Selective anoxic injury to thick ascending limb: an anginal syndrome of the renal medulla?

Abstract

Cortico-medullary gradients of O2 availability within the renal parenchyma have been appreciated for some time, but not their pathophysiological significance. During isolated perfusion of the rat kidney with cell-free albumin-Ringer's medium, a specific anatomical lesion is consistently observed, confined to the medullary thick ascending limb of Henle's loop (mTAL), that progresses over 90 min from mitochondrial swelling to nuclear pyknosis and complete cellular disruption. The lesion is exaggerated by oxygen deprivation and ameliorated by increasing the oxygen content of the perfusion or by reducing the transport work of mTAL cells. Because of its anatomical location associated with a low O2 supply imposed by the medullary vascular system and its high rate of electrolyte transport, the mTAL appears to be exquisitely sensitive to O2 deprivation. The consequent anoxic lesion, resulting from an imbalance between O2 supply and demand, may have important implications for the understanding of ischemic renal injury.