Kidney Week

Abstract: PO1580

Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD): Design and Baseline Characteristics of Participants

Session Information

• Cystic Kidney Diseases: Emerging Concepts, Biomarkers, and Clinical Trials
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1001 Genetic Diseases of the Kidneys: Cystic

Authors

• Farmer-Bailey, Heather, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States

Heather Farmer-Bailey,

• Cadnapaphornchai, Melissa A., Rocky Mountain Pediatric Kidney Center, Rocky Mountain Hospital for Children at Presbyterian St. Luke’s Medical Center, Denver, Colorado, United States

Melissa A. Cadnapaphornchai,

• You, Zhiying, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States

Zhiying You,

• George, Diana, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States

Diana George,

• Wang, Wei, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States

Wei Wang,

• Jovanovich, Anna, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States

Anna Jovanovich,

• Soranno, Danielle, Children's Hospital Colorado, Aurora, Colorado, United States

Danielle Soranno,

• Gitomer, Berenice Y., University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States

Berenice Y. Gitomer,

• Chonchol, Michel, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States

Michel Chonchol,

• Nowak, Kristen L., University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States

Kristen L. Nowak,

Background

Complications of ADPKD begin in childhood. While the hallmark of the disease is the development and continued growth of multiple renal cysts that ultimately result in loss of kidney function, cardiovascular complications are the leading cause of death. Vascular dysfunction (endothelial dysfunction and large elastic artery stiffness) is evident from a very young age and appears to involve increased oxidative stress and inflammation. Treatment options to prevent cardiovascular disease in adults with ADPKD are limited; thus, childhood may represent a key therapeutic window.

Methods

Curcumin is a safe, naturally occurring polyphenol found in the Indian spice turmeric, with a unique ability to activate transcription of key antioxidants, suppress inflammation, and reduce proliferation. We are conducting an ongoing randomized, placebo-controlled, double-blind clinical trial to assess the effect of curcumin therapy (25 mg/kg/d) on vascular function (brachial artery flow-mediated dilation [FMD_BA] and aortic pulse-wave velocity [aPWV]; co-primary outcomes) and kidney growth (change in height-adjusted total kidney volume [htTKV]) in children/young adults 6–25 yrs with ADPKD.

Results

The study is fully enrolled. Of the 68 screened participants, all 68 were randomized to receive either the curcumin or placebo. Participants ranged in age from 6-25 yrs, n=25 (37%) were children <18 yrs, and mean±S.D.estimated glomerular filtration rate was 117±16 ml/min/1.73m². FMD_BA was 9.3+0.5%, aPWV was 510+95 cm/sec, and median (IQR) htTKV was 333 (234, 475) ml/min. In the sub-group of young adults who received a supraphysiological infusion of ascorbic acid to inhibit vascular oxidative stress (n=24), FMD_BA improved vs. isovolumetric saline (13.6±5.2% vs. 11.3±4.3%), indicating baseline vascular oxidative stress. Greater baseline aPWV was independently associated with larger baseline htTKV.

Conclusion

The trial will be completed in December of 2020. This study has the potential to establish a novel, safe, and facile therapy for the treatment of arterial dysfunction, and possibly renal cystic disease, in an understudied population of children and young adults with ADPKD.

Funding

• NIDDK Support –