END-STAGE RENAL-DISEASE FOLLOWING POLYCYTHEMIA-VERA - IN-VITRO AND IN-VIVO RESPONSE OF ERYTHROID PROGENITORS TO ERYTHROPOIETIN AND EFFECTS OF SERA ON NORMAL ERYTHROPOIESIS

We investigated the in vitro erythroid progenitor growth and the effec ts of sera on normal-marrow CFU-E (colony-forming units - erythroid) g rowth in 2 patients with renal failure on regular hemodialysis followi ng a prior history of polycythemia vera (PV), PV was diagnosed 3 and 1 1 years, respectively, before the development of terminal renal failur e. One of the patients had entered a spent phase of PV as characterize d by diffuse extensive myelofibrosis and anemia; the other also had mi ld myelofibrosis, The serum erythropoietin (EPO) levels were low or no rmal on serial measurements by radioimmunoassay. There was no correlat ion between the hematocrit values and serum EPO levels, EPO-independen t erythroid colonies were present in the cultures of bone marrow and p eripheral blood cells from both patients after renal failure in the an emic state. With the addition of various concentrations of EPO, the nu mber of erythroid colonies increased as the concentrations of EPO incr eased which was in accordance with the clinical observation that 1 pat ient with postpolycythemic myeloid metaplasia partially responded to r ecombinant human EPO therapy. In the EPO-dependent CFU-E assay, normal -marrow CFU-E numbers supported by 10% of the patient sera were less t han those by normal sera. In the absence of EPO in cultures, no erythr opoietic activity was found in the patients' sera. Our study on uremic patients with underlying PV showed that the biologic characteristics of autonomous erythroid progenitor growth for PV persisted during the spent phase and after the development of terminal renal failure with a nemia. The erythroid progenitors responded to EPO both in vitro and in vivo. Their sera exhibited an inhibiting effect on the growth of norm al-marrow erythroid progenitors.