically ill adults may vary according to the timing of measurement and baseline acute kidney injury status. We hypothesized that higher urea-to-creatinine ratios measured on study Days 1 and 7 would be associated with higher 28-day mortality, and that these associations would differ according to baseline acute kidney injury status. METHODS: We performed a post hoc analysis of the multicenter cluster-randomized trial. The urea-to-creatinine ratio was measured on study Days 1 and 7 (mmol/mmol). Restricted cubic spline-adjusted Cox models assessed associations between the urea-to-creatinine ratio and time to death through Day 28 in the overall population and according to baseline acute kidney injury status. Multivariable linear regression identified factors associated with Day 7 urea-to-creatinine ratio. RESULTS: The Day 1 and Day 7 analyses included 2613 and 2516 patients, respectively. The urea-to-creatinine ratio was higher on Day 7 than on Day 1 and lower in patients with baseline acute kidney injury than in those without baseline acute kidney injury. No clear association was observed between the Day 1 urea-to-creatinine ratio and 28-day mortality in the overall population or after stratification by baseline acute kidney injury status. The Day 7 urea-to-creatinine ratio was associated with 28-day mortality in the overall population and showed a U-shaped association in patients without baseline acute kidney injury, whereas no clear association was observed in patients with baseline acute kidney injury. In the Day 7 cohort without baseline acute kidney injury, low and high urea-to-creatinine ratio cohorts had higher mortality than the middle urea-to-creatinine ratio cohort, with adjusted hazard ratios of 2.06 (95% confidence interval, 1.30-3.26) and 2.21 (95% confidence interval, 1.45-3.38), respectively. Higher protein delivery and older age were associated with higher Day 7 urea-to-creatinine ratio, whereas baseline acute kidney injury, male sex, and higher body mass index were associated with lower Day 7 urea-to-creatinine ratio. CONCLUSION: No clear association between the Day 1 urea-to-creatinine ratio and 28-day mortality was observed in the overall population or after stratification by baseline acute kidney injury status. On Day 7, the urea-to-creatinine ratio was associated with 28-day mortality, with a U-shaped association in patients without baseline acute kidney injury but no clear association in patients with baseline acute kidney injury. The urea-to-creatinine ratio should be interpreted cautiously in patients with acute kidney injury.