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Mitterbauer, C; Schwarz, C; Hauser, P; Steininger, R; Regele, HM; Rosenkranz, A; Oberbauer, R.
Impaired tubulointerstitial expression of endothelin-1 and nitric oxide isoforms in donor kidney biopsies with postischemic acute renal failure.
Transplantation. 2003; 76(4):715-720 Doi: 10.1097/01.TP.0000082820.13813.19
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Co-authors Med Uni Graz: Rosenkranz Alexander
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Abstract:: Background. About 30% of cadaveric renal allografts, but almost never living-donor kidneys, develop postischemic acute renal-transplant failure (ARF). We therefore quantified the expression of essential reperfusion regulators in different compartments of cadaveric and living-donor kidney biopsies. Methods. Specimens were obtained from donor kidneys at the end of the cold ischemia time before implantation and categorized into three groups according to donor source and early posttransplant function. Ten living-donor biopsies (LIV) were compared with nine cadaveric kidney biopsies (CAD) with primary posttransplant function (CAD-PF) and to nine with ARF (CAD-ARF). Laser capture microdissection was used to isolate glomeruli from tubulointerstitium. The gene expression of intercellular adhesion molecule (ICAM)-1, interleukin (IL)-1beta, endothelin (ET)-1, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) was quantified in glomeruli and tubulointerstitium by real-time polymerase chain reaction (TaqMan). Results. Tubulointerstitial areas of all CAD kidneys revealed significantly lower mRNA levels of all investigated genes compared with LIV. Tubulointerstitial ET-1, iNOS, and eNOS in CAD-ARF averaged only half of the expression in CAD-PF kidneys. ICAM-1 and IL-1beta mRNA concentrations were equal in CAD-PF and CAD-ARF. Glomerular expression of the investigated genes was equal in CAD and LIV kidneys with the exception of ICAM-1 and ET-1, which were two times higher in CAD-PF compared with LIV and CAD-ARF. Conclusion. These data suggest that CAD compared with LIV kidneys have an impaired expression of immune and vasoregulatory genes in the tubulointerstitium, which may represent reduced cellular vitality and capacity to adaptation. The observed further reduction of ET-1, iNOS, and eNOS expression in CAD-ARF might contribute to reperfusion injury and delayed allograft function.
Find related publications in this database (using NLM MeSH Indexing): Acute Kidney Injury - metabolism; Adult -; Biopsy -; Endothelin-1 - genetics; Gene Expression -; Humans -; Intercellular Adhesion Molecule-1 - genetics; Interleukin-1 - genetics; Ischemia - metabolism; Kidney - blood supply Kidney - metabolism; Middle Aged -; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II -; Nitric Oxide Synthase Type III -; RNA, Messenger - analysis; Tissue Donors -; Transplantation, Homologous -