Exceptionally high serum erythropoietin activity in an anephric patient with severe anemia

Abstract

An exceptionally high serum erythropoietin (EPO) activity was documented in an anephric patient with severe anemia who required transfusions every 4 weeks. The patient's serum EPO was comparable to normal human urinary EPO in the polycythemic mouse assay and was neutralized by an antiserum against EPO. The patient's serum inhibited EPO stimulated-heme synthesis by normal human marrow cells in vitro. This finding suggests that an inhibitor played an important role in causing the anemia of this uremic patient.

Controversies in renal anemia management

“…6 Though both animal and human studies have found that impairment of erythropoiesis in uremia is attributable in part to nitrogenous inhibitors, [43][44][45][46][47][48][49][50][51][52][53] these inhibitors have not been identified. Candidate substances include polyamines, spermine, cytokines from T cells, and N-acetyl-seryl-aspartyllysyl-proline (AcSDKP).…”

“…Persistent anemia in chronic renal failure despite high serum levels of erythropoietin (30-100 mU/mL). 48,51 . Uremic anemia improved with initiation of dialysis or with better dialysis.…”

Evidence that Adequacy of Dialysis Modulates Uremic Anemia

“…Though both animal and human studies have found impairment of erythropoiesis in uremia attributed in part to nitrogenous inhibitors of erythropoiesis [29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39], but like the elusive ‘uremic toxin’, these inhibitors have not been identified. They lie in the range of ‘middle molecules’ [33]and candidate substances include polyamines and spermine [35].…”

“…Clinical support for existence of uremic inhibitors of erythropoiesis included the findings that (a) an infusion of EPO-rich plasma from a patient with aplastic anemia resulted in reticulocytosis in normal renal function but not in severe renal failure [34], and (b) anemia persisted in some patients with chronic renal failure despite high serum levels of EPO (30–100 mU/ml), suggesting that erythroid cells are unable to respond to circulating EPO [34, 37]. …”

Is the Erythropoietin-Hematocrit Feedback Control Operative in Chronic Renal Failure?

“…Extremely high as well as very low or deficient EP levels in the pres ence of low hematocrit (HCT) values have been reported [1,3,5,7,9,10,14,21,24,25], The functional role of EP in chronic renal failure could best be elucidated if the physi ologic feedback control mechanism between the HCT and EP was shown to be operative in the terminal stage of kidney diseases. We investigated this question by studying patients on chronic intermittent hemodialysis treatment who had low HCT values representing a strong stimulus to their erythropoiesis; subsequently, we transfused these patients with red blood cell (RBC) concentrates in order to force a strong suppressive effect upon their erythropoietic tissues.…”