Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD

Background and objectivesClinical 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, & measurementsIn 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.ResultsEnrolled 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.ConclusionsCurcumin supplementation does not improve vascular function or slow kidney growth in children/young adults with ADPKD.Clinical Trial registry name and registration numberCurcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD, NCT02494141.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_07_CJN08950621.mp3