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Kidney Week

Abstract: PO1260

Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Nowak, Kristen L., Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • Farmer-Bailey, Heather, Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • Wang, Wei, Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • You, Zhiying, Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • Steele, Cortney, Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • Cadnapaphornchai, Melissa A., Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • Klawitter, Jelena, Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • Patel, Nayana, Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • George, Diana, Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • Jovanovich, Anna, Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • Soranno, Danielle, Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • Gitomer, Berenice Y., Rocky Mountain Hospital for Children, Denver, Colorado, United States
  • Chonchol, Michel, Rocky Mountain Hospital for Children, Denver, Colorado, United States
Background

Clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD) can begin in childhood, including evidence of vascular dysfunction, an important predictor of cardiovascular events and mortality. Curcumin is a polyphenol found in turmeric that reduces vascular dysfunction in rodent models and humans free from ADPKD. It also slows kidney cystic progression in a murine model of ADPKD.

Methods

We hypothesized that curcumin supplementation would reduce vascular dysfunction (brachial artery flow-mediated dilation [FMDBA] and aortic pulse-wave velocity [aPWV]) in children and young adults with ADPKD. In a prospective, randomized, controlled, double-blind trial, n=68 participants 6-25 years of age with ADPKD and an estimated glomerular filtration rate >80 mL/min/1.73 m2 were randomized to receive either curcumin supplementation (25 mg/kg body weight/day) or placebo administered in powder form for 12 months. We also assessed change in circulating and urine biomarkers of oxidative stress/inflammation and kidney growth (height-adjusted total kidney volume [htTKV]; exploratory endpoint) by magnetic resonance imaging. In a sub-group of participants ≥18 years, we also assessed vascular oxidative stress as the change in FMDBA following an acute infusion of ascorbic acid.

Results

Fifty-seven participants completed the trial. Participants were 18±5 (mean±s.d.) years, 55% female, and 85% non-Hispanic White. The co-primary endpoint, FMDBA (%△), did not change in the curcumin group (baseline: 9.4±4.1; 12-months: 10.6±3.9), as compared to the placebo group (baseline: 8.9±4.0; 12-months: 9.3±4.5; p=0.22), nor did the other co-primary endpoint, aPWV (cm/sec) (curcumin: 517±106; 12-months: 517±81; placebo: baseline: 518±82 cm/sec 12-months: 525±95 cm/sec; p=0.53). There was no curcumin specific reduction in vascular oxidative stress, nor any changes in mechanistic biomarkers. htTKV also did not change over the 12-month study with curcumin administration as compared to placebo.

Conclusion

Curcumin supplementation does not reduce vascular dysfunction or slow kidney growth in children/young adults with ADPKD.

Funding

  • NIDDK Support