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

M. M. van Timmeren*, Marius C. van den Heuvel, V. Bailly, S. J. L. Bakker, H. van Goor, C. A. Stegeman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

389 Citations (Scopus)

Abstract

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 (MO), a-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-I was primarily expressed at the luminal side of dedifferentiated proximal tubules, in areas with fibrosis (a-SMA) and inflammation (NIO). 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 MO, 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. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Original languageEnglish
Pages (from-to)209-217
Number of pages9
JournalThe Journal of Pathology
Volume212
Issue number2
DOIs
Publication statusPublished - Jun-2007

Keywords

  • kidney injury molecule-1
  • pathophysiology of renal disease and progression
  • renal biopsy
  • renal tubular epithelial cells
  • renal fibrosis
  • urinary biomarker
  • GLOMERULAR-FILTRATION-RATE
  • CELL-ADHESION
  • MEMBRANOUS NEPHROPATHY
  • URINARY-EXCRETION
  • PROTEINURIA
  • EXPRESSION
  • BIOMARKER
  • SELECTIVITY
  • MECHANISMS
  • CREATININE

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