Brock J W, Adams M, Hunley T, Wada A, Trusler L, Kon V
Department of Pediatric Urology Surgery, Vanderbilt Children's Hospital, Nashville, Tennessee, USA.
J Urol. 1997 Sep;158(3 Pt 2):1308-11. doi: 10.1097/00005392-199709000-00171.
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.
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.
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 parenchymal 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.
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.
实验研究和人体研究均已证实肾素 - 血管紧张素系统在肾功能进行性恶化中起重要作用。最近，肾素 - 血管紧张素系统各组分的基因多态性已与多种心血管疾病相关，特别是血管紧张素转换酶基因的变异，其中涉及一个287 bp片段的插入（I）或缺失（D）。D变异型已与心肌梗死和心脏肥大相关。
为评估这种基因变异是否与肾脏疾病的不良预后相关，我们评估了70例先天性泌尿系统异常的儿童，因为即使在早期进行矫正干预后，仍有相当数量的患儿会出现进行性肾功能恶化。通过是否存在实质损伤的影像学证据和血清肌酐来评估肾功能恶化情况。
在无肾脏实质损伤影像学证据的患者中，血管紧张素转换酶基因型II、ID和DD的分布分别为24%、67%和9%。相比之下，在有实质损伤证据的患者中观察到血管紧张素转换酶基因型分布有显著差异，即II、ID和DD分别为10%、49%和41%（p < 0.05，卡方值5.0）。前一组的平均血清肌酐加或减标准误正常，为0.6±0.1mg./dl，而有瘢痕形成的患者血清肌酐升高，为1.1±0.1mg./dl，正如预期。在DD基因型的患者中，观察到实质损伤的发生率极高，即在所有22例该基因型患者中，有20例（91%）存在实质损伤。
综合考虑，这些研究表明，有肾脏实质损伤证据的先天性泌尿系统异常患者与无此类损伤的患者相比，血管紧张素转换酶基因多态性的分布存在差异。鉴于这种基因变异会激活肾素 - 血管紧张素系统，且这种激活在肾脏中可能尤为强烈，我们提出在这种情况下，个体的基因型独立于其他因素会改变实质损失的可能性。
