We propose a randomized, placebo-controlled clinical trial of vitamin D3 (cholecalciferol) and omega-3 fatty acids (eicosapentaenoic acid plus docosahexaenoic acid) to prevent the development and progression of diabetic kidney disease (DKD). Persons with diabetes are at high risk of developing kidney disease, and DKD is both the leading cause of end stage renal disease in the developed world and a potent amplifier of cardiovascular disease risk. Vitamin D and omega-3 fatty acids are promising interventions for DKD prevention and treatment, based on results of animal-experimental models and early human studies. Because these interventions are relatively safe, inexpensive, and widely available, they may offer opportunity to substantially reduce the burden of DKD in large populations.
We aim to test whether vitamin D3 and/or omega-3 fatty acids prevent progression of albuminuria and loss of glomerular filtration rate, two complementary manifestations of DKD, over 4 years of treatment. To effectively and efficiently test study hypotheses, we propose an ancillary study to the Vitamin D and Omega-3 Trial (VITAL), an NIH-funded randomized clinical trial. In VITAL, 20,000 participants (men ages e 60 years, women ages e 65 years) will be randomly assigned in a 2x2 factorial design to vitamin D3 (cholecalciferol) 1600 IU daily versus placebo, and to eicosapentaenoic acid 500 mg plus docosahexaenoic acid 500 mg daily versus placebo, and followed for a mean of 5 years to assess effects on cardiovascular disease and cancer events. Leveraging the established infrastructure of VITAL, we propose to identify and recruit a sub-cohort of 1,500 VITAL participants with diabetes at baseline and to ascertain effects of study interventions on albuminuria and glomerular filtration rate in this group. Following the simple and cost-efficient design of the parent VITAL trial, biospecimens will be collected locally and delivered to the VITAL central laboratory by mail. First morning voids will be collected at baseline and year 4 for measurement of urine albumin-creatinine ratio. Blood samples will be collected simultaneously for measurement of glomerular filtration rate (using serum creatinine and cystatin C), 25- hydroxyvitamin D, eicosapentaenoic acid plus docosahexaenoic acid, C-reactive protein, and hemoglobin A1c. The proposed studies are designed to determine whether vitamin D3 and/or omega-3 fatty acids have causal and clinically relevant effects on the development and progression of DKD.
Diabetic kidney disease (DKD) is a cause of substantial morbidity and mortality. Despite widespread use of intensive glycemic control and renin-angiotensin-aldosterone system inhibitors, renal and cardiovascular consequences of DKD remain common. This study will evaluate whether vitamin D3 and/or omega-3 fatty acids are safe and effective interventions to reduce the burden of DKD among the large and growing diabetic population.
|de Boer, Ian H; Zelnick, Leila R; Lin, Julie et al. (2018) Vitamin D and omega-3 trial to prevent and treat diabetic kidney disease: Rationale, design, and baseline characteristics. Contemp Clin Trials 74:11-17|
|Lamprea-Montealegre, Julio A; Zelnick, Leila R; Hall, Yoshio N et al. (2018) Prevalence of Hypertension and Cardiovascular Risk According to Blood Pressure Thresholds Used for Diagnosis. Hypertension 72:602-609|
|de Boer, Ian H; Gao, Xiaoyu; Bebu, Ionut et al. (2017) Biomarkers of tubulointerstitial damage and function in type 1 diabetes. BMJ Open Diabetes Res Care 5:e000461|
|de Boer, Ian H; Kahn, Steven E (2017) SGLT2 Inhibitors-Sweet Success for Diabetic Kidney Disease? J Am Soc Nephrol 28:7-10|
|Kendrick, Jessica B; Zelnick, Leila; Chonchol, Michel B et al. (2017) Serum Bicarbonate Is Associated with Heart Failure in the Multi-Ethnic Study of Atherosclerosis. Am J Nephrol 45:118-126|
|de Boer, Ian H; Utzschneider, Kristina M (2017) The kidney's role in systemic metabolism-still much to learn. Nephrol Dial Transplant 32:588-590|
|Zelnick, Leila R; Weiss, Noel S; Kestenbaum, Bryan R et al. (2017) Diabetes and CKD in the United States Population, 2009-2014. Clin J Am Soc Nephrol 12:1984-1990|
|Robinson-Cohen, Cassianne; Zelnick, Leila R; Hoofnagle, Andrew N et al. (2017) Associations of Vitamin D-Binding Globulin and Bioavailable Vitamin D Concentrations With Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA). J Clin Endocrinol Metab 102:3075-3084|
|Hallan, Stein; Afkarian, Maryam; Zelnick, Leila R et al. (2017) Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD Patients. EBioMedicine 26:68-77|
|Ahmad, Iram; Zelnick, Leila R; Robinson, Nicole R et al. (2017) Chronic kidney disease and obesity bias surrogate estimates of insulin sensitivity compared with the hyperinsulinemic euglycemic clamp. Am J Physiol Endocrinol Metab 312:E175-E182|
Showing the most recent 10 out of 46 publications