GROWTH-HORMONE RESPONSES TO GROWTH HORMONE-RELEASING HORMONE AND CLONIDINE BEFORE AND AFTER ERYTHROPOIETIN THERAPY IN CAPD PATIENTS

Correction of anemia with recombinant human erythropoietin (rhEPO) in patients with endstage renal disease has been associated with improvem ent of several abnormalities in hypothalamo-hypophyseal functions. The aim of the present work was to evaluate the growth hormone (GH) respo nses to GH-releasing hormone (GHRH) and clonidine stimulation, as well as the baseline concentrations of insulin-like growth factor I (IGF-I ), before and after the correction of anemia with rhEPO in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis ( CAPD). Nine clinically stable patients(1 male, 8 female; mean age 55.4 years; mean duration of CAPD 14.1 months) were studied. Twelve normal volunteers were studied as controls. GHRH and clonidine stimulation t ests were performed prior to starting rhEPO and again after partial co rrection of anemia with rhEPO therapy (60-130 U/ kg/week, s.c., for 12 weeks). Blood samples for GH were collected during 2 h after GHRH (10 0 mu g i.v. in bolus) or clonidine (0.15 mg/m(2), p.o.) administration . In basal plasma samples IGF-I concentrations were also measured. Mea n (+/- SEM) blood hemoglobin concentration rose from 5.32 +/- 0.25 to 7.22 +/- 0.25 mmol/l (p < 0.001) after rhEPO treatment. GH responses t o GHRH were characterized by marked differences in single patients whe n compared with the control group. However, the GH peak and the area u nder the secretory curves (AUG) of GH responses in CAPD patients (9.89 +/- 4.01 mu g/l and 15.06 +/- 6.02 mu g . h/l, respectively) did not differ from those obtained in control subjects (14.58 +/- 3.25 mu g/l and 16.94 +/- 4.31 mu g . h/l, respectively). The study after correcti on of anemia showed an evident potentiation of CH values that reached statistically significant values at 60 and 90 min. GH AUC after rhEPO therapy rose to 25.61 +/- 9.25 mu g . h/l (p = 0.01). In control subje cts, clonidine administration was followed by a GH release that reache d a maximum at 90 min (7.67 +/- 2.24 mu g/l). However, CAPD patients e xhibited a blunted response to clonidine both before (2.00 +/- 0.78 mu g/l) and after (2.78 +/- 0.76 mu g/l, NS) correction of the anemia wi th rhEPO. On the other hand, IGF-I concentrations after rhEPO therapy (32.05 +/- 5.52 nmol/l) were not significantly different from those fo und prior to starting therapy (38.13 +/- 8.44 nmol/l). In conclusion, these results suggest that correction of the anemia with rhEPO therapy potentiates GH responses to direct pitiutary stimulation with GHRH al though it is unable to restore the blunted response of GH to clonidine that is found in CAPD patients.