title: Impact of genetic polymorphisms of the renin-angiotensin system and of non-genetic factors on kidney transplant function--a single-center experience.
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.
authors.affiliation: Klinik fuer Nephrologie, Heinrich-Heine Universitaet Duesseldorf, Dusseldorf, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Siekierka-Harreis
authors.forename: Nicola
authors.initials: N
authors.lastname: Kuhr
authors.forename: Rainhart
authors.initials: R
authors.lastname: Willers
authors.forename: Katrin
authors.initials: K
authors.lastname: Ivens
authors.forename: B
authors.initials: B
authors.lastname: Grabensee
authors.forename: Adrian
authors.initials: A
authors.lastname: Mondry
authors.forename: Marie C S
authors.initials: MC
authors.lastname: Loh
authors.forename: Lars Christian
authors.initials: LC
authors.lastname: Rump
authors.forename: Cornelia
authors.initials: C
authors.lastname: Blume
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A