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American Journal of Kidney Diseases

Mineralocorticoid Antagonism and Vascular Function in Early Autosomal Dominant Polycystic Kidney Disease: A Randomized Controlled Trial

Published:February 22, 2019DOI:https://doi.org/10.1053/j.ajkd.2018.12.037

      Rationale & Objective

      Vascular 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 Design

      Prospective, randomized, controlled, double-blind, clinical trial.

      Setting & Participants

      61 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.

      Intervention

      Spironolactone (maximum dose, 50 mg/d) or placebo for 24 weeks.

      Outcomes

      Change 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.

      Results

      60 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.

      Limitations

      Low level of baseline vascular dysfunction; lack of aldosterone measurements.

      Conclusions

      24 weeks of aldosterone antagonism reduced systolic blood pressure without changing vascular function in patients with early-stage ADPKD.

      Funding

      NIDDK, NIH National Center for Advancing Translational Sciences, and the Zell Family Foundation.

      Trial Registration

      Registered at ClinicalTrials.gov with study number NCT01853553.

      Index Words

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