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Tubular kidney injury molecule‐1 (KIM‐1) in human renal disease
Author(s) -
van Timmeren MM,
van den Heuvel MC,
Bailly V,
Bakker SJL,
van Goor H,
Stegeman CA
Publication year - 2007
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2175
Subject(s) - renal function , kidney , inflammation , fibrosis , pathology , medicine , urinary system , proteinuria , renal biopsy , endocrinology
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 (M Ø ), α‐smooth muscle actin (α‐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 (α‐SMA) and inflammation (M Ø ). 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 M Ø , 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.