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Am J Physiol Renal Physiol (December 20, 2005). doi:10.1152/ajprenal.00342.2005
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Submitted on August 23, 2005
Accepted on December 14, 2005

Keratinocyte-derived chemokine is an early biomarker of ischemic acute kidney injury

Roshni R. Molls1, Vladimir Savransky1, Manchang Liu1, Shannon Bevans1, Tulsi Mehta1, Rubin M. Tuder2, Landon S. King3, and Hamid Rabb1*

1 Department of Medicine - Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
2 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
3 Department of Medicine - Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

* To whom correspondence should be addressed. E-mail: hrabb1{at}jhmi.edu.

Renal ischemia reperfusion injury (IRI) is the leading cause of acute kidney injury (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 to other molecules, with 3 h postischemia values being 9 and 13 fold greater than sham and normal animals, respectively. Histologic changes were evident within 1 h of IRI but serum creatinine only increased 24 h after IRI. Using an ELISA, KC levels in serum and urine were highest 3 h postischemia, well before a significant rise in serum creatinine. The human analogue of KC, Gro-{alpha} was markedly elevated in urine from humans who received deceased donor kidney transplants that required dialysis, compared to deceased donor kidney recipients with good graft function and live donor recipients with minimal ischemia. Measurement of KC and its human analogue, Gro-{alpha}, could serve as a useful new biomarker for ischemic ARF.




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