Angiotensin-converting enzyme gene polymorphism in North-west Indian children with posterior urethral valves

Abstract Purpose To investigate the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and other risk factors with renal scarring in patients with posterior urethral valves (PUV). Materials and methods Forty consecutive patients from North-west India were treated for PUV in 1997–2004. The patients were divided into group 1 (no renal scarring, n = 12) and group 2 (renal scars present, n = 28) based on dimercato-succinic acid scans. ACE I/D polymorphism was determined by polymerase chain reaction in PUV patients and unrelated healthy controls ( n = 100). Results Mean age at presentation was 23.7 ± 37.2 months and mean follow up was 4.8 ± 1.5 years. Preoperative mean serum creatinine levels for group 1 (non-scarred) and group 2 (scarred) were 1.1 ± 1.6 mg/dl and 1.7 ± 1.6 mg/dl, respectively. One year after treatment, the serum creatinine levels had decreased to 0.6 ± 0.1 mg/dl and 0.8 ± 0.3 mg/dl in group 1 and group 2, respectively. ACE genotype distribution in children with PUV was no different from that of controls. The occurrence of D allele was significantly ( p = 0.04) higher in patients of group 2. Multivariate logistic regression analysis showed that D allele had a significant impact on renal scar formation, introducing a 4.6-fold risk (odds ratio 4.6, 95% confidence interval 1.03–20.38, p = 0.04). A highly significant correlation between the occurrence of renal scarring and presence of breakthrough urinary tract infection (odds ratio = 7.5, 95% confidence interval 1.60–35.07, p = 0.006) and serum creatinine at follow up (odds ratio = 0.6, 95% confidence interval 0.47–0.81, p = 0.03) was observed. The mean values for glomerular filtration rate (GFR) after 1 year of treatment ( p = 0.006) and at follow up ( p = 0.027) were significantly different between the patients with II genotype and ID/DD genotype. Hypertension was observed in 13 patients and proteinuria in nine patients with no significant difference between the patients having II/I D/DD genotypes. Conclusion The presence of D allele is associated with progression of renal scarring and reduced GFR in PUV patients.