Effects of Vitamin D and Fish Oil on the Kidney in Hypertensives

 描述(申请人提供)：有2600万美国人患有肾脏疾病，6600万美国人患有高血压，高血压是需要透析的终末期肾脏疾病的第二大常见原因。甚至在达到终末期肾脏疾病之前，肾脏疾病就与发病率和死亡率的显著增加有关。对人类的动物研究和观察性研究，包括领导这项拟议研究的研究人员的研究，表明维生素D和omega-3脂肪酸可能对肾脏疾病具有保护作用。尽管有证据可用，但仍然没有明确的研究来测试 这些相对安全的营养补充剂对人类肾脏疾病进展的影响。我们现在有机会以高度可行和具有成本效益的方式提供这种数据。我们建议利用维生素D和omega-3试验(VITAL)试验来测试维生素D3(每天2,000IU的剂量)或omega-3脂肪酸(二十碳五烯酸加二十二碳六烯酸，每天1克)是否在4年内保护肾功能，以血清肌酐和胱抑素C来衡量。VITAL试验是一项由NIH资助的安慰剂对照临床试验，随机选择了25875名参与者(50岁以上的男性和55岁以上的女性)，采用2x2因子设计，将维生素D3与安慰剂、omega-3脂肪酸与安慰剂进行对比，为期5年，以评估对心血管疾病和癌症事件的影响。VITAL试验目前没有计划评估高血压参与者的肾功能。因此，我们建议在VITAL试验的4000名参与者中，在随机后的第4年测量血清肌酐和胱抑素C以及尿白蛋白和肌酐，这些参与者在基线时有高血压，没有糖尿病，年龄超过60岁，并且有母公司研究收集的随机前血液样本。我们估计，在我们的4000名患者中，有25%的患者的EGFR为60ml/min/1.73m2，25%的患者将是少数族裔。我们将评估评估GFR的变化，计算方法是4年内的血肌酐和胱抑素C水平、终末期肾病的发病率、第4年普遍的蛋白尿以及基线和第4年的甲状旁腺激素、钙和成纤维细胞生长因子-23水平。这项拟议的研究利用VITAL试验的基础设施和设计，提供了关于维生素D3和omega-3脂肪酸对肾脏影响的迫切需要的数据。

 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.