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.
Objectives:Aquaporins, a family of transmembrane water channels, are expressed in the kidney and are involved in chronic renal allograft dysfunction. A novel gain of function promotor polymorphism in the Aquaporin 5 gene (AQP5‐1364 A/C) has recently been demonstrated to alter AQP5 expression and might therefore contribute to water and salt homeostasis. We investigated whether the AQP5‐1364 A/C SNP is associated with loss of glomerular filtration rate (GFR, ml/min/1.73m2) and blood pressure in children following renal transplantation (RTx).Methods and Results:91 children (60 male, 31 female, mean age at RTx 9.6 years, mean follow up time 5.4 years) were included. The slope of GFR was determined by linear regression analysis. Allelic frequencies were not significantly different from healthy controls. However, homozygous C‐allele carriers were not detected in our study group. Loss of GFR and blood pressure were not different between the groups (AQP5‐1364 A/C: slope AA −0.02±0.17 vs. AC −0.22±0.17, p=0.454.Conclusion:The AQP5‐1364 A/C promotor polymorphism is not associated with the loss of renal function and blood pressure in children following RTx.
Preservation of a stable allograft function in children following renal transplantation (RTx) depends on various factors including blood pressure and genetic variability. Due to their impact on blood pressure regulation we have studied polymorphisms of the renin‐angiotensin‐aldosterone system and TGFβ1 in 91 children following RTx and associated genotypes with loss of glomerular filtration rate (GFR, ml/min/1.73m2) and blood pressure (mean observation time 5.4 years). We studied the Renin G1883A, ACE I/D, Angiotensinogen (AGT) Met235Thr and Angiotensin II receptor type‐1 (AT1R) A1166C polymorphism as well as TGFβ1 (TGFB1) C509T and Leu10Pro. Allelic frequencies were not significantly different from healthy controls. Genotypes of Renin, AGT, AT1R and TGFB1 showed no significant association with the slope of GFR but ACE DD‐carriers had a significantly steeper decline of GFR and a higher systolic and diastolic blood pressure before RTx when compared to ACE II‐carriers (slope DD‐4.289±0.832 vs. II‐1.333±1.107, p=0.035). We conclude that the ACE DD‐genotype may contribute to a faster, non immunological renal allograft failure.
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