Division of Nephrology, Department of Medicine, University of Washington, Seattle.
Kidney Research Institute, University of Washington, Seattle.
JAMA. 2019 Nov 19;322(19):1899-1909. doi: 10.1001/jama.2019.17380.
Chronic kidney disease (CKD) is a common complication of type 2 diabetes that can lead to end-stage kidney disease and is associated with high cardiovascular risk. Few treatments are available to prevent CKD in type 2 diabetes.
To test whether supplementation with vitamin D3 or omega-3 fatty acids prevents development or progression of CKD in type 2 diabetes.
DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial with a 2 × 2 factorial design conducted among 1312 adults with type 2 diabetes recruited between November 2011 and March 2014 from all 50 US states as an ancillary study to the Vitamin D and Omega-3 Trial (VITAL), coordinated by a single center in Massachusetts. Follow-up was completed in December 2017.
Participants were randomized to receive vitamin D3 (2000 IU/d) and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid; 1 g/d) (n = 370), vitamin D3 and placebo (n = 333), placebo and omega-3 fatty acids (n = 289), or 2 placebos (n = 320) for 5 years.
The primary outcome was change in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) from baseline to year 5.
Among 1312 participants randomized (mean age, 67.6 years; 46% women; 31% of racial or ethnic minority), 934 (71%) completed the study. Baseline mean eGFR was 85.8 (SD, 22.1) mL/min/1.73 m2. Mean change in eGFR from baseline to year 5 was -12.3 (95% CI, -13.4 to -11.2) mL/min/1.73 m2 with vitamin D3 vs -13.1 (95% CI, -14.2 to -11.9) mL/min/1.73 m2 with placebo (difference, 0.9 [95% CI, -0.7 to 2.5] mL/min/1.73 m2). Mean change in eGFR was -12.2 (95% CI, -13.3 to -11.1) mL/min/1.73 m2 with omega-3 fatty acids vs -13.1 (95% CI, -14.2 to -12.0) mL/min/1.73 m2 with placebo (difference, 0.9 [95% CI, -0.7 to 2.6] mL/min/1.73 m2). There was no significant interaction between the 2 interventions. Kidney stones occurred among 58 participants (n = 32 receiving vitamin D3 and n = 26 receiving placebo) and gastrointestinal bleeding among 45 (n = 28 receiving omega-3 fatty acids and n = 17 receiving placebo).
Among adults with type 2 diabetes, supplementation with vitamin D3 or omega-3 fatty acids, compared with placebo, resulted in no significant difference in change in eGFR at 5 years. The findings do not support the use of vitamin D or omega-3 fatty acid supplementation for preserving kidney function in patients with type 2 diabetes.
ClinicalTrials.gov Identifier: NCT01684722.
慢性肾脏病（CKD）是 2 型糖尿病的常见并发症，可导致终末期肾病，并与心血管风险增加相关。目前很少有治疗方法可预防 2 型糖尿病患者的 CKD。
检测维生素 D3 或欧米伽-3 脂肪酸补充剂是否可预防 2 型糖尿病患者 CKD 的发生或进展。
设计、地点和参与者：这是一项 2×2 析因设计的随机临床试验，纳入了 2011 年 11 月至 2014 年 3 月期间从美国 50 个州招募的 1312 名 2 型糖尿病成人患者，作为 Vitamin D and Omega-3 Trial（VITAL）的一项辅助研究，由马萨诸塞州的一个中心协调。随访于 2017 年 12 月完成。
参与者被随机分配接受维生素 D3（2000IU/d）和欧米伽-3 脂肪酸（二十碳五烯酸和二十二碳六烯酸；1g/d）（n=370）、维生素 D3 和安慰剂（n=333）、安慰剂和欧米伽-3 脂肪酸（n=289）或 2 个安慰剂（n=320），疗程为 5 年。
主要结局是根据血清肌酐和胱抑素 C（eGFR）从基线到第 5 年的变化来估计肾小球滤过率（eGFR）。
在 1312 名随机分配的参与者（平均年龄 67.6 岁；46%为女性；31%为少数民族）中，934 名（71%）完成了研究。基线时 eGFR 的平均水平为 85.8（SD，22.1）mL/min/1.73 m2。与安慰剂相比，维生素 D3 组从基线到第 5 年的 eGFR 平均变化为-12.3（95%CI，-13.4 至-11.2）mL/min/1.73 m2，而安慰剂组为-13.1（95%CI，-14.2 至-11.9）mL/min/1.73 m2（差异，0.9[95%CI，-0.7 至 2.5]mL/min/1.73 m2）。与安慰剂相比，欧米伽-3 脂肪酸组 eGFR 的平均变化为-12.2（95%CI，-13.3 至-11.1）mL/min/1.73 m2，安慰剂组为-13.1（95%CI，-14.2 至-12.0）mL/min/1.73 m2（差异，0.9[95%CI，-0.7 至 2.6]mL/min/1.73 m2）。两种干预措施之间无显著交互作用。58 名参与者（n=32 名接受维生素 D3，n=26 名接受安慰剂）发生肾结石，45 名参与者（n=28 名接受欧米伽-3 脂肪酸，n=17 名接受安慰剂）发生胃肠道出血。
在 2 型糖尿病成人患者中，与安慰剂相比，补充维生素 D3 或欧米伽-3 脂肪酸在 5 年内对 eGFR 的变化没有显著差异。这些发现不支持使用维生素 D 或欧米伽-3 脂肪酸补充剂来保护 2 型糖尿病患者的肾功能。
ClinicalTrials.gov 标识符：NCT01684722。
