Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function

• Published in: Kidney international Vol. 79; no. 10; pp. 1119 - 1130
• Main Authors: Endre, Zoltán H., Pickering, John W., Walker, Robert J., Devarajan, Prasad, Edelstein, Charles L., Bonventre, Joseph V., Frampton, Christopher M., Bennett, Michael R., Ma, Qing, Sabbisetti, Venkata S., Vaidya, Vishal S., Walcher, Angela M., Shaw, Geoffrey M., Henderson, Seton J., Nejat, Maryam, Schollum, John B.W., George, Peter M.
• Format: Journal Article
• Language: English
• Published: Basingstoke Elsevier Inc 01.05.2011; Nature Publishing Group; Elsevier Limited
• Subjects: acute kidney injury; Acute Kidney Injury - diagnosis; Acute Kidney Injury - physiopathology; Acute Kidney Injury - urine; Acute-Phase Proteins - urine; Adult; Aged; Area Under Curve; Biological and medical sciences; Biomarkers - urine; clinical trail; Critical Illness; diagnosis; Female; gamma-Glutamyltransferase - urine; Glomerular Filtration Rate; Humans; Interleukin-18 - urine; Kidneys; Lipocalin-2; Lipocalins - urine; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Proto-Oncogene Proteins - urine; Renal Dialysis; Time Factors; Urinary system involvement in other diseases. Miscellaneous; clinical trail; diagnosis; acute kidney injury; glomerular filtration rate; Kidney disease; Performance evaluation; Human; Urine; Nephrology; Urinary system disease; Renal function; Critically ill; Acute kidney injury; Biological marker; Biological indicator; Duration; Urology; Glomerular filtration rate; Diagnosis
• ISSN: 0085-2538; 1523-1755; 1523-1755
• DOI: 10.1038/ki.2010.555

To better understand the diagnostic and predictive performance of urinary biomarkers of kidney injury, we evaluated γ-glutamyltranspeptidase (GGT), alkaline phosphatase (AP), neutrophil-gelatinase-associated lipocalin (NGAL), cystatin C (CysC), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in a prospective observational study of 529 patients in 2 general intensive care units (ICUs). Comparisons were made using the area under the receiver operator characteristic curve (AUC) for diagnosis or prediction of acute kidney injury (AKI), dialysis, or death, and reassessed after patient stratification by baseline renal function (estimated glomerular filtration rate, eGFR) and time after renal insult. On ICU entry, no biomarker had an AUC above 0.7 in the diagnosis or prediction of AKI. Several biomarkers (NGAL, CysC, and IL-18) predicted dialysis (AUC over 0.7), and all except KIM-1 predicted death at 7 days (AUC between 0.61 and 0.69). Performance was improved by stratification for eGFR or time or both. With eGFR <60ml/min, CysC and KIM-1 had AUCs of 0.69 and 0.73, respectively, within 6h of injury, and between 12 and 36h, CysC (0.88), NGAL (0.85), and IL-18 (0.94) had utility. With eGFR >60ml/min, GGT (0.73), CysC (0.68), and NGAL (0.68) had the highest AUCs within 6h of injury, and between 6 and 12h, all AUCs except AP were between 0.68 and 0.78. Beyond 12h, NGAL (0.71) and KIM-1 (0.66) performed best. Thus, the duration of injury and baseline renal function should be considered in evaluating biomarker performance to diagnose AKI.