Mechanism of action of androgens on the anemia associated with experimental chronic renal failure in the mouse

Anemia is a hallmark of chronic renal failure (CRF) which, if left untreated, is a major contributing factor to the high morbidity and mortality of this condition. This characteristically hypoproliferative anemia is due primarily to decreased erythropoietin (EPO) production by the diseased kidney. Currently, correction of the anemia with recombinant human EPO (r-HuEPO) constitutes the mainstay of management in patients with end-stage renal disease (ESRD).An alternative approach to the treatment of the anemia of CRF is the administration of androgens.My project utilized a well characterized mouse model of surgically-induced renal failure to study the mechanism(s) of androgen effect on the anemia of CRF. Recent experiments in this model revealed a dose-response to r-HuEPO similar to that in humans, absent EPO gene expression in the liver and full correction of the anemia of CRF by the administration of a combination of subtherapeutic doses of r-HuEPO and insulin-like growth factor-I (IGF-I), a known regulator of erythropoiesis in the normal physiological state.My hypothesis followed two lines of investigation: androgens may act to increase EPO production or they may increase production of IGF-I, thereby increasing extra-renal erythropoietic activity by either of the two hormones. (Abstract shortened by UMI.