Unexpected renal actions of erythropoietin.

Erythropoietin (EPO) in the renal cortex is synthesized by fibroblast-like cells that are in direct contact with capillaries and adjacent tubular cells. Prompted by this anatomical relationship, we asked whether renal cells express EPO receptors (EPORs) through which EPO could act as a renotropic cytokine. We found that all regions of human, rat and mouse kidney, mesangial and proximal and distal tubular cells express authentic EPORs. Similar EPOR expression was detected in kidney cancer cells, and in cyst epithelia from polycystic kidneys. In vitro, EPO stimulated mitogenesis in all normal and malignant cells, and cell survival and motogenesis in injured tubular cells. Since the normal kidney is essentially unresponsive to EPO, we hypothesized that EPO's cytokine effects in the kidney are revealed when tubular cells are induced to proliferate by a prior insult, as occurs in acute renal failure. Accordingly, we found that EPO treatment of rats with 'ischemic' acute renal failure afforded renoprotection and accelerated functional recovery.