Effect of angiotensin-converting enzyme gene insertion/deletion polymorphism and angiotensin-converting enzyme inhibition on erythropoiesis in patients on haemodialysis

J Renin Angiotensin Aldosterone Syst. 2015 Dec;16(4):1021-7. doi: 10.1177/1470320314535276. Epub 2014 Jul 7.

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.

Method: 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.

Result: 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.

Conclusion: These results indicate that ACEi therapy may increase erythropoietin resistance and worsen erythropoiesis in haemodialysis patients with the D allele.

Keywords: Angiotensin-converting enzyme; erythropoietin resistance; haemodialysis; haemoglobin; recombinant human erythropoietin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Demography
  • Erythropoiesis / drug effects*
  • Erythropoiesis / genetics
  • Erythropoietin / pharmacology
  • Hemoglobins / metabolism
  • Humans
  • INDEL Mutation / genetics*
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic*
  • Recombinant Proteins / metabolism
  • Renal Dialysis*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Hemoglobins
  • Recombinant Proteins
  • Erythropoietin
  • ACE protein, human
  • Peptidyl-Dipeptidase A