Causal Associations of Iron Status With the Renal Function and Diabetic Nephropathy in Patients With Diabetes Mellitus: A Two-Sample Mendelian Randomization Study.

This study was to explore the causal effect of iron status on renal function and the risk of diabetic nephropathy in diabetic patients. The data on exposures including ferritin, serum iron, transferrin saturation (TSAT), and total iron-binding capacity (TIBC) were obtained from a genome-wide association study (GWAS). The outcomes were diabetic nephropathy, Type 1 diabetes mellitus (T1DM) with renal complications, Type 2 diabetes mellitus (T2DM) with renal complications, estimated glomerular filtration rate (creatinine) (eGFRcrea) in diabetes mellitus, and urinary albumin-to-creatinine ratio (UACR) in diabetes mellitus. The causal associations of exposures and outcomes were analyzed using MR analysis with the inverse variance-weighted (IVW) method as the primary analytical method. Leave-one-out analysis was utilized to find any individual SNP associated with exposures influencing outcomes. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated. The values of all the SNPs were > 10, indicating a sufficient strength of the instrumental variables. The results from pleiotropy analysis indicated that most SNPs showed no horizontal pleiotropy ( > 0.05). The ferritin level had a causal effect on decreased eGFRcrea level in diabetes mellitus patients (OR = 0.937, 95% CI: 0.887-0.990) and increased risk of T1DM with renal complications (OR = 1.783, 95% CI: 1.005-3.162). TIBC level was causally associated with decreased risk of diabetic nephropathy (OR = 0.864, 95% CI: 0.771-0.968) and T1DM with renal complications (OR = 0.743, 95% CI: 0.603-0.916). Ferritin level had a causal effect on eGFRcrea level in diabetes mellitus patients and T1DM with renal complications. In conclusion, TIBC levels are causally linked to a lower risk of both diabetic nephropathy and T1DM with renal complications. The findings might provide a reference for using TIBC levels as a biomarker for prevention and treatment of diabetic nephropathy in the future. As the study was an MR analysis based on gene, the value of TIBC levels still should be validated in large prospective trials.