Renal L-type fatty acid--binding protein in acute ischemic injury.
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.
Yamamoto
Tokunori
T
Department of Urology, University Hospital, Nagoya University, Nagoya, Japan 113-8655.
Noiri
Eisei
E
Ono
Yoshinari
Y
Doi
Kent
K
Negishi
Kousuke
K
Kamijo
Atsuko
A
Kimura
Kenjiro
K
Fujita
Toshiro
T
Kinukawa
Tsuneo
T
Taniguchi
Hideki
H
Nakamura
Kazuo
K
Goto
Momokazu
M
Shinozaki
Naoshi
N
Ohshima
Shinichi
S
Sugaya
Takeshi
T
D000818:Animals; D015415:Biomarkers / Q000652:urine; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000652:urine*; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008955:Models, Cardiovascular; D015427:Reperfusion Injury / Q000473:pathology / Q000652:urine*
D015415:Biomarkers; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins