Urinary biomarkers in the early diagnosis of acute kidney injury

Abstract

A change in the serum creatinine is not sensitive for an early diagnosis of acute kidney injury. We evaluated urinary levels of matrix metalloproteinase-9 (MMP-9), N-acetyl-beta-D-glucosaminidase (NAG), and kidney injury molecule-1 (KIM-1) as biomarkers for the detection of acute kidney injury. Urine samples were collected from 44 patients with various acute and chronic kidney diseases, and from 30 normal subjects in a cross-sectional study. A case-control study of children undergoing cardio-pulmonary bypass surgery included urine specimens from each of 20 patients without and with acute kidney injury. Injury was defined as a greater than 50% increase in the serum creatinine within the first 48 h after surgery. The biomarkers were normalized to the urinary creatinine concentration at 12, 24, and 36 h after surgery with the areas under the receiver-operating characteristic curve compared for performance. In the cross-sectional study, the area under the curve for MMP-9 was least sensitive followed by KIM-1 and NAG. Combining all three biomarkers achieved a perfect score diagnosing acute kidney injury. In the case-control study, KIM-1 was better than NAG at all time points, but combining both was no better than KIM-1 alone. Urinary MMP-9 was not a sensitive marker in the case-control study. Our results suggest that urinary biomarkers allow diagnosis of acute kidney injury earlier than a rise in serum creatinine.

Figure 1. Comparison of various urinary biomarkers in cross-sectional study

Combined box and whisker and dot plot of normalized urinary MMP-9, NAG, and KIM-1 levels is shown among control (non-AKI), AKI, and UTI groups. AKI, acute kidney injury; UTI, urinary tract infection.

Figure 2. ROC analysis for normalized urinary biomarkers in cross-sectional study

ROC curves of normalized MMP-9, NAG, and KIM-1 as a single test and in combination were plotted. The greater the displacement above and to the left of the line identified, the greater the likelihood that raised values of the test will identify AKI.

Figure 3. Pattern of urinary biomarker expression in case–control study

Graphs showing mean normalized urine KIM-1, NAG, and MMP-9 concentrations at multiple time points after cardiopulmonary bypass. Error bars are s.e.