Impact of ACE I/D gene polymorphism on congenital renal malformations

To investigate the role of the angiotensin converting enzyme (ACE) gene ins ertion/deletion (I/D) polymorphism on prevalence and progression of disease in children with chronic renal failure (CRF), we determined the ACE I/D ge notype in 95 children with CRF due to renal malformations (hypo-/dysplasia, obstructive uropathy, reflux nephropathy; n=59), other congenital or hered itary diseases (n=23), or acquired glomerular disorders (n=13), who had bee n followed prospectively over a 2-year period. CRF progression rate was fol lowed in each individual by linear regression analysis of estimates of glom erular filtration rate (GFR) obtained every 2 months. Actuarial renal 'surv ival' analysis was performed, using a GFR loss of 10 ml/min per 1.73 m(2) a s a cutoff point. The distribution of the ACE genotype did not differ among the disease groups. There was also no difference in ACE genotype distribut ion between the patients and a control group of healthy Caucasian children (n=163), Among the children with renal malformations, the 2-year renal surv ival was significantly lower in those with the DD genotype (61%) than in pa tients with ID or II genotype (89%, P <0.01). In the other disease groups, the ACE I/D genotype was not predictive of CRF progression. In a multivaria te analysis of risk factors, the adverse effect of the DD genotype (risk ra tio 10.2, P <0.05) was independent of and additive to those of arterial hyp ertension (RR 13.2, P <0.001) and gross proteinuria (RR 4.7, P <0.05). We c onclude that the ACE DD genotype is a significant risk factor for children with congenital renal malformations to develop progressive CRE The effect o f the ACE polymorphism in this patient group is independent of hypertension and proteinuria.