Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled Trial

Kristen L. Nowak; Heather Farmer-Bailey; Wei Wang; Zhiying You; Cortney Steele; Melissa A. Cadnapaphornchai; Jelena Klawitter; Nayana Patel; Diana George; Anna Jovanovich; Danielle E. Soranno; Berenice Gitomer; Michel Chonchol

doi:10.2215/CJN.08950621

This article has a correction. Please see:

Correction: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled Trial - June 01, 2022

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Visual Abstract

Abstract

Background and objectives Clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD), including evidence of vascular dysfunction, can begin in childhood. Curcumin is a polyphenol found in turmeric that reduces vascular dysfunction in rodent models and humans without ADPKD. It also slows kidney cystic progression in a murine model of ADPKD. We hypothesized that oral curcumin therapy would reduce vascular endothelial dysfunction and arterial stiffness in children/young adults with ADPKD.

Design, setting, participants, & measurements In a randomized, placebo-controlled, double-blind trial, 68 children/young adults 6–25 years of age with ADPKD and eGFR>80 ml/min per 1.73 m² were randomized to either curcumin supplementation (25 mg/kg body weight per day) or placebo administered in powder form for 12 months. The coprimary outcomes were brachial artery flow-mediated dilation and aortic pulse-wave velocity. We also assessed change in circulating/urine biomarkers of oxidative stress/inflammation and kidney growth (height-adjusted total kidney volume) by magnetic resonance imaging. In a subgroup of participants ≥18 years, vascular oxidative stress was measured as the change in brachial artery flow-mediated dilation following an acute infusion of ascorbic acid.

Results Enrolled participants were 18±5 (mean ± SD) years, 54% were girls, baseline brachial artery flow-mediated dilation was 9.3±4.1% change, and baseline aortic pulse-wave velocity was 512±94 cm/s. Fifty-seven participants completed the trial. Neither coprimary end point changed with curcumin (estimated change [95% confidence interval] for brachial artery flow-mediated dilation [percentage change]: curcumin: 1.14; 95% confidence interval, −0.84 to 3.13; placebo: 0.33; 95% confidence interval, −1.34 to 2.00; estimated difference for change: 0.81; 95% confidence interval, −1.21 to 2.84; P=0.48; aortic pulse-wave velocity [centimeters per second]: curcumin: 0.6; 95% confidence interval, −25.7 to 26.9; placebo: 6.5; 95% confidence interval, −20.4 to 33.5; estimated difference for change: −5.9; 95% confidence interval, −35.8 to 24.0; P=0.67; intent to treat). There was no curcumin-specific reduction in vascular oxidative stress or changes in mechanistic biomarkers. Height-adjusted total kidney volume also did not change as compared with placebo.

Conclusions Curcumin supplementation does not improve vascular function or slow kidney growth in children/young adults with ADPKD.

Clinical Trial registry name and registration number Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD, NCT02494141.

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Received June 29, 2021.
Accepted December 9, 2021.

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