Urinary biomarkers in the early diagnosis of acute kidney injury.
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.
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. won.han@jefferson.edu
W K
WK
Han
S S
SS
Waikar
A
A
Johnson
R A
RA
Betensky
C L
CL
Dent
P
P
Devarajan
J V
JV
Bonventre
D000118:Acetylglucosaminidase / Q000652:urine*; D058186:Acute Kidney Injury / Q000652:urine*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D042241:Early Diagnosis; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000652:urine*; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D011446:Prospective Studies; D011991:Receptors, Virus
D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D000118:Acetylglucosaminidase; D020780:Matrix Metalloproteinase 9