• The Journal of pathology · Jun 2007

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

    • M M van Timmeren, M C van den Heuvel, V Bailly, S J L Bakker, H van Goor, and C A Stegeman.
    • Department of Pathology and Laboratory Medicine, University Medical Centre Groningen and University of Groningen, The Netherlands. m.m.van.timmeren@path.umcg.nl
    • J. Pathol. 2007 Jun 1;212(2):209-17.

    AbstractKIM-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.Copyright 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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