HFE genotype influences erythropoiesis support requirement in hemodialysis patients: a prospective study.
OBJECTIVE
HFE protein controls iron absorption and cycling, and HFE mutations influence iron status. The aim was to evaluate the effect of the HFE genotype on the need for iron and erythropoietin in Italian hemodialysis patients.


METHODS
Ninety-six prevalent patients were evaluated at the time of enrolment and prospectively followed for 3 years. Patients were given r-HuEPO and Fe3+-gluconate according to guidelines. The HFE genotype was determined by restriction analysis.


RESULTS
Three patients (3%) carried the C282Y mutation, 4 (4%) were homozygous and 18 (19%) heterozygous for the H63D mutation, and 71 (74%) were negative for both. At enrolment, subjects positive for HFE mutations had higher iron stores (ferritin 617 +/- 663 vs. 423 +/- 386 ng/ml, p = 0.05), were receiving less iron (82.5 +/- 66 vs. 110 +/- 154 mg/month, p = 0.05) and a lower r-HuEPO dosage (98 +/- 83 vs. 142 +/- 138 U/kg/week, p = 0.03). Consistently during the study period, patients positive for HFE mutations received a lower amount of r-HuEPO (94.5 +/- 63 vs. 186 +/- 344 U/kg/week, p = 0.01) and iron (97 +/- 63 vs. 121 +/- 68 mg/month, p = 0.07). Upon Cox regression analysis, after adjustment for confounding variables, the presence of HFE mutations was associated with a reduced risk of death (HR 0.6, 95% CI 0.34-1.03, p = 0.06).


CONCLUSIONS
HFE mutations reduce the amount of r-HuEPO and iron necessary to support erythropoiesis in hemodialysis.
Valenti
Luca
L
Department of Internal Medicine, University of Milan, Ospedale Policlinico Mangiagalli e Regina Elena Fondazione IRCCS, Milan, Italy.
Valenti
Giovanni
G
Como
Giovanna
G
Santorelli
Gennaro
G
Dongiovanni
Paola
P
Rametta
Raffaela
R
Fracanzani
Anna Ludovica
AL
Tavazzi
Dario
D
Messa
Pier Giorgio
PG
Fargion
Silvia
S
D000368:Aged; D004920:Erythropoiesis; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism; D007558:Italy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D011994:Recombinant Proteins; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000235:genetics* / Q000628:therapy
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron