Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies

Nat Biotechnol. 2010 May;28(5):478-85. doi: 10.1038/nbt.1623.


Kidney toxicity accounts both for the failure of many drug candidates as well as considerable patient morbidity. Whereas histopathology remains the gold standard for nephrotoxicity in animal systems, serum creatinine (SCr) and blood urea nitrogen (BUN) are the primary options for monitoring kidney dysfunction in humans. The transmembrane tubular protein kidney injury molecule-1 (Kim-1) was previously reported to be markedly induced in response to renal injury. Owing to the poor sensitivity and specificity of SCr and BUN, we used rat toxicology studies to compare the diagnostic performance of urinary Kim-1 to BUN, SCr and urinary N-acetyl-beta-D-glucosaminidase (NAG) as predictors of kidney tubular damage scored by histopathology. Kim-1 outperforms SCr, BUN and urinary NAG in multiple rat models of kidney injury. Urinary Kim-1 measurements may facilitate sensitive, specific and accurate prediction of human nephrotoxicity in preclinical drug screens. This should enable early identification and elimination of compounds that are potentially nephrotoxic.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / urine
  • Animals
  • Biomarkers, Pharmacological / metabolism
  • Biomarkers, Pharmacological / urine*
  • Blood Urea Nitrogen
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules / urine*
  • Cisplatin / toxicity
  • Creatinine / blood
  • Cyclosporine / toxicity
  • Drug Evaluation, Preclinical
  • Drug-Related Side Effects and Adverse Reactions
  • Gentamicins / toxicity
  • Histocytochemistry
  • Kidney Function Tests / methods*
  • Kidney Function Tests / standards
  • Kidney* / drug effects
  • Kidney* / injuries
  • Male
  • Oligonucleotide Array Sequence Analysis
  • ROC Curve
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Reperfusion Injury
  • Thioacetamide / toxicity


  • Biomarkers, Pharmacological
  • Cell Adhesion Molecules
  • Gentamicins
  • Havcr1protein, rat
  • Thioacetamide
  • Cyclosporine
  • Creatinine
  • Acetylglucosaminidase
  • Cisplatin