Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury.

By W. Han, V. Bailly, R. Abichandani, R. Thadhani, Joseph V. Bonventre. Kidney International, 2002

1,890 citations recorded by the source corpus.

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.

Subfields: Immunology, Molecular Biology, Nephrology

View Paper: https://www.semanticscholar.org/paper/7c8506298357b281422ab43c3c93a8fce45adc0e

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In Immunology

1. Arlene H. Sharpe
2. G. Dranoff
3. G. Freeman
4. P. Devarajan
5. V. Vaidya
6. Baogong Zhu
7. M. Butte
8. D. Umetsu

In Molecular Biology

1. P. Devarajan
2. J. Weinberg
3. V. Vaidya
4. M. Ferguson
5. G. Dranoff
6. Joseph V. Bonventre

In Nephrology

1. P. Devarajan
2. V. Vaidya
3. Joseph V. Bonventre
4. M. Ferguson

Citations in the corpus

• Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure. (2003, background): “Human KIM-1 protein is expressed by the proximal tubule of humans with ARF, and the ectodomain appears in the urine of patients with ARF (80).”
• Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. (2003, background): “Recent elegant studies have shown that KIM-1 can be detected in the kidney biopsy and urine of patients with ischemic acute tubular necrosis (45).”
• Recent advances in the pathophysiology of ischemic acute renal failure. (2003, background): “In addition, it is expressed on the proximal tubule epithelial cells in human kidney biopsy sections from patients with acute tubular necrosis (141).”
• Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. (2006, methodology): “Although we have previously developed a sensitive ELISA assay to measure human KIM-1 in the urine (12) this unfortunately does not detect either rat or mouse Kim-1.”
• Biomarkers of acute kidney injury. (2008, background): “We have found that the ectodomain of KIM-1 is shed from cells in vitro (53) and in vivo into the urine in rodents (54) and humans (55) after proximal tubular injury (Table 3).”
• Cardiorenal syndrome. (2008, positive): “Kidney injury molecule 1 is a protein detectable in the urine after ischemic or nephrotoxic insults to proximal tubular cells (49–51) and seems to be highly specific for ischemic AKI.”
• TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. (2007, background): “In addition, TIM-1 ectodomain has been shown to be shed from the injured kidney (Han et al., 2002) and may regulate the recognition of apoptotic cells either by opsonization or by blockade.”
• TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity (2010, background): “The soluble form is excreted in the urine and is a useful marker of kidney injury (64).”
• Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. (2004, neutral): “These include increased urinary excretion of kidney injury molecule-1 (12), IL-18 (13), and tubular enzymes (14).”
• Update on mechanisms of ischemic acute kidney injury. (2006, background): “cal membranes of proximal tubule epithelial cells, where it may play a role in renal regeneration (187,188).”