Utility of Fractional Excretion of Urea in Acute Kidney Injury with Comparison to Fractional Excretion of Sodium: A Systematic Review and Meta-Analysis

Background Differentiating between intrinsic and prerenal acute kidney injury (AKI) presents a challenge. Here, we assessed the performance of the fractional excretion of urea (FEUrea) and compared it to the fractional excretion of sodium (FENa) in distinguishing intrinsic from prerenal AKI. Methods A thorough search was conducted in several databases until January 16, 2024. We included studies evaluating FEUrea, with or without FENa, for differentiating AKI etiologies in adults. We assessed the methodological quality using the QUADAS-2 and QUADAS-C tools. We performed a meta-analysis using the bivariate random effects model, with subgroup analyses to explore the impact of diuretic therapy on FEUrea, and direct statistical comparisons between FEUrea and FENa involving the subgroups with and without diuretics. Results We included 11 studies with 1108 hospitalized patients. Among eight studies (915 patients) evaluating FEUrea >35% for distinguishing intrinsic from prerenal AKI, the pooled sensitivity and specificity were 66% (95% CI, 49%–79%) and 75% (95% CI, 60%–85%), respectively. In a subset of six studies (302 patients) comparing FEUrea at 35% to FENa at 1% in patients not receiving diuretics, there were no significant differences in sensitivity (77% versus 89%, P=0.410) or specificity (80% versus 79%, P=0.956). In four studies, 244 patients on diuretics, FEUrea demonstrated lower sensitivity (52% versus 92%, P<0.001) but higher specificity (82% versus 44%, P<0.001) compared to FENa for the diagnosis of intrinsic AKI. Conclusions FEUrea has limited utility in differentiating intrinsic from prerenal AKI. FEUrea does not provide a superior alternative to FENa, even in patients receiving diuretics.