Long-term effects of recombinant human erythropoietin therapy on growth hormone secretion in uremic patients undergoing peritoneal dialysis

Recombinant human erythropoietin (rhEPO) is being successfully used for the treatment of uremic anemia. Short-term studies have proved that correction of anemia with rhEPO therapy is accompanied by several changes in growth h ormone (GH) secretion in uremic patients. The present study aimed to assess the influence of lone-term rhEPO therapy on baseline and stimulated GH con centrations in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Seven well-nourished and clinically stable CAPD patients were studied. Ten normal subjects were studied as controls, GH re sponses to direct pituitary stimulation with OH-releasing hormone (GHRH) (1 00 mu g intravenously [IV]) and indirect hypothalamic stimulation with insu lin-induced hypoglycemia (0.1 U/kg body weight IV) and clonidine (0.15 mg/m (2) orally), were assessed before and after 3, 6, and 12 months of subcutan eously administered rhEPO therapy. After rhEPO administration, an increase of the hemoglobin concentration was observed in all patients and maintained at about 12 g/dL throughout the study period. rhEPO therapy did not induce any significant change in baseline concentrations of GH and insulin-like g rowth factor I. Correction of the anemia was accompanied by a clear increas e in the area under the curve (AUC) and the area above the baseline (AAB) o f GH secretion in response to GHRH stimulation. These changes were statisti cally significant after 3 and 6 months of therapy, although at 12 months no significant differences in relation to pretreatment values could be observ ed. rhEPO treatment was associated with a progressive decrement in the GH A UC and AAB in response to hypoglycemic challenge, reaching statistically si gnificant values at months 6 and 12. On the other hand, compared with the c ontrol group, GH responses to clonidine were blunted at the start of the st udy in CAPD patients, and rhEPO therapy was not accompanied by any modifica tion. In conclusion, long-term treatment with rhEPO in CAPD patients is ass ociated with complex and profound effects on somatotrope cell function, cha racterized by diverse effects on GH responses to stimuli that release GH th rough different mechanisms, Some of these rhEPO-induced alterations in soma totrope function are dependent on the duration of treatment. Copyright (C) 1999 by W.B. Saunders Company.