Department of Biophysics, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
Biol Chem. 2013 Mar;394(3):369-77. doi: 10.1515/hsz-2012-0314.
There is a consensus in the scientific literature that supports the importance of the kallikrein kinin and renin angiotensin systems in renal physiology, but few studies have investigated their importance after renal transplantation. The aim of this study was to investigate the clinical effects of the insertion/deletion polymorphism in the angiotensin I-converting enzyme (ACE) gene and the +9/-9 polymorphism in the kinin B2 receptor (B2R) gene in kidney-transplanted patients (n=215 ACE, n=203 B2R) compared with 443 healthy individuals. Demographic results showed that there is a higher frequency of the D allele (high plasma ACE activity) and +9 allele (lower B2R expression) in transplant patients compared with control individuals. We also observed a higher frequency of these alleles in patients who had an elevated level of plasma creatinine. At day 7 post-transplantation, we found a higher prevalence of individuals with the DD genotype with elevated plasma creatinine level. Furthermore, individuals with the DD genotype had a higher chronic allograft dysfunction and graft loss compared with the II patient genotype, which showed no loss of graft. Taken together, our data suggest that the DD genotype is an indicator of an unfavorable prognosis following renal transplantation and could be related to kinin modulation.
科学文献中有共识支持激肽释放酶-激肽系统和肾素-血管紧张素系统在肾脏生理学中的重要性,但很少有研究调查它们在肾移植后的重要性。本研究旨在调查肾移植患者(ACE 基因插入/缺失多态性 n=215,B2R 基因+9/-9 多态性 n=203)与 443 名健康个体相比,血管紧张素转换酶(ACE)基因和缓激肽 B2 受体(B2R)基因中的插入/缺失多态性的临床影响。人口统计学结果表明,与对照组相比,移植患者的 D 等位基因(高血浆 ACE 活性)和+9 等位基因(B2R 表达降低)的频率更高。我们还观察到这些等位基因在血浆肌酐水平升高的患者中频率更高。在移植后 7 天,我们发现血浆肌酐水平升高的患者中 DD 基因型的患病率更高。此外,与 II 型患者基因型相比,DD 基因型的个体发生慢性移植物功能障碍和移植物丢失的风险更高,而 II 型患者基因型则没有发生移植物丢失。综上所述,我们的数据表明 DD 基因型是肾移植后预后不良的指标,可能与激肽调节有关。