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

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.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_07_CJN08950621.mp3.

Keywords: ADPKD; aging; endothelial cells; oxidative stress; pulse wave velocity.

Graphical abstract

Figure 1.

Patient enrollment, randomization, and completion Consolidated Standards of Reporting Trials (CONSORT) flow diagram. This flow diagram describes enrollment, randomization, and study completion.

Figure 2.

Changes in brachial artery flow-mediated dilation and aortic pulse-wave velocity with curcumin and placebo. Brachial artery flow-mediated dilation (A) and aortic pulse-wave velocity (measured as carotid-femoral pulse-wave velocity) (B) at baseline and following 12 months of treatment with curcumin or placebo among participants completing the study (lines represent means, with individual participants shown by dots).

Figure 3.

Brachial artery flow-mediated dilation in response to inhibition of vascular oxidative stress via an acute supraphysiologic infusion of ascorbic acid. Brachial artery flow-mediated dilation following an acute supraphysiologic infusion of ascorbic acid known to inhibit superoxide production or isovolumetric saline at baseline (left) and following 12 months (right) of treatment with curcumin (A) or placebo (B). These measures were performed in a subgroup of participants ≥18 years of age. *P<0.05 by paired t test comparing saline with vitamin C within a single group at a single time point.

Figure 4.

Change in height-adjusted total kidney volume with curcumin and placebo. Height-adjusted total kidney volume at baseline and following 12 months of treatment with curcumin or placebo in the whole cohort (A), men (B), and women (C); lines represent medians, with individual participants shown by dots. *P<0.05 for group effect by linear regression with adjustment with baseline height-adjusted total kidney volume.