Experimental Models of Acute Renal Failure and Erythropoietin: What Evidence of a Direct Effect?

Abstract

The kidney can achieve a structural and functional recovery after the damage induced by ischemia and reperfusion. This is due to the regeneration of epithelial tubular cells, the intervention of immature cells mainly localized in the medulla, and a small number of bone marrow-derived stem cells. In many instances, however, recovery is delayed or does not occur at all. The mechanisms allowing the renal cells to de-differentiate still need to be clarified in order to find a therapeutic approach that can amplify this ability and then stop the fibroid involution and the progression toward renal failure. Several authors have hypothesized a protective effect of EPO against ischemic and cytotoxic renal damage and observed that patients precociously treated with EPO showed a slower progression of renal failure. EPO has been demonstrated to have proliferative and anti-apoptotic effects in ischemia-reperfusion models in the brain and cell cultures. Moreover, EPO can mobilize stem cells and increase the plasmatic levels and the renal expression of VEGF. These effects seem to be dose-dependent and could be due to the activation of signal transduction systems, like Jak and STAT. In the presence of high doses of exogenous EPO or during the treatment with long-acting EPO-like molecules, non-specific receptors may be activated through a low-affinity link. Further investigations are needed to determine new therapeutic applications for EPO and other analogous hormones. Very long-acting molecules or molecules with cyto-protective but no erythropoietic effect may represent useful tools in the study of the molecular mechanisms underlying EPO's action and may have a rapid and safe therapeutic application.

Keywords:

• apoptosis
• erythropoietin
• JAK
• renal failure
• STAT

Notes

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