Tubular kidney injury molecule-1 (KIM-1) in human renal disease

J Pathol. 2007 Jun;212(2):209-17. doi: 10.1002/path.2175.


KIM-1, a transmembrane tubular protein with unknown function, is undetectable in normal kidneys, but is markedly induced in experimental renal injury. The KIM-1 ectodomain is cleaved, detectable in urine, and reflects renal damage. KIM-1 expression in human renal biopsies and its correlation with urinary KIM-1 (uKIM-1) is unknown. In biopsies from various renal diseases (n = 102) and controls (n = 7), the fraction of KIM-1 positive tubules and different renal damage parameters were scored. Double labelling was performed for KIM-1 with macrophages (MØ), alpha-smooth muscle actin (alpha-SMA), proximal (aquaporin-1) and distal (E-cadherin) tubular markers and a dedifferentiation marker (vimentin). uKIM-1 at the time of biopsy (n = 53) was measured by ELISA. Renal KIM-1 was significantly increased in all diseases versus controls (p < 0.05), except minimal change. KIM-1 was primarily expressed at the luminal side of dedifferentiated proximal tubules, in areas with fibrosis (alpha-SMA) and inflammation (MØ). Independent of the disease, renal KIM-1 correlated positively with renal damage, negatively with renal function, but not with proteinuria. uKIM-1 was increased in renal patients versus controls (p < 0.001), including minimal change, and correlated positively with tissue KIM-1 and MØ, negatively with renal function, but not with proteinuria. In conclusion, KIM-1 is upregulated in renal disease and is associated with renal fibrosis and inflammation. uKIM-1 is also associated with inflammation and renal function, and reflects tissue KIM-1, indicating that it can be used as a non-invasive biomarker in renal disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / analysis
  • Child
  • Child, Preschool
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Fibrosis
  • Glomerular Filtration Rate / physiology
  • Hepatitis A Virus Cellular Receptor 1
  • Humans
  • Immunohistochemistry / methods
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Kidney Diseases / physiopathology
  • Kidney Tubules / metabolism
  • Kidney Tubules / physiopathology
  • Male
  • Membrane Glycoproteins / analysis*
  • Membrane Glycoproteins / urine
  • Middle Aged
  • Receptors, Virus / analysis*
  • Up-Regulation / physiology


  • Biomarkers
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Membrane Glycoproteins
  • Receptors, Virus