Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury.
BACKGROUND
Traditional blood and urine markers for the diagnosis of various renal diseases are insensitive and nonspecific. Kidney Injury Molecule-1 (KIM-1) is a type 1 transmembrane protein, with an immunoglobulin and mucin domain, whose expression is markedly up-regulated in the proximal tubule in the post-ischemic rat kidney. The ectodomain of KIM-1 is shed from cells. The current studies were carried out to evaluate whether KIM-1 is present in human acute renal failure and might serve as a urinary marker of acute renal tubular injury.


METHODS
Kidney tissue samples from six patients with biopsy-proven acute tubular necrosis (ATN) were evaluated by immunohistochemistry for expression of KIM-1. Urine samples were collected from an additional thirty-two patients with various acute and chronic renal diseases, as well as from eight normal controls. Urinary KIM-1 protein was detected by immunoassay and was quantified by ELISA.


RESULTS
There was extensive expression of KIM-1 in proximal tubule cells in biopsies from 6 of 6 patients with confirmed ATN. The normalized urinary KIM-1 levels were significantly higher in patients with ischemic ATN (2.92 +/- 0.61; N = 7) compared to levels in patients with other forms of acute renal failure (0.63 +/- 0.17, P < 0.01; N = 16) or chronic renal disease (0.72 +/- 0.37, P < 0.01; N = 9). Adjusted for age, gender, length of time delay between the initial insult and sampling of the urine, a one-unit increase in normalized KIM-1 was associated with a greater than 12-fold (OR 12.4, 95% CI 1.2 to 119) risk for the presence of ATN. Concentrations of other urinary biomarkers, including total protein, gamma-glutamyltransferase, and alkaline phosphatase, did not correlate with clinical diagnostic groupings.


CONCLUSIONS
A soluble form of human KIM-1 can be detected in the urine of patients with ATN and may serve as a useful biomarker for renal proximal tubule injury facilitating the early diagnosis of the disease and serving as a diagnostic discriminator.
Han
Won K
WK
Medical Services, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Bailly
Veronique
V
Abichandani
Rekha
R
Thadhani
Ravi
R
Bonventre
Joseph V
JV
D058186:Acute Kidney Injury / Q000175:diagnosis / Q000652:urine; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000652:urine*; D005260:Female; D006801:Humans; D007683:Kidney Tubular Necrosis, Acute / Q000652:urine; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; C110936:Havcr1 protein, rat