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

Abstract

We investigated the in vitro erythroid progenitor growth and the effects of sera on normal-marrow CFU-E (colony-forming units – erythroid) growth in 2 patients with renal failure on regular hemodialysis following a prior history of polycythemia vera (PV). PV was diagnosed 3 and 11 years, respectively, before the development of terminal renal failure. One of the patients had entered a spent phase of PV as characterized by diffuse extensive myelofibrosis and anemia; the other also had mild myelofibrosis. The serum erythropoietin (EPO) levels were low or normal on serial measurements by radioimmunoassay. There was no correlation between the hematocrit values and serum EPO levels. EPO-independent erythroid colonies were present in the cultures of bone marrow and peripheral blood cells from both patients after renal failure in the anemic state. With the addition of various concentrations of EPO, the number of erythroid colonies increased as the concentrations of EPO increased which was in accordance with the clinical observation that 1 patient with postpolycythemic myeloid metaplasia partially responded to recombinant human EPO therapy. In the EPO-dependent CFU-E assay, normal-marrow CFU-E numbers supported by 10% of the patient sera were less than those by normal sera. In the absence of EPO in cultures, no erythropoietic 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 anemia. The erythroid progenitors responded to EPO both in vitro and in vivo. Their sera exhibited an inhibiting effect on the growth of normal-marrow erythroid progenitors.

Polycythemia vera Concurrent with Chronic Renal Failure

“…[2,3]. On the other hand, it was also reported that exogenous EPO administration enhanced the erythropoiesis in this condition [1,4,5]. The data from our patient show that the hemoglobin values in PV concurrent with chronic renal failure are affected by lack of EPO.…”

“…Dear Sir, Recently, it was reported that there were 9 polycythemia vera (PV) cases associated with end-stage renal disease (ESRD) [1]. Of them, 2 had PV and ESRD at the time of diagnosis, 3 were on regular dialysis treatment before the diagnosis of PV, and 4 developed ESRD after PV diagnosis.…”

Postmortem serum erythropoietin levels in establishing the cause of death and survival time at medicolegal autopsy

“…Under these conditions, uremic patients under artificial hemodialysis with medical administration of an EPO agent showed a markedly high serum EPO level of >1,000 mU/ml, independent of the cause of death and survival time, indicating interference due to medical intervention before death. Such findings may be seen for patients within about 12 h after intravenous injection of an EPO agent when the elimination rate is considered [31,32].…”

Excessive erythrocytosis in adult mice overexpressing erythropoietin leads to hepatic, renal, neuronal, and muscular degeneration

“…Data from animal models have shown that reduction in nephron mass exposes the remaining nephrons to adaptive hemodynamic changes that are intended to sustain renal function acutely but may be detrimental for longer time periods (35). Other reports suggest that excessive erythrocytosis plays a role in the development of chronic renal failure in patients with preexisting polycythemia vera (40,41). On the other hand, patients with chronic mountain sickness at high altitude showed reduced kidney plasma flow and increased filtration fraction as hematocrit rose (22,25).…”