Hormonal adjuvants for the treatment of renal anaemia

Hormonal adjuvants, besides being erythropoietic agents, broaden the spectrum of therapeutic options for the treatment of the anaemia of chronic kidney disease (CKD). Lowering elevated parathyroid hormone levels by oral calcium supplementation and phosphate restriction, by varying dialysate calcium concentrations, by administration of vitamin D3 derivatives and, in the near future, by treatment with calcimimetics may prove efficient in some patients to fight extensive requirements of erythropoietic agents. Clinical evidence for a principal role of secondary hyperparathyroidism in resistance to erythropoietin, however, is lacking. Active vitamin D3 derivatives, in addition to their beneficial effects on secondary hyperparathyroidism, appear to exert a direct, stimulatory action on erythroid precursor cells and possibly also an inhibitory action on collagen synthesis by bone marrow stromal cells. Growth hormone (GH) induces insulin-like growth factor (IGF)-1, which in turn counteracts apoptosis similarly to erythropoietin, and fosters proliferation of burst- and colony-forming units-erythroid (BFU-E, CFU-E). If erythropoietic agents improve survival of CKD patients, a similar benefit should apply for strategies that increase synthesis and bioavailabilty of IGF-1. The latter appears to be reduced in CKD patients, and zinc supplementation potentially enhances it via an increase in free IGF-1. Finally, androgens also exert anti-anaemic effects. Nandrolone decanoate constitutes the only androgen currently applicable for selected male dialysis patients over the age of 50 years. It should not be given to women, however, because of serious side effects. Collectively, hormonal interventions offer the potential to reduce requirements of erythropoietic agents, and some may also improve physical performance.