Effect of Vitamin D and Omega-3 Fatty Acid Supplementation on Kidney Function in Patients With Type 2 Diabetes: A Randomized Clinical Trial

Abstract

Importance: 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.

Objective: 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.

Interventions: 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.

Main outcomes and measures: The primary outcome was change in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) from baseline to year 5.

Results: 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).

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT01684722.

Figure 1.. Participant Flow in the Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease

eGFR indicates estimated glomerular filtration rate. ^aOf the 97 lost to follow-up, 1 was also missing baseline eGFR. ^bOf the 94 lost to follow-up, 1 was also missing baseline eGFR.

Figure 2.. Distributions of eGFR and Urine ACR Over the Course of the Study According to Treatment Assignment

ACR indicates urine albumin-creatinine ratio; eGFR, estimated glomerular filtration rate. The center horizontal line in each box indicates the median; top and bottom box borders indicate the first and third quartiles, respectively. Whiskers depict the most extreme observation within 1.5× the interquartile range (IQR) of the nearest quartile; circles show all points lying beyond 1.5× the IQR of the nearest quartile. Urine ACR plots are shown on a log scale. Numbers shown are participants contributing data at each time point.

Figure 3.. Effects of Vitamin D vs Placebo on Change in eGFR Among Participant Subgroups

ACR indicates urine albumin-creatinine ratio; eGFR, estimated glomerular filtration rate. Body mass index is calculated as weight in kilograms divided by height in meters squared. Estimates are differences in change in eGFR from baseline to year 5 comparing active treatment with placebo, adjusted for age, sex, and baseline urine ACR.

Figure 4.. Effects of Omega-3 Fatty Acids vs Placebo on Change in eGFR Among Participant Subgroups

ACR indicates urine albumin-creatinine ratio; DHA, docosahexaenoic acid; eGFR, estimated glomerular filtration rate; EPA, eicosapentaenoic acid; hsCRP, high-sensitivity C-reactive protein. Estimates are differences in change in eGFR from baseline to year 5 comparing active treatment with placebo, adjusted for age, sex, and baseline urine ACR.