To study the role of
erythropoietin (Epo) in the pathogenesis of
anemia in
acute renal failure (ARF), organ Epo
mRNA was measured by
RNase protection assay in rats with ARF induced by a one hour-occlusion of the left renal artery. Hematocrit was significantly decreased two hours, 24 hours and one week after renal artery occlusion. A significant reduction in serum
haptoglobin at two hours and an increase in serum LDH at 24 hours indicated that
hemolysis was the likely cause of the initial fall in hematocrit. However, despite the reduced hematocrit, serum Epo concentrations were not significantly different from controls, suggesting that the
anemia is maintained because of lack of an appropriate Epo response. Right renal Epo
mRNA levels were not significantly different in all groups, but Epo
mRNA levels in post-ischemic kidneys were 50 to 67% lower than in contralateral kidneys. However, Epo
mRNA in the post-ischemic kidney was increased sixfold by acute
hemorrhage, a rise comparable to the ninefold increase observed in contralateral kidneys. In ARF rats exposed to 7.5% O2 for four hours, right kidney Epo
mRNA increased 200-fold over normoxic levels, to a value similar to
sham-operated hypoxic controls. Epo
mRNA in the post-ischemic kidney also increased 200-fold, to 50% of the level in the contralateral kidney. Hepatic Epo
mRNA levels were elevated to comparable levels in both groups. In this ARF model, mild
anemia is associated with relative Epo deficiency. In the post-ischemic kidney, a substantial capacity for Epo production is retained but the sensitivity of the Epo response to blood
oxygen availability is significantly reduced.