A model of hypoxic renal failure

Abstract

Models of ischemic acute renal failure (ARF) must consider the combination of tissue hypoxia, insufficient nutrient flow, and anaerobic waste product accumulation. This study utilized isolated perfused rat kidneys to characterize the renal response to a graded hypoxic insult while maintaining flow. Kidneys were perfused at 37°C with an asanguineous Krebs-buffered saline. After a 40-min baseline period, 10 or 30 min of hypoxia was rapidly achieved by reducing perfusate oxygen tension from approximately 550 to 50 mm Hg. Ten minutes of hypoxia resulted in tubular dysfunction evidenced by a 50% increase in urine flow (UV) and a 10% decrease in percent sodium reabsorption (%Na). Glomerular filtration rate (GFR) decreased by 40% during 10 min of hypoxia and returned to control levels after reoxygenation. Thirty minutes of hypoxia caused an irreversible 85% decrease in GFR accompanied by a 50% decrease in UV. This insult also caused more severe tubular dysfunction evidenced by a 20% decrease in %Na and a 35% decrease in oxygen consumption. These results demonstrate a spectrum of renal dysfunction that corresponds to the clinical spectrum from nonoliguric to oliguric ARF. This model of hypoxic ARF allows more specific investigation into the hypoxic component of postischemic renal dysfunction.