Prognostic Value of Tubular Proteinuria and Enzymuria in Nonoliguric Acute Tubular Necrosis

Background: Acute tubular necrosis (ATN) has high mortality, especially in patients who require renal replacement therapy (RRT). We prospectively studied the diagnostic accuracy of the urinary excretion of low-molecular-weight proteins and enzymes as predictors of a need for RRT in ATN. Methods: In 73 consecutive patients with initially nonoliguric ATN, we measured urinary excretion of α1- and β2-microglobulin, cystatin C, retinol-binding protein, α-glutathione S -transferase, γ-glutamyltransferase, lactate dehydrogenase, and N -acetyl-β-d-glucosaminidase early in the course of ATN. Results: Twenty-six patients (36%) required RRT a median of 4 (interquartile range, 2–6) days after detection of proteinuria and enzymuria. Patients who required RRT had higher urinary cystatin C and α1-microglobulin [median (interquartile range), 1.7 (1.2–4.1) and 34.5 (26.6–45.1) g/mol of creatinine] than patients who did not require RRT [0.1 (0.02–0.5) and 8.0 (5.0–17.5) g/mol of creatinine]. Urinary excretion of cystatin C and α1-microglobulin had the highest diagnostic accuracies in identifying patients requiring RRT as indicated by the largest areas under the ROC curves: 0.92 (95% confidence interval, 0.86–0.96) and 0.86 (0.78–0.92), respectively. Sensitivity and specificity were 92% (95% confidence interval, 83–96%) and 83% (73–90%), respectively, for urinary cystatin C >1 g/mol of creatinine, and 88% (78–93%) and 81% (70–88%) for urinary α1-microglobulin >20 g/mol of creatinine. Conclusion: In nonoliguric ATN, increased urinary excretion of cystatin C and α1-microglobulin may predict an unfavorable outcome, as reflected by the requirement for RRT.