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Original ArticleCystic Kidney Disease
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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 and Michel Chonchol
CJASN February 2022, 17 (2) 240-250; DOI: https://doi.org/10.2215/CJN.08950621
Kristen L. Nowak
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Heather Farmer-Bailey
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Wei Wang
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Zhiying You
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Cortney Steele
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Melissa A. Cadnapaphornchai
2Rocky Mountain Pediatric Kidney Center, Rocky Mountain Hospital for Children at Presbyterian St. Luke’s Medical Center, Denver, Colorado
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Jelena Klawitter
3Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Nayana Patel
4Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Diana George
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Anna Jovanovich
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
5Department of Nephrology, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado
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Danielle E. Soranno
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
6Children’s Hospital Colorado, Aurora, Colorado
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Berenice Gitomer
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Michel Chonchol
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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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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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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  • oxidative stress
  • pulse wave velocity
  • aging
  • endothelial cells
  • ADPKD
  • Received June 29, 2021.
  • Accepted December 9, 2021.
  • Copyright © 2022 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 17 (2)
Clinical Journal of the American Society of Nephrology
Vol. 17, Issue 2
February 2022
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Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD
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
CJASN Feb 2022, 17 (2) 240-250; DOI: 10.2215/CJN.08950621

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Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD
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
CJASN Feb 2022, 17 (2) 240-250; DOI: 10.2215/CJN.08950621
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Original Article

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Cystic Kidney Disease

  • Health Disparities in Autosomal Dominant Polycystic Kidney Disease (ADPKD) in the United States
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  • Correction: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled Trial
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Keywords

  • oxidative stress
  • pulse wave velocity
  • aging
  • endothelial cells
  • ADPKD

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