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Clinical Chemistry 0: 200302776, 2004; 10.1373/clinchem.2003.027763
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Received on September 25, 2003
Accepted on December 3, 2003

Proteomics and Protein Markers

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

Stefan Herget-Rosenthal 1*, Dennis Poppen 1, Johannes Hüsing 2, Günter Marggraf 3, Frank Pietruck 1, Heinz-Günther Jakob 3, Thomas Philipp 1, Andreas Kribben 1

1 Department of Nephrology, University Hospital, Essen, Germany
2 Institute for Medical Informatics, Biometry and Epidemiology, Medical School, University of Essen, Essen, Germany
3 Department of Thoracic and Cardiovascular Surgery, University Hospital, Essen, Germany

* To whom correspondence should be addressed. E-mail: stefan.herget-rosenthal{at}uni-essen.de.

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.


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