title: Keratinocyte-derived chemokine is an early biomarker of ischemic acute kidney injury.
abstract: Renal ischemia-reperfusion injury (IRI) is the leading cause of acute kidney injury [AKI; acute renal failure (ARF)] in native kidneys and delayed graft function in deceased donor kidney transplants. Serum creatinine rises late after renal IRI, which results in delayed diagnosis. There is an important need to identify novel biomarkers for early diagnosis and prognosis in renal IRI. Given the inflammatory pathophysiology of renal IRI, we used a protein array to measure 18 cytokines and chemokines in a mouse model of renal IRI at 3, 24, and 72 h postischemia. A rise in renal keratinocyte-derived chemokine (KC) was the earliest and most consistent compared with other molecules, with 3-h postischemia values being 9- and 13-fold greater than sham and normal animals, respectively. Histological changes were evident within 1 h of IRI but serum creatinine only increased 24 h after IRI. With the use of an ELISA, KC levels in serum and urine were highest 3 h postischemia, well before a significant rise in serum creatinine. The human analog of KC, Gro-alpha, was markedly elevated in urine from humans who received deceased donor kidney transplants that required dialysis, compared with deceased donor kidney recipients with good graft function and live donor recipients with minimal ischemia. Measurement of KC and its human analog, Gro-alpha, could serve as a useful new biomarker for ischemic ARF.
authors.affiliation: Johns Hopkins Univ. School of Medicine, Ross 965, 720 Rutland Ave, Baltimore, MD 21205, USA.
authors.forename: Roshni R
authors.initials: RR
authors.lastname: Molls
authors.forename: Vladimir
authors.initials: V
authors.lastname: Savransky
authors.forename: Manchang
authors.initials: M
authors.lastname: Liu
authors.forename: Shannon
authors.initials: S
authors.lastname: Bevans
authors.forename: Tulsi
authors.initials: T
authors.lastname: Mehta
authors.forename: Rubin M
authors.initials: RM
authors.lastname: Tuder
authors.forename: Landon S
authors.initials: LS
authors.lastname: King
authors.forename: Hamid
authors.initials: H
authors.lastname: Rabb
mesh_terms: D000208:Acute Disease; D058186:Acute Kidney Injury; D000818:Animals; D015415:Biomarkers; D018925:Chemokines / Q000032:analysis*; D016207:Cytokines / Q000032:analysis; D003937:Diagnosis, Differential; D007511:Ischemia / Q000175:diagnosis*; D015603:Keratinocytes / Q000737:chemistry*; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011379:Prognosis; D015427:Reperfusion Injury
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines