Mineralocorticoid Antagonism and Vascular Function in Early Autosomal Dominant Polycystic Kidney Disease: A Randomized Controlled Trial.
Mineralocorticoid Antagonism and Vascular Function in Early Autosomal Dominant Polycystic Kidney Disease: A Randomized Controlled Trial.
复制标题
早期常染色体显性多囊肾病中的盐皮质激素拮抗作用和血管功能：随机对照试验。
DOI：
10.1053/j.ajkd.2018.12.037
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Chonchol,Michel
中科院分区：
文献类型：
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作者：
Nowak,KristenL;Gitomer,Berenice;Farmer-Bailey,Heather;Wang,Wei;Malaczewski,Mikaela;Klawitter,Jelena;You,Zhiying;George,Diana;Patel,Nayana;Jovanovich,Anna;Chonchol,Michel
Rationale & ObjectiveVascular dysfunction, characterized by impaired vascular endothelial function and increased large-elastic artery stiffness, is evident early in autosomal dominant polycystic kidney disease (ADPKD) and is an important predictor of cardiovascular events and mortality. Aldosterone excess has been implicated in the development of endothelial dysfunction and arterial stiffness, in part by causing increased oxidative stress and inflammation. We hypothesized that aldosterone antagonism would reduce vascular dysfunction in patients with early-stage ADPKD.Study DesignProspective, randomized, controlled, double-blind, clinical trial.Setting & Participants61 adults aged 20 to 55 years with ADPKD, estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2, and receiving a renin-angiotensin-aldosterone system inhibitor.InterventionSpironolactone (maximum dose, 50 mg/d) or placebo for 24 weeks.OutcomesChange in brachial artery flow-mediated dilation (FMDBA) was the primary end point and change in carotid-femoral pulse-wave velocity (CFPWV) was the secondary end point.Results60 participants completed the trial. Participants had a mean age of 34 ± 10 (SD) years, 54% were women, and 84% were non-Hispanic white. Spironolactone did not change FMDBA(8.0% ± 5.5% and 7.8% ± 4.3% at baseline and 24 weeks, respectively, vs corresponding values in the placebo group of 8.4% ± 6.2% and 8.0% ± 4.6%;P= 0.9 for comparison of change between groups) or CFPWV (640 ± 127 and 603 ± 101 cm/s at baseline and 24 weeks, respectively, vs corresponding values in the placebo group of 659 ± 138 and 658 ± 131 cm/s;P= 0.1). Brachial systolic blood pressure was reduced with spironolactone (median change, −6 [IQR, −15, 1] vs −2 [IQR, −7, 10] mm Hg in the placebo group;P= 0.04). Spironolactone did not change the majority of circulating and/or endothelial cell markers of oxidative stress/inflammation and did not change vascular oxidative stress.LimitationsLow level of baseline vascular dysfunction; lack of aldosterone measurements.Conclusions24 weeks of aldosterone antagonism reduced systolic blood pressure without changing vascular function in patients with early-stage ADPKD.FundingNIDDK, NIH National Center for Advancing Translational Sciences, and the Zell Family Foundation.Trial RegistrationRegistered at ClinicalTrials.gov with study number NCT01853553.
