Woo Keng Thye, Lau Yeow Kok, Zhao Yi, Liu Fang E, Tan Hwee Boon, Tan Eng Keng, Stephanie Fook Chong, Chan Choong Meng, Wong Kok Seng
Department of Renal Medicine, Singapore General Hospital, Singapore.
Cell Mol Immunol. 2007 Jun;4(3):227-32.
Various studies have shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (ID) polymorphism may play a role in the progression to end stage renal failure (ESRF) in patients with IgA nephritis (IgAN). In this randomized controlled trial, patients were followed up for 5 years to determine their long-term renal outcome to ACEI/ATRA therapy and to ascertain if their ACE gene profile could play a role in determining their response to therapy. Seventy-five patients with IgAN were enlisted. Thirty-seven were on ACEI/ATRA therapy for 62+/-5 months and thirty-eight were untreated and served as controls. All patients had their ACE gene ID polymorphism genotyped. Compared to controls, treated patients had lower serum creatinine (p < 0.001), lower proteinuria (p < 0.002) and fewer numbers progressing to ESRF (p < 0.002). Among patients with genotype II, there were less ESRF in the treatment group when compared to the untreated control group (p < 0.02). The advantage of therapy was not seen in patients with ID or DD genotypes. ACEI/ATRA therapy was found to be effective in retarding disease progression in IgAN with years to ESRF significantly extended in patients at all levels of renal function, including patients whose outcome were ESRF. Genotyping showed better response to therapy only for those with genotype II. The common mechanism is probably through lower levels of ACE, glomerular pressure and proteinuria resulting in reduced renal damage and retardation of progression to ESRF.
多项研究表明，血管紧张素转换酶（ACE）基因插入/缺失（ID）多态性可能在IgA肾病（IgAN）患者进展至终末期肾衰竭（ESRF）的过程中发挥作用。在这项随机对照试验中，对患者进行了5年的随访，以确定他们对ACEI/ATRA治疗的长期肾脏结局，并确定其ACE基因谱是否在决定其对治疗的反应中起作用。招募了75例IgAN患者。37例接受ACEI/ATRA治疗62±5个月，38例未接受治疗作为对照。所有患者均对ACE基因ID多态性进行了基因分型。与对照组相比，接受治疗的患者血清肌酐水平较低（p<0.001），蛋白尿较少（p<0.002），进展至ESRF的人数较少（p<0.002）。在基因型为II的患者中，治疗组的ESRF患者少于未治疗的对照组（p<0.02）。在ID或DD基因型患者中未观察到治疗的优势。发现ACEI/ATRA治疗可有效延缓IgAN的疾病进展，所有肾功能水平的患者进展至ESRF的时间均显著延长，包括那些结局为ESRF的患者。基因分型显示仅基因型为II的患者对治疗反应更好。常见机制可能是通过降低ACE水平、肾小球压力和蛋白尿，从而减少肾脏损伤并延缓进展至ESRF。
