Acidosis and hypoxic medullary injury in the isolated perfused kidney

The effects of acidosis on renal function and morphology were examined in the isolated perfused rat kidney (IPK). Kidneys were perfused with oxygenated Krebs-Henseleit-albumin medium for 60 minutes at pH 7.4 or pH 7.0. At the lower pH, GFR was reduced by 25%, TRNa by 32% and oxygen consumption by 41% as compared to perfusion at pH 7.4 (all P less than 0.05). In addition, the usual hypoxic injury observed in the medullary thick ascending limb of the Loop of Henle (TAL) in the IPK at pH 7.4 (consisting of nuclear pyknosis and focal fragmentation necrosis) was reduced by acidosis from 62% to 14% of tubules involved (P less than 0.005). This cytoprotection was not the result of improved oxygenation since O2 delivery was actually slighty reduced at pH 7.0 compared to pH 7.4. Furthermore, acidosis was protective even after perfusion with non-oxygenated media (42% tubules damaged at pH 7.0 vs. 95% of tubules damaged at pH 7.4; P less than 0.01), making it very unlikely that the effect of acidosis is to improve TAL oxygenation. Since previous studies indicate that the TAL lesion is transport dependent and prevented in the non-filtering kidney, it was possible that the decrease in GFR associated with acidosis could account for decreased injury. The GFR was manipulated by alterations in perfusion pressure or albumin concentration, and no consistent relationship between the extent of injury and GFR could be shown at either pH over a wide range of GFR values. Therefore, acidosis protected the TAL from hypoxic injury by a mechanism apparently independent of oxygen or solute delivery.(ABSTRACT TRUNCATED AT 250 WORDS)