Impact of genetic polymorphisms of the renin-angiotensin system and of non-genetic factors on kidney transplant function--a single-center experience

Clin Transplant. 2009 Sep-Oct;23(5):606-15. doi: 10.1111/j.1399-0012.2009.01033.x. Epub 2009 Aug 4.

Abstract

Renin-angiotensin-aldosterone system (RAAS) polymorphisms such as the angiotensinogen-gene-M235T-, the angiotensin-conversion enzyme (ACE)-gene I/D- and the angiotensin-II-type 1-receptor-(AT1R)-A1166C-polymorphism have been implicated in renal insufficiency and hypertension. We studied the association of these RAAS genotypes and non-genetic factors with transplant function and hypertension after renal graft transplantation (NTX). A total of 229 renal graft recipients, transplanted at a single center, were monitored up to 54 months and genotyped using polymerase chain reaction. The prevalence of the genotypes was comparable to a control group of healthy volunteers. Genotype and clinical outcome was analyzed using ANOVA, while the k-nearest neighbor method was used for a pattern recognition analysis of the complete database. Hypertension after NTX was not influenced by the RAAS polymorphisms. The DD-genotype of the ACE-I/D-polymorphism was associated with significantly deteriorated renal transplant function during the months 18 to 30 after transplantation according to ANOVA at p < 0.05, as were non-genetic factors like long hospitalization, poor primary transplant function, and frequent rejections. Pattern recognition identified, the use of cyclosporine (odds ratio of 4.25) and the use of Ang II-receptor-blockers at discharge indicating the need of effective antihypertensive treatment (odds ratio of 3.26) as risk factors for transplant function loss. Altogether, the significant impact of the DD-genotype on the outcome after renal transplantation emphasizes the early identification of RAAS genotypes.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Angiotensinogen / genetics
  • Case-Control Studies
  • Female
  • Genotype
  • Graft Rejection / genetics*
  • Humans
  • Hypertension / etiology
  • Hypertension / genetics*
  • Hypertension / prevention & control
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / surgery
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics
  • Phenotype
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Receptor, Angiotensin, Type 1 / genetics
  • Renin-Angiotensin System / genetics*
  • Risk Factors
  • Survival Rate
  • Treatment Outcome

Substances

  • Receptor, Angiotensin, Type 1
  • Angiotensinogen
  • Peptidyl-Dipeptidase A