title: Effect of angiotensin-converting enzyme gene insertion/deletion polymorphism and angiotensin-converting enzyme inhibition on erythropoiesis in patients on haemodialysis.
abstract: BACKGROUND
  Angiotensin-converting enzyme inhibitors (ACEis) improve survival; however, their effect on erythropoiesis remains a matter of debate in this population. Since insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene largely influences serum ACE activity, its effect on erythropoiesis is also anticipated.
  
  
  METHODS
  In this multicentre, cross-sectional study of 660 patients on maintenance haemodialysis, we analysed the effect of ACEi use and ACE gene I/D polymorphism on haemoglobin levels and erythropoietin resistance. Patients were allocated in groups based on genotype and ACEi therapy. We identified 128 matched pairs with I/I and D/D genotypes.
  
  
  RESULTS
  There was no difference in haemoglobin levels between genotype groups. Haemoglobin levels were lower in patients on ACEi therapy in the entire cohort (95.5±12.1 g/l vs 97.4±13.4 g/l, p=0.02) and patients with I/D (95.2±11 g/l vs 98.2±11.9 g/l, p=0.04) and D/D (93.3±13.2 g/l vs 97.4±14.2 g/l, p=0.02) genotypes. In patient pairs treated with ACEi therapy, subjects with D/D genotype had lower Haemoglobin level (93.0±12.8 g/l vs 98.2±11.9 g/l, p=0.006) and higher erythropoietin resistance index (ERI) (199.1 vs 175.0, p=0.046) than individuals with I/I genotype.
  
  
  CONCLUSIONS
  These results indicate that ACEi therapy may increase erythropoietin resistance and worsen erythropoiesis in haemodialysis patients with the D allele.
authors.affiliation: School for Ph.D. Candidates of Aesculap Academy, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kiss
authors.affiliation: B. Braun Avitum Hungary CPLC Dialysis Network, Hungary Department of Nephrology-Hypertension, St Imre University Teaching Hospital, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Ambrus
authors.affiliation: B. Braun Avitum Hungary CPLC Dialysis Network, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Kulcsár
authors.affiliation: B. Braun Avitum Hungary CPLC Dialysis Network, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Szegedi
authors.affiliation: School for Ph.D. Candidates of Aesculap Academy, Hungary Division Section of Geriatrics, 2nd Department of Internal Medicine, Semmelweis University, Hungary ikiss@enternet.hu.
authors.forename: István
authors.initials: I
authors.lastname: Kiss
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D003710:Demography; D004920:Erythropoiesis / Q000187:drug effects* / Q000235:genetics; D004921:Erythropoietin / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D006435:Renal Dialysis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: Angiotensin-converting enzyme; erythropoietin resistance; haemodialysis; haemoglobin; recombinant human erythropoietin