BACKGROUND: Ischemic nephropathy describes progressive renal failure, defined by significantly reduced glomerular filtration rate, and may be due to renal artery stenosis(RAS), a narrowing of the renal artery. It is unclear if ischemia is present during RAS since a decrease in renal blood flow (RBF), O₂ delivery, and O₂ consumption occur. The present study tests the hypothesis that despite proportional changes in whole kidney O₂ delivery and consumption, acute progressive RAS leads to decreases in regional renal tissue O₂. METHODS: Unilateral acute RAS was induced in 8 pigs with an extra-vascular cuff. RBF was measured with an ultrasound flow probe. Cortical and medullary tissue oxygen (P_tO₂) of the stenotic kidney was measured continuously with sensors during baseline, 3 sequentially graded decreases in RBF, and recovery. RESULTS: O₂ consumption decreased proportionally to O₂ delivery during the graded stenosis (19±10.8, 48.2±9.1, 58.9±4.7 vs 15.1±5, 35.4±3.5, 57±2.3% respectively) while arterial venous O₂ differences were unchanged. Acute RAS produced a sharp reduction in O₂ efficiency for sodium reabsorption (p<0.01). Cortical P_tO₂ decreases are exceeded by medullary decreases during stenosis (34.8±1.3%). CONCLUSIONS: Decreases in tissue oxygenation, more pronounced in the medulla than the cortex, occur despite proportional reductions in O₂ delivery and consumption. This demonstrates for the first time hypoxia is present in the early stages of RAS, and suggests a role for hypoxia in the pathophysiology of this disease. Furthermore, the notion that arterio venous shunting and increased stoichiometric energy requirements are potential contributors towards ensuing hypoxia with graded and progressive acute RAS cannot be excluded.