In this application, we apply for a competitive renewal of the grant that funds the Vitamin D and Omega-3 Trial to prevent and treat Diabetic Kidney Disease (VITAL-DKD). During our initial period of funding, we launched VITAL-DKD as an ancillary study to the parent Vitamin D and Omega-3 Trial (VITAL). Specifically, to the large (N=25,875) and simple parent VITAL trial, we added kidney outcomes and accompanying clinical data to a subset of 1,322 VITAL participants with prevalent type 2 diabetes to test the effects of vitamin D3 and omega-3 fatty acids on the clinical manifestations of DKD. In this competitive renewal application, we propose to extend follow-up of our VITAL DKD ancillary study from 2 to 5 years, add measurements to stored specimens to more comprehensively evaluate treatment effects, and assess intermediate cardiovascular outcomes that complement our primary renal outcome. Our approach builds on our recruited study population and completed measurements and leverages the infrastructure of the parent VITAL trial, which is funded by the NIH to provide study treatments and basic data acquisition through 2017. We have recruited a diverse study population with type 2 diabetes that has or is at risk of DKD and is maintaining excellent adherence to study medications. To extend our study, our experienced study team will apply methods developed and successfully implemented during our initial funding period. Preliminary data demonstrate high retention and adherence rates and successful laboratory protocols. We anticipate that the additional studies proposed herein, when added to those of the initial funding period, will generate a comprehensive evaluation of the long-term effects of vitamin D3 and omega-3 fatty acids on DKD.

Public Health Relevance

The prevalence of diabetic kidney disease (DKD) is rising due to the growing burden of type 2 diabetes and despite increased application of intensive glucose control and renin-angiotensin system inhibitors. Moreover, DKD is strongly associated with cardiovascular disease and mortality. To mitigate the growing public health burden of DKD, new approaches are needed to prevent DKD as well as its progression and CVD sequelae. Vitamin D3 and omega-3 fatty acids are sufficiently accessible, inexpensive, and safe to apply to the large at- risk diabetes population if found to be effective in clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK088762-08
Application #
9414633
Study Section
Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
Program Officer
Abbott, Kevin C
Project Start
2010-09-01
Project End
2020-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
8
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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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
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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
Bansal, Nisha; Katz, Ronit; Robinson-Cohen, Cassianne et al. (2017) Absolute Rates of Heart Failure, Coronary Heart Disease, and Stroke in Chronic Kidney Disease: An Analysis of 3 Community-Based Cohort Studies. JAMA Cardiol 2:314-318
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

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