Effect of Pravastatin on Total Kidney Volume, Left Ventricular Mass Index, and Microalbuminuria in Pediatric Autosomal Dominant Polycystic Kidney Disease
Effect of Pravastatin on Total Kidney Volume, Left Ventricular Mass Index, and Microalbuminuria in Pediatric Autosomal Dominant Polycystic Kidney Disease
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DOI：
10.2215/cjn.08350813
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发表时间：
2014-05-07
影响因子：
9.8
通讯作者：
Schrier, Robert W.
中科院分区：
文献类型：
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作者：
Cadnapaphornchai, Melissa A.;George, Diana M.;Schrier, Robert W.
背景与目的常染色体显性遗传性多囊肾病（autosomaldominantpolycystickiddisease，ADPKD）中，进行性肾囊肿形成常导致终末期肾病（ESRD）.由于ADPKD的重要表现可能在儿童时期就很明显，因此早期干预可能对长期结果产生最大影响。已知他汀类药物可减缓ADPKD动物模型中的进展性肾病。这项随机双盲安慰剂对照III期临床试验于2007年至2012年进行，旨在评估普伐他汀对患有ADPKD的儿童和年轻成人的身高校正的总肾脏体积（HtTKV）和左心室质量指数（LVMI）（通过磁共振成像（MRI）和尿微量白蛋白排泄（UAE））的影响。110名患有ADPKD且肾功能正常的儿童参与者接受赖诺普利治疗，他们随机接受普伐他汀或安慰剂治疗3年，并在0，18和36个月进行评估。主要结果变量是20%的变化，HtTKV，LVMI，或UAE在研究period. ResultsNinete-one参与者完成了3年的研究（83%）。接受普伐他汀的受试者达到主要终点的人数少于接受安慰剂的受试者（69% vs 88%; P=0.03）。这主要是由于达到HtTKV增加的比例较低（46% vs 68%; P=0.03），在LVMI（25% vs 38%; P=0.18）和UAE（47% vs 39%; P=0.50）研究组之间观察到相似的结果。经年龄、性别和高血压状态调整后的HtTKV在3年内的百分比变化在普伐他汀组显著降低（23%3%vs 31%+/- 3%，P=0.02）。这些发现支持普伐他汀在这种情况下的早期干预作用。
Background and objectivesIn autosomal dominant polycystic kidney disease (ADPKD), progressive kidney cyst formation commonly leads to ESRD. Because important manifestations of ADPKD may be evident in childhood, early intervention may have the largest effect on long-term outcome. Statins are known to slow progressive nephropathy in animal models of ADPKD. This randomized double-blind placebo-controlled phase III clinical trial was conducted from 2007 to 2012 to assess the effect of pravastatin on height-corrected total kidney volume (HtTKV) and left ventricular mass index (LVMI) by magnetic resonance imaging (MRI) and urine microalbumin excretion (UAE) in children and young adults with ADPKD.Designs, setting, participants, & measurements There were 110 pediatric participants with ADPKD and normal kidney function receiving lisinopril who were randomized to treatment with pravastatin or placebo for a 3-year period with evaluation at 0, 18, and 36 months. The primary outcome variable was a 20% change in HtTKV, LVMI, or UAE over the study period.ResultsNinety-one participants completed the 3-year study (83%). Fewer participants receiving pravastatin achieved the primary endpoint compared with participants receiving placebo (69% versus 88%; P=0.03). This was due primarily to a lower proportion reaching the increase in HtTKV (46% versus 68%; P=0.03), with similar findings observed between study groups for LVMI (25% versus 38%; P=0.18) and UAE (47% versus 39%; P=0.50). The percent change in HtTKV adjusted for age, sex, and hypertension status over the 3-year period was significantly decreased with pravastatin (23%3% versus 31%+/- 3%; P=0.02).ConclusionsPravastatin is an effective agent to slow progression of structural kidney disease in children and young adults with ADPKD. These findings support a role for early intervention with pravastatin in this condition.