Kidney Week

Abstract: FR-PO304

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

Session Information

• Cystic Kidney Diseases - II
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 801 Cystic Kidney Diseases

Authors

• Nowak, Kristen L., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Kristen L. Nowak,

• Gitomer, Berenice Y., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Berenice Y. Gitomer,

• Farmer-Bailey, Heather, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Heather Farmer-Bailey,

• Wang, Wei, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Wei Wang,

• George, Diana, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Diana George,

• Chonchol, Michel, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Michel Chonchol,

• Malaczewski, Mikaela R., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Mikaela R. Malaczewski,

Background

Arterial dysfunction, featuring impaired vascular endothelial function and increased large-elastic artery stiffness, is evident early 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 are arterial stiffness. We hypothesized that aldosterone antagonism would reduce arterial dysfunction in patients with early-stage ADPKD.

Methods

In a randomized, controlled, double-blind trial, n=60 adults 30-55 years of age with ADPKD, normal kidney function (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m²), and receiving the maximum tolerable dose of an angiotensin converting enzyme inhibitor were randomized to receive either spironolactone (titrated to maximum dose of 50 mg/day) or placebo for 6 months. The primary endpoints were change in vascular endothelial function, measured as brachial artery flow-mediated dilation (FMD_BA) and arterial stiffness, measured as carotid-femoral pulse-wave velocity (CFPWV).

Results

Participants were 34±10 (mean±s.d.) years of age, 53% female and 80% White, with an eGFR of 94+21ml/min/1.73m². Spironolactone did not change FMD_BA (baseline: 8.0±5.5%, 6 months: 7.7±4.1%; placebo: baseline: 8.4±6.2%, 6 months: 7.9±4.3%; p≥0.63), but reduced CFPWV (baseline: 640±127 cm/sec, 6 months: 4: 603±101 cm/sec; p<0.05) with no change in the placebo group (baseline: 659+138 cm/sec, 6 months: 661±132 cm/sec; p=0.90). Brachial systolic blood pressure (SBP) was also reduced in the spironolactone group (baseline: 124±13 mmHg, 6 months: 117±11 mmHg; p<0.05) with no change in the placebo group (p=0.50). Spironolactone also reduced brachial and carotid pulse pressure, carotid SBP, and carotid augmentation index (p<0.05), with no changes in the placebo group.

Conclusion

Six months of aldosterone antagonism with spironolactone reduced arterial stiffness and SBP without changing vascular endothelial function in patients with early-stage ADPKD.

Funding

• NIDDK Support