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Renal L-Type Fatty Acid–Binding Protein in Acute Ischemic Injury

Tokunori Yamamoto^*, Eisei Noiri, Yoshinari Ono^*, Kent Doi, Kousuke Negishi, Atsuko Kamijo, Kenjiro Kimura, Toshiro Fujita, Tsuneo Kinukawa, Hideki Taniguchi^||, Kazuo Nakamura^¶, Momokazu Goto^*, Naoshi Shinozaki^**, Shinichi Ohshima and Takeshi Sugaya^||,**

^* Department of Urology, University Hospital, Nagoya University, Nagoya; Departments of Nephrology and Endocrinology, Hemodialysis and Apheresis, University Hospital, and Center of NanoBio Integration, University of Tokyo, Tokyo; Department of Nephrology and Hypertension, St. Marianna University, Kawasaki; Department of Urology, Chukyo Hospital, Nagoya; ^|| Center for Developmental Biology, Riken, Kobe; ^¶ CMIC Co., Ltd., Tokyo; ^** Cornea Center, Tokyo Dental College Ichikawa General Hospital, Tokyo; and National Center for Geriatrics and Gerontology, Obu, Japan

Correspondence: Dr. Eisei Noiri, 107 Lab, Nephrology, University Hospital, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, Japan 113-8655. Phone/Fax: 81-3-5814-8696; E-mail: noiri-1im{at}h.u-tokyo.ac.jp

Received for publication January 23, 2007. Accepted for publication June 14, 2007.

Fatty acid–binding proteins (FABPs) bind unsaturated fatty acids and lipid peroxidation products during tissue injury from hypoxia. We evaluated the potential role of L-type FABP (L-FABP) as a biomarker of renal ischemia in both human kidney transplant patients and animal models. Urinary L-FABP levels were measured in the first urine produced from 12 living-related kidney transplant patients immediately after reperfusion of their transplanted organs, and intravital video analysis of peritubular capillary blood flow was performed simultaneously. A significant direct correlation was found between urinary L-FABP level and both peritubular capillary blood flow and the ischemic time of the transplanted kidney (both P < 0.0001), as well as hospital stay (P < 0.05). In human-L-FABP transgenic mice subjected to ischemia-reperfusion injury, immunohistological analyses demonstrated the transition of L-FABP from the cytoplasm of proximal tubular cells to the tubular lumen. In addition, after injury, these transgenic mice demonstrated lower blood urea nitrogen levels and less histological injury than injured wild-type mice, likely due to a reduction of tissue hypoxia. In vitro experiments using a stable cell line of mouse proximal tubule cells transfected with h-L-FABP cDNA showed reduction of oxidative stress during hypoxia compared to untransfected cells. Taken together, these data show that increased urinary L-FABP after ischemic-reperfusion injury may find future use as a biomarker of acute ischemic injury.

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				J. M. Hofstra, J. K. J. Deegens, E. J. Steenbergen, and J. F. M. Wetzels Urinary excretion of fatty acid-binding proteins in idiopathic membranous nephropathy Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3160 - 3165. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673