A Mendelian randomization study on causal effects of 25(OH) vitamin D levels on diabetic nephropathy.

ABSTRACT

BACKGROUND: Vitamin D supplementation is associated with a lower incidence of diabetic nephropathy (DN); however, whether this association is causative is uncertain. METHODS: We used two-sample Mendelian randomization to examine the causal influence of vitamin D on diabetic nephropathy in 7,751 individuals with type I diabetes-related nephropathy (T1DN) and 9,933 individuals with type II diabetes-related nephropathy (T2DN). Meanwhile, we repeated some previous studies on the influence of KIM-1 (kidney injury molecule 1) and body mass index (BMI) on DN. Additionally, to test the validity of the instruments variable for vitamin D, we conducted two negative controls Mendelian randomization (MR) on breast and prostate cancer, and a positive control MR on multiple sclerosis. RESULTS: Results of the MR analysis showed that there was no causal association between 25(OH)D with the early/later stage of T1DN (early OR = 0.903, 95%CI 0.229 to 3.555; later OR = 1.213, 95%CI 0.367 to 4.010) and T2DN (early OR = 0.588, 95%CI 0.182 to 1.904; later OR = 0.904, 95%CI 0.376 to 2.173), nor with the kidney function of patients with diabetes mellitus eGFRcyea (creatinine-based estimated GFR) (Beta = 0.007, 95%CI -0.355 to 0.369)) or UACR (urinary albumin creatinine ratio) (Beta = 0.186, 95%CI -0.961 to 1.333)). CONCLUSIONS: We found no evidence that Vitamin D was causally associated with DN or kidney function in diabetic patients.