Renal hypoxia due to increased oxygen metabolism is an independent pathway to nephropathy (890.6)

Abstract

The proposed pathways for the development of nephropathy are many and likely to be complex and overlapping. Recent literature strongly supports a role of renal tissue hypoxia as a pathway to nephropathy but the evidence remains inconclusive as the role of hypoxia cannot be separated from confounding factors such as hyperglycemia, hypertension and oxidative stress. By increasing kidney oxygen consumption (QO2) using triodothyronine (T3) we aimed to investigate the role of renal hypoxia per se for the development of nephropathy.Normoglycemic Sprague‐Dawley rats were treated with T3 (10 mg/kg bw/day) for 56 days. Thereafter, glomerular filtration rate (GFR), renal blood flow (RBF), total kidney QO2, kidney oxygen tension (pO2, Clark‐type oxygen electrodes) proteinuria, oxidative stress and histological alterations were evaluated and compared to corresponding controls.T3 increased kidney QO2 (18±2 vs. 11±1 µmol/min/kidney, p<0.05) and decreased kidney pO2 (27±1 vs. 44±1 mmHg, p<0.05). Furthermore, T3 resulted in proteinuria (74±6 vs. 54±5 µg/min/kidney, p<0.05) and four of eight T3‐treated rats, but none of the controls, presented with focal tubulointerstitial fibrosis. GFR (1.4±0.2 vs. 1.5±0.2 ml/min), RBF (12.7±1.6 vs. 11.1±0.8 ml/min), TBARS (15±2 vs. 16±3 fmol/min/kidney) and blood glucose (4.8±0.2 vs. 5.1±0.2 mM) were unaffected by T3. The detected mitochondrial uncoupling and increased ATP synthesis provide a mechanistic explanation for the increased kidney QO2.In conclusion, the present study adds further evidence in support of renal tissue hypoxia as an independent pathway to nephropathy.