Erythrocytes alter the pattern of renal hypoxic injury: predominance of proximal tubular injury with moderate hypoxia.
Endre ZH., Ratcliffe PJ., Tange JD., Ferguson DJ., Radda GK., Ledingham JG.
1. The distribution of morphological injury was assessed qualitatively and quantitatively in the perfused rat kidney in vitro at controlled rates of oxygen delivery in the presence of low concentrations of erythrocytes. 2. In control kidneys (total oxygen delivery approximately 32 mumol/min per kidney) no injury was seen in the medullary thick ascending limb of Henle's loop (MTAL) whilst 11 +/- 5(SD)% of proximal tubules sustained damage. 3. Mild hypoxia (total oxygen delivery approximately 28 mumol/min per kidney) produced little or no injury to MTAL, namely 6 +/- 4(SD)% and 3 +/- 3% of tubules damaged, respectively. In contrast, both groups sustained extensive damage to proximal tubules, averaging 46 +/- 13% (P less than 0.01 vs control) and 84 +/- 14% (P less than 0.001 vs control), respectively. This damage was equally distributed between the superficial and deep cortex. 4. Comparison with morphometric data obtained previously from cell-free-perfused rat kidneys [P.J. Ratcliffe, Z. H. Endre, S. J. Scheinman, J. D. Tange, J. G. G. Ledingham & G. K. Radda (1988) Clinical Science 74, 437-448] showed that (a) erythrocytes prevent hypoxic damage to the MTAL at mild and moderate levels of hypoxia; (b) when oxygen delivery rates are matched between cell-free- and erythrocyte-perfused kidneys, proximal tubular injury is greater in the presence of erythrocytes; (c) when arterial partial pressure of oxygen is matched between cell-free- and erythrocyte-perfused kidneys, the degree of proximal tubular injury is similar. 5. The data suggest that the proximal tubule and not the MTAL is the nephron segment most at risk of hypoxic injury in vitro.