Department of Paediatric Nephrology and Wellcome Trust Children's Clinical Research Facility, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, The University of Manchester, Manchester, UK.
Pediatr Nephrol. 2013 May;28(5):737-43. doi: 10.1007/s00467-012-2372-9. Epub 2012 Dec 4.
A previous subgroup analysis of a 12-week, double-blind study demonstrated that losartan significantly lowered proteinuria versus placebo and amlodipine and was well tolerated in children (1-17 years old) with proteinuria secondary to Alport syndrome. The present subgroup analysis of the open-label, extension phase of this study assessed the long-term efficacy and tolerability of losartan versus enalapril.
Patients who had completed the double-blind study were re-randomized to losartan or enalapril and followed for proteinuria and renal function for up to 3 years.
Twenty-seven patients with Alport syndrome were randomized to losartan (0.44-2.23 mg/kg/day; n = 15) or enalapril (0.07-0.72 mg/kg/day; n = 12). The least-squares (LS) mean percent change from week 12 in urinary protein to creatinine ratio (UPr/Cr was +1.1 % in the losartan group versus a further 13.9 % reduction in the enalapril group (GMR [95 % CI] = 1.2 [0.7, 2.0]); the LS mean change from week 12 in estimated glomerular filtration rate (eGFR) was -6.4 ml/min/1.73 m(2) in the losartan group versus -9.1 ml/min/1.73 m(2) in the enalapril group. The adverse event incidence was low and comparable in both treatment groups.
In children with proteinuria secondary to Alport syndrome, losartan maintained proteinuria reduction, and enalapril produced a further proteinuria reduction over the 3-year study period. Both agents were generally well tolerated.
一项为期 12 周的双盲研究的亚组分析表明,氯沙坦可显著降低蛋白尿,优于安慰剂和氨氯地平,并且在伴有蛋白尿的 Alport 综合征患儿(1-17 岁)中耐受性良好。本研究为该双盲研究开放标签扩展阶段的亚组分析,评估了氯沙坦与依那普利的长期疗效和耐受性。
完成双盲研究的患者被重新随机分为氯沙坦或依那普利组,并随访蛋白尿和肾功能,最长达 3 年。
27 例 Alport 综合征患者被随机分为氯沙坦(0.44-2.23mg/kg/天;n=15)或依那普利(0.07-0.72mg/kg/天;n=12)组。从第 12 周开始,尿蛋白与肌酐比值(UPr/Cr)的最小二乘(LS)均值变化,氯沙坦组增加 1.1%,依那普利组进一步减少 13.9%(GMR [95%CI]为 1.2 [0.7, 2.0]);LS 均值估计肾小球滤过率(eGFR)从第 12 周开始变化,氯沙坦组减少 6.4ml/min/1.73m(2),依那普利组减少 9.1ml/min/1.73m(2)。两组不良事件发生率均较低且相当。
在伴有蛋白尿的 Alport 综合征患儿中,氯沙坦可维持蛋白尿减少,依那普利在 3 年研究期间进一步降低蛋白尿。两种药物通常均具有良好的耐受性。