Original Paper

Nephron 1992:61:54 57

Valter Piazza Giuseppe Villa Franco Galli Siro Segagni Giacomo Bovio Francesco Poggio Loredana Picardi Alessandro Salvadeo

Recombinant Human Erythropoietin Reduces Free Erythrocyte Protoporphyrin Levels in Patients on Chronic Dialysis

Key Words


Erythropoietin Heme Hemodialysis Porphyrins

We studied the significance o f free erythrocyte protoporphyrin (FEP) in relation to iron status, aluminum levels and anemia in uremic patients on chronic dialysis. All but I patient showed high FEP values closely related to the degree of anemia. 1ncreased FEP levels are due to a defective heme synthesis, not related to iron deficiency or aluminum overload. Treatment of anemia with recombinant human erythropoietin reduced FEP values. We therefore hypothesize that recombinant human erythropoietin ameliorates an enzymatic defect in heme synthesis.

Introduction Uremic anemia may be efficiently treated with recombi­ nant human erythropoietin (rHuEPO) [1]. The hematopoie­ tic action of rHuEPO occurs in two ways: (1) by promoting differentiation o f erythroid stem cells into pronormoblasts; (2) by stimulating erythroid cells to produce hemoglobin [2]. Hemoglobin is a tetramer consisting o f 2 pairs of polypeptidic chains, each one covalently bonded to the heme group. Heme results from the reaction, catalyzed by ferrochelatase, of protoporphyrin IX with divalent Fe:+ ion. The amount of protoporphyrin IX produced by erythroid cells is usually slightly higher than that needed to synthesize heme; proto­ porphyrin IX in excess is called free erythrocyte protopor­

Accepted : August 16. 1991

phyrin (FEP). FEP increases in iron deficiency anemia [3] owing to a reduced availability o f iron for heme production. Therefore, increased FEP levels indicate low body iron stores, and the FEP value correlates with other Fe indicators such as serum ferritin (SF). Furthermore, FEP increases when ferrochelatase activity is reduced, as happens in pro­ toporphyria or in lead poisoning [3]. Chronic renal failure is associated with increased levels of porphyrins, and it is believed that high FEP values are related to the anemic condition o f these patients [4], The purpose of this paper is to investigate, in regularly dialyzed patients, the relation­ ships between FEP, iron levels, degree o f anemia and also to evaluate the changes induced in these parameters by rHu­ EPO treatment.

Valter Piuzza, M D Divisione di Nefrologia ed Emodialisi Fondazione Clinica del Lavoro v. Boezio 26.1-27100 Pavia (Italy)

Recombinant human erythropoietin reduces free erythrocyte protoporphyrin levels in patients on chronic dialysis.

We studied the significance of free erythrocyte protoporphyrin (FEP) in relation to iron status, aluminum levels and anemia in uremic patients on chro...
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