Department of Paediatric Nephrology and Wellcome Trust Children's Clinical Research Facility, The University of Manchester, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Manchester, UK.
Kidney Int. 2012 Oct;82(7):819-26. doi: 10.1038/ki.2012.210. Epub 2012 Jun 27.
Angiotensin-converting enzyme inhibitors and angiotensin II type I receptor blockers delay progression of chronic kidney disease and have antiproteinuric effects beyond their effects on blood pressure. They are routinely used in adults; however, their efficacy and safety in children, in whom the causes of chronic kidney disease are significantly different relative to adults, is uncertain. Here we assessed an open-label extension of a previous 3-month blinded trial, in which the efficacy and tolerability of losartan was compared to placebo or amlodipine in 306 normotensive and hypertensive children with proteinuria. In this study, 268 children were re-randomized to losartan or enalapril and followed until 100 patients completed 3 years of follow-up for proteinuria and renal function. The least squares percent mean reduction from baseline in the urinary protein/creatinine ratio was 30.01% for losartan and 40.45% for enalapril. The least squares mean change from baseline in eGFR was 3.3 ml/min per 1.73 m2 for losartan and 7.0 ml/min per 1.73 m2 for enalapril. The incidence of specific adverse events such as hyperkalemia and renal dysfunction was low and similar in both groups. Both were generally well tolerated and, overall, fewer drug-related adverse events occurred with losartan than with enalapril. Thus, in children with proteinuria, losartan and enalapril significantly reduced proteinuria without any appreciable changes in eGFR, effects that were maintained throughout the study. Both losartan and enalapril were generally well tolerated.
血管紧张素转换酶抑制剂和血管紧张素 II 型 1 型受体阻滞剂可延缓慢性肾脏病的进展,除了降低血压外,还有减少蛋白尿的作用。它们在成人中常规使用;然而,在儿童中,其疗效和安全性尚不确定,因为儿童慢性肾脏病的病因与成人有显著不同。在这里,我们评估了一项先前为期 3 个月的双盲试验的开放标签扩展研究,该研究比较了氯沙坦与安慰剂或氨氯地平在 306 例蛋白尿的正常血压和高血压儿童中的疗效和耐受性。在这项研究中,268 例儿童重新随机分配至氯沙坦或依那普利,并随访至 100 例患者完成蛋白尿和肾功能 3 年的随访。与基线相比,氯沙坦组尿蛋白/肌酐比值的最小平方均数降低了 30.01%,依那普利组降低了 40.45%。与基线相比,氯沙坦组 eGFR 的最小平方均值变化为 3.3 ml/min/1.73 m2,依那普利组为 7.0 ml/min/1.73 m2。高钾血症和肾功能不全等特定不良事件的发生率较低,且两组相似。两种药物总体上均耐受良好,与依那普利相比,氯沙坦发生药物相关不良事件的发生率较低。因此,在蛋白尿儿童中,氯沙坦和依那普利可显著减少蛋白尿,而 eGFR 无明显变化,这一效果在整个研究期间得以维持。氯沙坦和依那普利总体上均耐受良好。