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.

Renal function and genetic polymorphisms in pediatric heart transplant recipients

“…For each GP, models without and with adjustment for recipient sex, race, and age at transplant were created to estimate the effect of the level of exposure for each variant allele (absent, heterozygous, homozygous) on longitudinal eGFR values and time to renal dysfunction after HTx. In addition to assessments based on the ‘allelic content’ of the 19 GPs, we also tested pre-specified genotypes and haplotypes that have been reported to be associated with renal disease [19–20, 25–27] for association with post-transplant renal dysfunction. The genotypes and haplotypes are: IL1-RN allele 2 homozygote, TGFβ1 high producer (TGFβ1 codon 10/25 alleles TC/GG, TT/GG), high IL6/low IL4 producers (IL6/IL4 -590C>T alleles GG/CC), and high TNFα/low IL6/low IL4 producers (TNFα/IL6/IL4 -590C>T alleles AA/CC/CC, AA/CG/CC, GA/CC/CC, GA/CG/CC).…”