Khurana Mona, Silverstein Douglas M
Center for Drug Evaluation and Research Office of New Drugs Division of Nonprescription Regulation Development, United States Food and Drug Administration, Silver Spring, MD, USA.
Center for Devices and Radiological Health, Division of Reproductive, Gastro-Renal and Urological Devices, Renal Devices Branch, United States Food and Drug Administration, 10903 New Hampshire Avenue Building 66-G252, Silver Spring, MD, 20993, USA.
Pediatr Nephrol. 2015 Dec;30(12):2073-84. doi: 10.1007/s00467-015-3075-9. Epub 2015 Mar 24.
Lipids are essential components of cell membranes, contributing to cell fuel, myelin formation, subcellular organelle function, and steroid hormone synthesis. Children with chronic kidney disease (CKD) and end-stage renal disease (ESRD) exhibit various co-morbidities, including dyslipidemia. The prevalence of dyslipidemias in children with CKD and ESRD is high, being present in 39-65% of patients. Elevated lipid levels in children without renal disease are a risk factor for cardiovascular disease (CVD), while the risk for CVD in pediatric CKD/ESRD is unclear. The pathogenesis of dyslipidemia in CKD features various factors, including increased levels of triglycerides, triglyceride-rich lipoproteins, apolipoprotein C3 (ApoC-III), decreased levels of cholesterylester transfer protein and high-density lipoproteins, and aberrations in serum very low-density and intermediate-density lipoproteins. If initial risk assessment indicates that a child with advanced CKD has 2 or more co-morbidities for CVD, first-line treatment should consist of non-pharmacologic management such as therapeutic lifestyle changes and dietary counseling. Pharmacologic treatment of dyslipidemia may reduce the incidence of CVD in children with CKD/ESRD, but randomized trials are lacking. Statins are the only class of lipid-lowering drugs currently approved by the U.S. Food and Drug Administration (FDA) for use in the pediatric population. FDA-approved pediatric labeling for these drugs is based on results from placebo-controlled trial results, showing 30-50% reductions in baseline low-density lipoprotein cholesterol. Although statins are generally well tolerated in adults, a spectrum of adverse events has been reported with their use in both the clinical trial and post-marketing settings.
脂质是细胞膜的重要组成部分,对细胞供能、髓鞘形成、亚细胞器功能及类固醇激素合成均有作用。患有慢性肾脏病(CKD)和终末期肾病(ESRD)的儿童存在多种合并症,包括血脂异常。CKD和ESRD患儿血脂异常的患病率很高,39%至65%的患者存在该问题。无肾脏疾病儿童的血脂水平升高是心血管疾病(CVD)的危险因素,而儿科CKD/ESRD患者发生CVD的风险尚不清楚。CKD患者血脂异常的发病机制涉及多种因素,包括甘油三酯、富含甘油三酯的脂蛋白、载脂蛋白C3(ApoC-III)水平升高,胆固醇酯转运蛋白和高密度脂蛋白水平降低,以及血清极低密度脂蛋白和中间密度脂蛋白异常。如果初始风险评估表明患有晚期CKD的儿童有2种或更多CVD合并症,一线治疗应包括非药物管理,如治疗性生活方式改变和饮食咨询。对CKD/ESRD患儿进行血脂异常的药物治疗可能会降低CVD的发生率,但缺乏随机试验。他汀类药物是目前美国食品药品监督管理局(FDA)批准用于儿科人群的唯一一类降脂药物。FDA批准的这些药物的儿科标签基于安慰剂对照试验结果,显示基线低密度脂蛋白胆固醇降低30%至50%。尽管他汀类药物在成人中通常耐受性良好,但在临床试验和上市后环境中均有使用这些药物后出现一系列不良事件的报告。