title: Kidney injury molecule-1 is an early noninvasive indicator for donor brain death-induced injury prior to kidney transplantation.
abstract: With more marginal deceased donors affecting graft viability, there is a need for specific parameters to assess kidney graft quality at the time of organ procurement in the deceased donor. Recently, kidney injury molecule-1 (Kim-1) was described as an early biomarker of renal proximal tubular damage. We assessed Kim-1 in a small animal brain death model as an early and noninvasive marker for donor-derived injury related to brain death and its sequelae, with subsequent confirmation in human donors. In rat kidney, real-time PCR revealed a 46-fold Kim-1 gene upregulation after 4 h of brain death. In situ hybridization showed proximal tubular Kim-1 localization, which was confirmed by immunohistochemistry. Also, Luminex assay showed a 6.6-fold Kim-1 rise in urine after 4 h of brain death. In human donors, 2.5-fold kidney injury molecule-1 (KIM-1) gene upregulation and 2-fold higher urine levels were found in donation after brain death (DBD) donors compared to living kidney donors. Multiple regression analysis showed that urinary KIM-1 at brain death diagnosis was a positive predictor of recipient serum creatinine, 14 days (p < 0.001) and 1 year (p < 0.05) after kidney transplantation. In conclusion, we think that Kim-1 is a promising novel marker for the early, organ specific and noninvasive detection of brain death-induced donor kidney damage.
authors.affiliation: Surgery Research Laboratory and Department of Surgery, University Medical Center Groningen, University of Groningen, The Netherlands. w.n.nijboer@chir.umcg.nl
authors.forename: W N
authors.initials: WN
authors.lastname: Nijboer
authors.forename: T A
authors.initials: TA
authors.lastname: Schuurs
authors.forename: J
authors.initials: J
authors.lastname: Damman
authors.forename: H
authors.initials: H
authors.lastname: van Goor
authors.forename: V S
authors.initials: VS
authors.lastname: Vaidya
authors.forename: J J Homan
authors.initials: JJ
authors.lastname: van der Heide
authors.forename: H G D
authors.initials: HG
authors.lastname: Leuvenink
authors.forename: J V
authors.initials: JV
authors.lastname: Bonventre
authors.forename: R J
authors.initials: RJ
authors.lastname: Ploeg
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001926:Brain Death / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival / Q000502:physiology; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011237:Predictive Value of Tests; D051381:Rats; D011916:Rats, Inbred F344; D011991:Receptors, Virus / Q000378:metabolism*; D012044:Regression Analysis; D009927:Tissue and Organ Procurement
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; C491143:HAVCR1 protein, human; C110936:Havcr1 protein, rat