Clinical use of erythropoietin in chronic kidney disease: outcomes and future prospects.

The introduction of erythropoietin (Epo) in clinical practice, more than two decades ago, altered completely the management of patients with chronic kidney disease (CKD). The successful correction of anemia of CKD has resulted in reduction of associated morbidity and improvement of functionality, exercise tolerance, cognitive function and overall quality of life. Moreover, significant reduction of cardiovascular morbidity and mortality has occurred. Recently, large randomized clinical studies suggested that administration of Epo targeting at complete anemia correction is accompanied by significant increase of morbidity and mortality, compared to partial anemia correction. This observation has led to thorough investigation of the mechanisms of Epo actions and the possible contribution of other parameters including iron availability, comorbidities and resistance or hyporesponsiveness to Epo. In this context, it has been proposed that high doses of Epo are likely to exert toxic effects and pleiotropic systemic actions. Recognition of the extra-hematopoietic biologic actions of erythropoietin is a result of the better understanding of its interaction with Epo receptors in several tissues and organ systems, during fetal development as well as in the adult organism. More specifically, antiapoptotic, anti- inflammatory, angiogenetic and cytoprotective effects have been revealed in the kidneys, cardiovascular system, brain and retina. Until future studies are able to clarify the multiple beneficial or unfavorable effects of Epo, it is advisable to remain prudent in its administration, yet optimistic about its possible contribution in a number of pathologic conditions.