Alteration in renal organic anion transporter 1 after ischemia/reperfusion in cadaveric renal allografts.
We have previously shown that postischemic injury to renal allografts results in profound impairment of p-aminohippuric acid (PAH) extraction. To elucidate the cellular integrity of the human organic anion transporter 1 (hOAT1) in postischemic acute renal failure (ARF), immunohistochemical analysis of hOAT1 was performed in cadaveric renal allografts using confocal microscopy for three-dimensional reconstruction of serial optical images. Biopsy samples were obtained from 10 cadaveric renal allografts 1 hr after reperfusion during transplant operation. Control tissues were obtained from four living donors of healthy kidneys immediately before an arterial clamp was applied to the renal artery. Control tissues demonstrated hOAT1 distributed to basolateral membrane of proximal tubule cells. In contrast, maldistribution of hOAT1 to cytoplasm and/or diminution of the protein was noted in cadaveric allografts. Characteristics of maldistribution were variable: disappearance of lateral distribution, diffuse cytoplasmic aggregates, apical cytoplasmic aggregates, and disappearance of the staining. In addition, iothalamate and PAH clearances were performed on posttransplant days 3-7 in 18 recipients of a cadaveric renal allograft. PAH clearance was depressed <250 ml/min in all but three subjects. We conclude that reperfused, transplanted kidneys exhibit maldistribution of hOAT1 in proximal tubule cells, resulting in impairment of PAH clearance. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.
Kwon
Osun
O
Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, USA. okwon@psu.edu
Hong
Seok-Min
SM
Blouch
Kristina
K
D000328:Adult; D002102:Cadaver; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007483:Iothalamic Acid / Q000493:pharmacokinetics; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D016030:Kidney Transplantation / Q000379:methods*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D019520:Living Donors; D008297:Male; D008657:Metabolic Clearance Rate; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D027362:Organic Anion Transport Protein 1 / Q000032:analysis*; D015424:Reperfusion; D014019:Tissue Donors; D014184:Transplantation, Homologous; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D027362:Organic Anion Transport Protein 1; D007483:Iothalamic Acid; D010130:p-Aminohippuric Acid