Potential risk factors associated with progressive renal damage in childhood urological diseases: The role of angiotensin-converting enzyme gene polymorphism

被引:29
作者
Brock, JW [1 ]
Adams, M [1 ]
Hunley, T [1 ]
Wada, A [1 ]
Trusler, L [1 ]
Kon, V [1 ]
机构
[1] VANDERBILT UNIV, CHILDRENS HOSP, DEPT PEDIAT NEPHROL, NASHVILLE, TN USA
关键词
kidney; renin-angiotensin system; kininase II; chromosomes; human;
D O I
10.1016/S0022-5347(01)64463-X
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Experimental as well as human studies have established an important role for the renin-angiotensin system in the progressive deterioration of renal function. Recently genetic polymorphism in components of the renin-angiotensin system has been associated with several cardiovascular diseases, particularly variations in the angiotensin-converting enzyme gene that involve insertion (I) or deletion (D) of a 287 bp fragment. The D variant has been associated with myocardial infarction and cardiac hypertrophy. Materials and Methods: To assess whether this genetic variant is associated with worse prognosis in renal disorders we evaluated 70 children with congenital urological abnormalities, since a substantial number have progressive renal deterioration even after early corrective intervention Renal deterioration was assessed by the presence or absence of radiographic evidence of parenchymal damage and serum creatinine. Results: Among patients with no radiographic renal parenchymal damage angiotensin-converting enzyme genotype distribution of II, ID and DD was 24, 67 and 9%, respectively. In contrast, a significantly different angiotensin-converting enzyme genotype distribution was observed in patients with evidence of pareachymal damage, that is 10, 49 and 41% for II, ID and DD, respectively (p < 0.05, chi-square 5.0). Mean serum creatinine plus or minus standard error in the former group was normal at 0.6 +/- 0.1 mg./dl., while in those with scarring it was elevated at 1.1 +/- 0.1 mg./dl., as expected. In patients with the DD genotype an overwhelming frequency of parenchymal damage was observed, that is of all 22 with that genotype 20 (91%) had parenchymal damage. Conclusions: Considered together, these studies suggest that there are differences in the distribution of angiotensin-converting enzyme gene polymorphism in patients with congenital urological abnormalities who have evidence of renal parenchymal damage versus those who do not have such damage. Given that this genetic variation activates the renin-angiotensin system and this activation may be particularly robust in the kidney, we propose that the genotype of an individual independent of other factors modifies the likelihood of parenchymal loss in this setting.
引用
收藏
页码:1308 / 1311
页数:4
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