Urinary N-Acetyl-β-(D)-Glucosaminidase Activity and Kidney Injury Molecule-1 Level Are Associated with Adverse Outcomes in Acute Renal Failure

Abstract

The role of urinary biomarkers of kidney injury in the prediction of adverse clinical outcomes in acute renal failure (ARF) has not been well described. The relationship between urinary N-acetyl-␤-(D)-glucosaminidase activity (NAG) and kidney injury molecule-1 (KIM-1) level and adverse clinical outcomes was evaluated prospectively in a cohort of 201 hospitalized patients with ARF. NAG was measured by spectrophotometry, and KIM-1 was measured by a microsphere-based Luminex technology. Mean Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score was 16, 43% had sepsis, 39% required dialysis, and hospital mortality was 24%. Urinary NAG and KIM-1 increased in tandem with APACHE II and Multiple Organ Failure scores. Compared with patients in the lowest quartile of NAG, the second, third, and fourth quartile groups had 3.0-fold (95% confidence interval [CI] 1.3 to 7.2), 3.7-fold (95% CI 1.6 to 8.8), and 9.1-fold (95% CI 3.7 to 22.7) higher odds, respectively, for dialysis requirement or hospital death (P < 0.001). This association persisted after adjustment for APACHE II, Multiple Organ Failure score, or the combined covariates cirrhosis, sepsis, oliguria, and mechanical ventilation. Compared with patients in the lowest quartile of KIM-1, the second, third, and fourth quartile groups had 1.4-fold (95% CI 0.6 to 3.0), 1.4-fold (95% CI 0.6 to 3.0), and 3.2-fold (95% CI 1.4 to 7.4) higher odds, respectively, for dialysis requirement or hospital death (P ‫؍‬ 0.034). NAG or KIM-1 in combination with the covariates cirrhosis, sepsis, oliguria, and mechanical ventilation yielded an area under the receiver operator characteristic curve of 0.78 (95% CI 0.71 to 0.84) in predicting the composite outcome. Urinary markers of kidney injury such as NAG and KIM-1 can predict adverse clinical outcomes in patients with ARF.

Comparison of Kidney Injury Molecule-1 and Other Nephrotoxicity Biomarkers in Urine and Kidney Following Acute Exposure to Gentamicin, Mercury, and Chromium

“…A sensitive high-throughput method has been developed to quantify urinary Kim-1 by a sandwich ELISA and now a Luminex-based bead assay (Liangos et al, 2007). Another methodological advantage of Kim-1 is that it is stable in urine and no stabilizing buffer needed for the collected urine samples prior to freezing and storage for later analysis.…”

Review article: Acute kidney injury in critical illness

“…30,31 Several small studies have found that a range on novel kidney injury-specific biomarkers, including urinary cystatin C, a1-microglobulin, N-acetylbeta-(D)-glucosaminidase, and retinol-binding protein correlate with severe AKI requiring RRT in hospitalized patients. 29,31,32 Overall, these candidate biomarkers are very promising; however, currently they are not widely available. It is probable that these biomarkers, either as a panel or coupled with clinical variables, will further enhance our capacity for early diagnosis and prognosis of AKI.…”

Urinary Biomarkers in the Early Detection of Acute Kidney Injury after Cardiac Surgery

“…These include N-acetyl-␤-D-glucosaminidase (NAG), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, and IL-18 (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). However, there are no previously reported data for the temporal expression pattern of urinary KIM-1 and NAG before the development of AKI in adult patients.…”