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±1.6mg/dl and 1.7±1.6mg/dl, respectively. One year after treatment, the serum creatinine levels had decreased to 0.6±0.1mg/dl and 0.8±0.3mg/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.

Keywords: Posterior urethral valves, Angiotensin-converting enzyme, Polymorphism, Scarring