Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension
2015 (English)In: American Journal of Physiology - Renal Physiology, ISSN 0363-6127, E-ISSN 1522-1466, Vol. 308, no 1, F22-F28 p.Article in journal (Refereed) Published
Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (PO2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney hypoxia. Lewis rats underwent syngenic renal transplantation (TX) and contralateral nephrectomy. Controls were uninephrectomized (1K-CON) or left untreated (2K-CON). After 7 days, urinary excretion of protein and thiobarbituric acid-reactive substances were measured, and after 14 days glomerular filtration rate (GFR), renal blood flow, whole kidney QO(2), cortical PO2, kidney cortex mitochondrial uncoupling, renal oxidative damage, and tubulointerstitial injury were assessed. TX, compared with 1K-CON, resulted in mitochondrial uncoupling mediated via uncoupling protein-2 (16 +/- 3.3 vs. 0.9 +/- 0.4 pmol O-2.s(-1) .mg protein(-1), P < 0.05) and increased whole kidney Q(O2) (55 +/- 16 vs. 33 +/- 10 mu mol O-2/min, P < 0.05). Corticomedullary P-O2 was lower in TX compared with 1K-CON (30 +/- 13 vs. 47 +/- 4 mu M, P < 0.05) whereas no significant difference was observed between 2K-CON and 1K-CON rats. Proteinuria, oxidative damage, and the tubulointerstitial injury score were not significantly different in 1K-CON and TX. Treatment of donors for 5 days with mito-TEMPO reduced mitochondrial uncoupling but did not affect renal hemodynamics, Q(O2), P-O2, or injury. Collectively, our results demonstrate increased mitochondrial uncoupling as an early event after experimental renal transplantation associated with increased oxygen consumption and kidney hypoxia in the absence of increases in markers of damage.
Place, publisher, year, edition, pages
2015. Vol. 308, no 1, F22-F28 p.
mitochondrial uncoupling, oxidative damage, transplantation, hypoxia
Physiology Urology and Nephrology
IdentifiersURN: urn:nbn:se:uu:diva-243435DOI: 10.1152/ajprenal.00278.2014ISI: 000347229000003OAI: oai:DiVA.org:uu-243435DiVA: diva2:788681