title: Tubular kidney injury molecule-1 (KIM-1) in human renal disease.
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 (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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University Medical Centre Groningen and University of Groningen, The Netherlands. m.m.van.timmeren@path.umcg.nl
authors.forename: M M
authors.initials: MM
authors.lastname: van Timmeren
authors.forename: M C
authors.initials: MC
authors.lastname: van den Heuvel
authors.forename: V
authors.initials: V
authors.lastname: Bailly
authors.forename: S J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: H
authors.initials: H
authors.lastname: van Goor
authors.forename: C A
authors.initials: CA
authors.lastname: Stegeman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate / Q000502:physiology; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000652:urine; D008875:Middle Aged; D011991:Receptors, Virus / Q000032:analysis*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus