title: Kidney injury molecule-1 expression in transplant biopsies is a sensitive measure of cell injury.
abstract: Kidney injury molecule-1 (KIM-1) is a specific histological biomarker for diagnosing early tubular injury on renal biopsies. In this study, KIM-1 expression was quantitated in renal transplant biopsies by immunohistochemistry and correlated with renal function. None of the 25 protocol biopsies showed detectable tubular injury on histologic examination, yet 28% had focal positive KIM-1 expression. Proximal tubule KIM-1 expression was present in all biopsies from patients with histological changes showing acute tubular damage and deterioration of kidney function. In this group, higher KIM-1 staining predicted a better outcome with improved blood urea nitrogen (BUN), serum creatinine, and estimated glomerular filtration rate (eGFR) over an ensuing 18 months. KIM-1 was expressed focally in affected tubules in 92% of kidney biopsies from patients with acute cellular rejection. By contrast, there was little positive staining for Ki-67, a cell proliferation marker, in any of the groups. KIM-1 expression significantly correlated with serum creatinine and BUN, and inversely with the eGFR on the biopsy day. Our study shows that KIM-1 staining sensitively and specifically identified proximal tubular injury and correlated with the degree of renal dysfunction. KIM-1 expression is more sensitive than histology for detecting early tubular injury, and its level of expression in transplant biopsies may indicate the potential for recovery of kidney function.
authors.affiliation: Division of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: Zhang
authors.forename: L I
authors.initials: LI
authors.lastname: Rothblum
authors.forename: W K
authors.initials: WK
authors.lastname: Han
authors.forename: T M
authors.initials: TM
authors.lastname: Blasick
authors.forename: S
authors.initials: S
authors.lastname: Potdar
authors.forename: J V
authors.initials: JV
authors.lastname: Bonventre
mesh_terms: D000208:Acute Disease; D000328:Adult; D000818:Animals; D001706:Biopsy; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000473:pathology; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis* / Q000473:pathology; D016030:Kidney Transplantation; D007687:Kidney Tubules, Proximal / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D011991:Receptors, Virus / Q000032:analysis*
chemical_list: C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus