DESCRIPTION (provided by applicant): There are 26 million Americans living with kidney disease and 66 million Americans living with hypertension, the second most common cause of end-stage kidney disease requiring dialysis. Kidney disease is associated with a significantly increased risk of morbidity and mortality even before reaching end-stage kidney disease. Animal studies and observational studies in humans, including studies by investigators leading this proposed study, suggest that vitamin D and omega-3 fatty acids may be protective against kidney disease. Despite the evidence base available, there is still no definitive study testing the effects of these relatively safe nutritional supplements on kidney disease progression in humans. We now have an opportunity to provide such data in a highly feasible and cost-efficient manner. We propose to take advantage of the VITamin D and OmegA-3 TriaL (VITAL) trial to test whether vitamin D3 (at a dose of 2,000 IU/day) or omega-3 fatty acids (eicosapentaenoic acid plus docosahexaenoic acid, 1 gm/day) will preserve kidney function, as measured by serum creatinine and cystatin C, over a 4 year period. The VITAL trial is an NIH funded, placebo-controlled clinical trial randomizing 25,875 participants (men older than 50 and women older than 55 years) in a 2x2 factorial design to vitamin D3 versus placebo and omega-3 fatty acids versus placebo for 5 years to evaluate effects on cardiovascular disease and cancer events. The VITAL trial is not currently planning to evaluate kidney function in participants with hypertension. We, therefore, propose to measure serum creatinine and cystatin C and urinary albumin and creatinine at year 4 post-randomization in 4000 participants of the VITAL trial who at baseline have hypertension, no diabetes mellitus, are older than 60 years and have pre-randomization blood samples available collected by the parent study. We estimate that with these entry criteria, 25% of our 4000 patients will have an eGFR <60 ml/min/1.73m2 and 25% will be ethnic and racial minorities. We will evaluate changes in estimated GFR calculated by serum creatinine and cystatin C levels over a 4 year period, the incidence of end-stage renal disease, prevalent albuminuria at year 4 and parathyroid hormone, calcium and FGF-23 levels at baseline and year 4 in the subset with eGFR <60 ml/min/1.73m2. The proposed study takes advantage of the infrastructure and design of the VITAL trial to provide much needed data about the effects of vitamin D3 and omega-3 fatty acids on the kidney.

PUBLIC HEALTH RELEVANCE: This study will evaluate whether vitamin D3 and omega-3 fatty acids, inexpensive, over-the-counter supplements, prevent kidney disease in a large, randomized, placebo-controlled trial of individuals with hypertension. The results of the trial wil lead to recommendations for the 66 million Americans living with hypertension and at risk for kidney disease.