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 alpha(1)- and beta(2)-microglobulin, cystatin C, retinol-binding protein, alpha-glutathione S-transferase, gamma-glutamyltransferase, lactate dehydrogenase, and N-acetyl-beta-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 alpha(1)-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 alpha(1)-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 alpha(1)-microglobulin >20 g/mol of creatinine. CONCLUSION: In nonoliguric ATN, increased urinary excretion of cystatin C and alpha(1)-microglobulin may predict an unfavorable outcome, as reflected by the requirement for RRT.