Narasimhan Kannan Laksmi, Khullar Madhu, Kaur Balpinder
Department of Pediatric Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh UT, 160012, India.
J Pediatr Urol. 2007 Aug;3(4):287-90. doi: 10.1016/j.jpurol.2006.10.011. Epub 2007 Jan 31.
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).
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).
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.
The presence of D allele is associated with progression of renal scarring and reduced GFR in PUV patients.
探讨血管紧张素转换酶（ACE）基因插入/缺失（I/D）多态性及其他危险因素与后尿道瓣膜（PUV）患者肾瘢痕形成的关系。
1997年至2004年，对印度西北部连续40例PUV患者进行治疗。根据二巯基琥珀酸扫描结果，将患者分为1组（无肾瘢痕，n = 12）和2组（有肾瘢痕，n = 28）。通过聚合酶链反应测定PUV患者及无关健康对照者（n = 100）的ACE I/D多态性。
就诊时平均年龄为23.7±37.2个月，平均随访时间为4.8±1.5年。1组（无瘢痕）和2组（有瘢痕）术前平均血清肌酐水平分别为1.1±1.6mg/dl和1.7±1.6mg/dl。治疗1年后，1组和2组的血清肌酐水平分别降至0.6±0.1mg/dl和0.8±0.3mg/dl。PUV患儿的ACE基因型分布与对照组无差异。2组患者中D等位基因的发生率显著更高（p = 0.04）。多因素逻辑回归分析显示，D等位基因对肾瘢痕形成有显著影响，使风险增加4.6倍（优势比4.6，95%置信区间1.03 - 20.38，p = 0.04）。观察到肾瘢痕形成的发生与突破性尿路感染的存在（优势比 = 7.5，95%置信区间1.60 - 35.07，p = 0.006）以及随访时的血清肌酐（优势比 = 0.6，95%置信区间0.47 - 0.81，p = 0.03）之间存在高度显著的相关性。II基因型和ID/DD基因型患者治疗1年后（p = 0.006）和随访时（p = 0.027）的肾小球滤过率（GFR）平均值有显著差异。13例患者出现高血压，9例患者出现蛋白尿，II/ID/DD基因型患者之间无显著差异。
D等位基因的存在与PUV患者肾瘢痕进展及GFR降低有关。
