Although often considered to be a disease of adults, complications of ADPKD begin in childhood. While the hallmark of ADPKD is the development and continued growth of multiple renal cysts that result in ultimate loss of kidney function, the leading cause of death among affected patients is cardiovascular in nature. Vascular dysfunction (endothelial dysfunction and large elastic artery stiffness) is evident very early in te course of the disease and appears to involve increased oxidative stress and inflammation. Treatment options to prevent CVD in adults with ADPKD are limited, thus childhood may represent a key therapeutic window. Curcumin is a safe, naturally occurring polyphenol found in the Indian spice turmeric that has a unique ability to activate transcription of key antioxidants, suppress inflammation, and reduce proliferation.
Aim 1 will assess the efficacy of curcumin (25 mg/kg/day) for improving vascular function in children and young adults (6-22 years of age) with ADPKD, using a 1 year randomized, placebo-controlled, double-blind trial.
Aim 2 will determine (in a sub-group of patients 18-22 years of age), if improvements are associated with reduced oxidative stress and inflammation, utilizing state of the art mass spectrometry methods. A third exploratory aim will assess changes in total kidney volume using MRI scans. This study has the potential to establish a novel, safe, and easy to deliver therapy for the treatment of arterial dysfunction, and possibly renal cystic disease, in an understudied population of children and young adults with ADPKD.

Public Health Relevance

The proposed research will determine the effectiveness of curcumin, a naturally occurring substance found in the Indian spice turmeric, for improving the health and function of arteries in children and young adults with autosomal dominant polycystic kidney disease (ADPKD). The study also will provide insight into how curcumin improves artery health by determining the physiological mechanisms (biological reasons) involved and offer exploratory evidence if curcumin can slow kidney growth.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
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Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
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Rankin, Tracy L
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University of Colorado Denver
Internal Medicine/Medicine
Schools of Medicine
United States
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Nowak, Kristen L; Chonchol, Michel; You, Zhiying et al. (2018) Affected parent sex and severity of autosomal dominant polycystic kidney disease: a retrospective cohort study?. Clin Nephrol 89:196-204
Nowak, Kristen L; You, Zhiying; Gitomer, Berenice et al. (2018) Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol 29:571-578
Nowak, Kristen L; Chonchol, Michel (2018) Does inflammation affect outcomes in dialysis patients? Semin Dial 31:388-397
Nowak, Kristen L; Wang, Wei; Farmer-Bailey, Heather et al. (2018) Vascular Dysfunction, Oxidative Stress, and Inflammation in Autosomal Dominant Polycystic Kidney Disease. Clin J Am Soc Nephrol 13:1493-1501
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Nowak, Kristen L; Yaffe, Kristine; Orwoll, Eric S et al. (2018) Serum Sodium and Cognition in Older Community-Dwelling Men. Clin J Am Soc Nephrol 13:366-374
Nowak, Kristen L; Rossman, Matthew J; Chonchol, Michel et al. (2018) Strategies for Achieving Healthy Vascular Aging. Hypertension 71:389-402
Nowak, Kristen L; Bartz, Traci M; Dalrymple, Lorien et al. (2017) Fibroblast Growth Factor 23 and the Risk of Infection-Related Hospitalization in Older Adults. J Am Soc Nephrol 28:1239-1246
Nowak, Kristen L; Farmer, Heather; Cadnapaphornchai, Melissa A et al. (2017) Vascular dysfunction in children and young adults with autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 32:342-347
Jalal, Diana I; Decker, Emily; Perrenoud, Loni et al. (2017) Vascular Function and Uric Acid-Lowering in Stage 3 CKD. J Am Soc Nephrol 28:943-952

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