ACE I/D gene polymorphism predicts renal damage in congenital uropathies

We investigated angiotensin converting enzyme gene (ACE IID) polymorphism a s a risk for progressive renal damage in congenital uropathies. The ACE In, genotype was determined in 196 Caucasian patients with congenital uropathi es and 163 individuals with no clinical or sonographic evidence of any urol ogical malformations. The study group included patients with ureteropelvic junction obstruction (n = 49), primary obstructive megaureter (n = 19), pri mary vesicoureteral reflux (VUR) (n = 67), and posterior urethral valves (n = 27). Thirty-four patients were excluded because of additional diseases o r insufficient follow-up. There was no difference in the ACE IID distributi on between children with uropathies and normal controls (II 16%, ID 56%, DD 28% vs. II 26%, ID 50%, DD 24%). Renal lesions were found in 99 of 162 chi ldren by ultrasonography, intravenous pyelography, and nuclear scans. In th ese children there was significant over-representation of the DD genotype ( II 11%, TC, 53%, DD 36%) compared with normals (P < 0.005, X-2 = 14.9) or w ith patients with uropathies but no renal lesions (II 23%, ID 62%, DD 15%, P < 0.005, X-2 = 14.9). Because ACE IID has been linked with progressive de terioration of renal function, we evaluated a subset of patients with initi ally normal kidneys who developed radiographic renal lesions (n = 28). Amon g these patients there was an even greater over-representation of the DD ge notype (II 0%, ID 43%, DD 57%, P < 0.001, X-2 = 22.6) compared with patient s with uropathies but no radiographic lesions. Multivariate analysis reveal ed that the DD genotype is a risk factor for parenchymal destruction, which was independent of time of diagnosis, surgical intervention, or urinary tr act infection. This finding was particularly relevant in patients with WR w ho constituted the majority with initially normal kidneys who developed rad iographic damage (22/28). Indeed, the odds ratio of developing parenchymal damage with VUR was significantly increased if the individual had the DD ge notype (4.2, 95% confidence interval 1.4-13.0). In conclusion the ACE I/D g ene polymorphism is a risk factor for renal parenchymal damage in patients with congenital urological abnormalities and appears particularly relevant in children with VUR, where it is an independent predisposing factor.