Recipient ras gene variants and renal allograft function1

BACKGROUND: Genetic variants of the renin-angiotensin system (RAS) have been implicated in the progression of native kidney diseases. A decreased long-term renal allograft function has also been associated with increased activity of RAS, which may be genetically determined. METHODS: The effect of the angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin type 1 receptor (AGT1R), and aldosterone synthase (CYP11B2) genotypes on renal function was investigated in 223 first-allograft recipients. Graft function was estimated by yearly determinations of serum creatinine. Genotyping was performed for the M235T-AGT, the I/D-ACE, the A1166C-AGT1R, and the -344T/C-CYP11B2 gene polymorphisms using polymerase chain reaction. RESULTS: The percentage of patients with preserved stable graft function up to 15 years after transplantation was higher when mean blood pressure was <97 mmHg, than when it was >117 mmHg (60 vs. 25% of patients). The CYP11B2 genotype predicted long-term stable graft function with more patients suffering from worsening renal function with the CYP11B2 TT than the CC genotype (P=0.002). There was a weak association between the AGT1R genotype (P=0.037), but not the AGT or ACE genotypes, and a preserved long-term graft function. Cox proportional hazards estimation showed no interactions between the observed effect of CYP11B2 genotype on renal function over time and the number of HLA class I and II matches, other RAS genotypes, graft function, or mean blood pressure at 1 year after transplantation. CONCLUSIONS: The rate of decline in renal allograft function is strongly associated with the CYP11B2 but not AGT, ACE, or AGT1R genotypes. This finding suggests that certain genetic factors related to the RAS are important determinants of long-term renal allograft function.