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Decreased kidney oxygenation due to mitochondrial uncoupling: a mechanism to injury after renal transplantation (890.7)
Author(s) -
FriederichPersson Malou,
Papazova Diana,
Joles Jaap,
Verhaar Marianne
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.890.7
Subject(s) - renal function , transplantation , kidney , medicine , endocrinology , renal blood flow , oxygenation , chemistry , oxygen tension , urology , kidney transplantation , oxygen , organic chemistry
*Equal contribution The mechanisms to reduced graft function after renal transplantation are poorly understood. Mitochondrial uncoupling via uncoupling proteins (UCP) increases oxygen consumption and can contribute to the decreased kidney oxygen tension that is regarded as part of a common pathway to nephropathy. The aim was to investigate mitochondrial uncoupling, graft oxygenation and function after renal transplantation. Male Lewis rats were left untreated as controls (CON, N=6) or underwent syngenic renal transplantation (Tx, N=6). Tx was performed with end‐to‐end anastomoses of vessels and urether, with 30 min and 30‐40 min cold and warm ischemia time respectively and removal of right kidney. Two weeks after Tx, we measured renal function as glomerular filtration rate (GFR: inulin clearance), renal blood flow (RBF: PAH clearance/1‐hct) and kidney oxygen tension (pO2). Mitochondria uncoupling was evaluated in a separate cohort (6/group). Tx resulted in mitochondrial uncoupling evident as a larger decrease in oxygen consumption after UCP blockade (‐15.8±2.1 vs. ‐1.9±0.8 pmol O2/s p<0.05). Furthermore, Tx resulted in increased GFR (2.4±0.2 vs. 1.8±0.4 ml/min/kidney, P<0.05), RBF (14.4±1.4 vs. 11.4 ± 1.7 ml/min/kidney p<0.01), proteinuria (9±1 vs. 4±0 mg/day p<0.05) and decreased pO2 (. 30.3±12.6 vs. 58.8±15.3 µM p<0.01) but did not affect mean arterial pressure (98±11 vs. 99±5 mmHg ns). The present study demonstrates that mitochondrial uncoupling occurs early after Tx and is associated with decreased kidney oxygen tension despite hyperperfusion. This hypoxia may contribute to progressive damage in transplanted kidneys.