Vitamin D, Omega-3 Fail to Preserve Kidney Function in Patients with Diabetes

Supplementation with vitamin D or omega-3 fatty acid does not prevent or reduce progression of kidney disease in patients with type 2 diabetes mellitus (T2DM), according to results of study presented at Kidney Week 2019, November 7-9, Washington, DC.

Authors of the ancillary study to the Vitamin D and Omega-3 Trial (VITAL) note that although chronic kidney disease (CKD) is common among patient with T2DM, treatments to prevent or slow CKD progression are limited. Early research and observational studies suggest that vitamin D may reduce renal inflammation and fibrosis; similarly, omega-3 fatty acids have demonstrated anti-inflammatory, antithrombotic, and beneficial vascular effects.

To test whether vitamin D or omega-3 fatty acids prevent the development or progression of kidney disease in T2DM, Ian de Boer, MD, MS, professor, division of nephrology and associate director, Kidney Research Institute, University of Washington Medical School, Seattle, and colleagues randomly assigned 1312 adults with T2DM to 1 of 4 groups in a 2-by-2 factorial design for 5 years:

• Vitamin D3 (2000 IU/day) and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid; 1 g/day)

• Vitamin D3 and placebo

• Placebo and omega-3 fatty acids

• 2 placebos

Baseline mean age was 67.6 years, 46% of participants were women, and 31% were racial or ethnic minorities.

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

Baseline mean (SD) eGFR was 85.8 (22.1) mL/min/1.73m², and mean change in eGFR from baseline to year 5 was -12.7 (SD 14.6) mL/min/1.73m.²

There was no significant difference in change in eGFR comparing vitamin D₃ to placebo (difference in change 0.8 (95% CI -0.8, 2.5) mL/min/1.73m²) or omega-3 fatty acids to placebo (difference in change 0.8 (95% CI -0.8, 2.4) mL/min/1.73m²).

Mean change in eGFR was −12.3 mL/min/1.73 m² with vitamin D₃ vs −13.1 mL/min/1.73 m² with placebo, for a difference of 0.9 (95% confidence interval, −0.7 to 2.5). Similarly, the mean change for omega-3 fatty acids was −12.2 mL/min/1.73 m.²

Taken together, the findings do not support use of vitamin D or omega-3 fatty acid supplementation to preserve kidney function in patients with T2DM, researchers said in the full study report published in JAMA to coincide with the presentation at Kidney Week.

Authors of a related editorial published in JAMA said the results of this study provide “strong clinical trial-grade evidence” against meaningful kidney-protective effects in these patient, but do not rule out future investigations of the effects of vitamin D on chronic kidney disease (CKD) outcomes.

In particular, a post hoc analysis of the study suggested patients with lower baseline 25-hydroxyvitamin D levels might benefit from vitamin D supplementation, suggesting a new and sufficiently powered trial limited to that group of patients might be warranted, according to the editorial.

“Another open question is whether vitamin D supplementation might be beneficial for patients with more advanced CKD or more severe albuminuria at baseline,” they said in their editorial.

Reference: de Boer I, Zelnick LR, Hoofnagle AN, Thadhani RI, Manson JE. Effects of vitamin D and omega-3 fatty acid supplementation on kidney function and damage in type 2 diabetes.  Presented at ASN Kidney Week, November 8, 2019. Abstract FR-OR138.