RENIN-ANGIOTENSIN SYSTEM STIMULATES ERYTHROPOIETIN SECRETION IN CHRONIC-HEMODIALYSIS PATIENTS

A series of observations suggests an interrelationship between the ren in-angiotensin system (RAS) and erythropoietin (EPO) secretion. To fur ther evaluate the role of RAS in erythropoiesis of chronic hemodialysi s patients, rye studied two groups of such patients: Group A consisted of 16 patients (14 male and 2 female, 54.7 +/- 3.3 years old), who ma intained a target hematocrit value of 0.30 (0.32 +/- 0.01), without re combinant human EPO (rhEPO) supplementation. Group B consisted of 14 p atients (7 male and 7 female, 50 +/- 5.3 years old), who required subc utaneous injections of rhEPO (90.8 +/- 10 IU.kg(-1).week(-1)), to main tain the same target hematocrit value of 0.30 (30 +/- 0.01). Plasma re nin activity (PRA) was found to be the major feature to distinguish pa tients in these two Groups and it was five times higher in Group A (10 +/- 2 ng.ml(-1).h(-1)) compared to Group B patients (1.8 +/- 0.6 ng.m l(-1).h(-1)) (p <0.001). Moreover, activation of RAS in Group A patien ts by volume depletion (2.2 +/- 0.2l) during hemodialysis resulted in a 118 +/- 33 percent increment of PRA (p <0.01) which was accompanied by a 69 +/- 25 percent increment of serum EPO levels (p <0.05). Repeti tion of the same protocol after inhibiting the converting enzyme with 50 mg of Captopril prior to dialysis session, resulted in a 315 +/- 64 percent increment of PRA (p <0.001), while at the same time completel y blocked the expected rise in serum EPO levels (1.25 +/- 12.5 percent increment). These findings provide persuasive evidence strongly linki ng EPO secretion to RAS activation in chronic hemodialysis patients.