title: Donor and recipient ACE I/D genotype are associated with loss of renal function in children following renal transplantation.
abstract: Genetic polymorphisms of the RAS correlate with allograft function. We therefore analyzed common RAS polymorphisms in kidney donors and in children following RTx to determine the relationship between genotype and decline in GFR, blood pressure, and LVM. A total of 107 children who underwent RTx were included: 70 male, 37 female, mean age 8.8±4.9 yr, mean follow up 5.4 yr. The following RAS polymorphisms were studied in all 107 recipients, 48 donors, and 120 healthy controls: Renin (Renin Mbol 18G/A), ACE I/D; angiotensinogen (AGT M235T), and angiotensin II receptor type-1 (AT1R A1166C). Only patients homozygous for the ACE D allele had a significantly steeper decline in GFR compared with homozygous carriers of the ACE I allele (slope DD: -4.3±0.8 vs. II: -1.3±1.1 mL/min/1.73 m2 per yr; p=0.035). In four cases, a DD recipient received a kidney from a DD donor, and these patients showed a more pronounced decline in GFR (-5.2±0.5 mL/min/1.73 m2 per yr; p=0.002). MABP was not different before vs. after RTx and was independent of ACE I/D genotype. LVMI increased significantly in the majority of patients (36.6±13.9 g/m2.7 six months before RTx vs. 46.4±15.3 g/m2.7 12 months after RTx, p=0.015). However, this difference disappeared after stratification by ACE I/D genotype. The ACE DD genotype is a potential marker for identifying patients at high risk of poor allograft outcome.
authors.affiliation: University of Duisburg-Essen, Children's Hospital, Pediatrics II, Essen, Germany. rainer.buescher@uk-essen.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Büscher
authors.forename: Dominik
authors.initials: D
authors.lastname: Nagel
authors.forename: Ilja
authors.initials: I
authors.lastname: Finkelberg
authors.forename: Anja K
authors.initials: AK
authors.lastname: Büscher
authors.forename: Anne-Margret
authors.initials: AM
authors.lastname: Wingen
authors.forename: Birgitta
authors.initials: B
authors.lastname: Kranz
authors.forename: Udo
authors.initials: U
authors.lastname: Vester
authors.forename: Peter F
authors.initials: PF
authors.lastname: Hoyer
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D011905:Genes, ras / Q000235:genetics*; D005819:Genetic Markers / Q000502:physiology; D005838:Genotype; D005858:Germany; D006084:Graft Rejection / Q000235:genetics; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods; D016014:Linear Models; D019520:Living Donors; D008297:Male; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000175:diagnosis / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D044140:Receptor, Angiotensin, Type 1