Ischemic Renal Injury: Can Renal Anatomy and Associated Vascular Congestion Explain Why the Medulla and Not the Cortex Is Where the Trouble Starts?

The kidneys receive approximately 20% of cardiac output and have a low fractional oxygen extraction. Quite paradoxically, however, the kidneys are highly susceptible to ischemic injury (injury associated with inadequate blood supply), which is most evident in the renal medulla. The predominant proposal to explain this susceptibility has been a mismatch between oxygen supply and metabolic demand. It has been proposed that unlike the well-perfused renal cortex, the renal medulla normally operates just above the threshold for hypoxia and that further reductions in renal perfusion cause hypoxic injury in this metabolically active region. An alternative proposal is that the true cause of ischemic injury is not a simple mismatch between medullary metabolic demand and oxygen supply, but rather the susceptibility of the outer medulla to vascular congestion. The capillary plexus of the renal outer medullary region is especially prone to vascular congestion during periods of ischemia. It is the failure to restore the circulation to the outer medulla that mediates complete and prolonged ischemia to much of this region, leading to injury and tubular cell death. We suggest that greater emphasis on developing clinically useful methods to help prevent or reverse the congestion of the renal medullary vasculature may provide a means to reduce the incidence and cost of acute kidney injury.