Association of anemia with diabetic kidney disease in adults with type 2 diabetes: A cross-sectional NHANES study and 2-sample Mendelian randomization analysis

Anemia commonly accompanies chronic kidney disease, but the direction of the association between anemia and diabetic kidney disease remains uncertain. We examined the association using cross-sectional NHANES data and explored potential causal associations using 2-sample Mendelian randomization. We conducted a cross-sectional analysis of adults with type 2 diabetes from the 2009–2018 NHANES cycles. Survey-weighted logistic regression and restricted cubic spline analyses were used to evaluate the associations of anemia and hemoglobin levels with presumed DKD, albuminuria, and reduced eGFR. Two-sample Mendelian randomization was subsequently performed to explore potential causal associations between anemia-related phenotypes and DKD. Anemia was more prevalent among participants with presumed DKD than among those without presumed DKD (21.6% vs 9.6%). In survey-weighted regression models, anemia was associated with higher odds of presumed DKD, albuminuria, and reduced eGFR, whereas higher hemoglobin levels were inversely associated with these outcomes. Restricted cubic spline analyses indicated L-shaped associations. Mendelian randomization estimates suggested potential associations of genetically predicted general anemia, iron deficiency anemia, and vitamin B12 deficiency anemia with DKD; however, significant heterogeneity was observed across SNP-specific estimates. Anemia was associated with higher odds of presumed DKD, albuminuria, and reduced eGFR among adults with type 2 diabetes. Mendelian randomization analyses provided suggestive evidence of potential causal associations between anemia-related phenotypes and DKD. However, the cross-sectional design, relaxed SNP-selection threshold, and significant heterogeneity warrant cautious interpretation and independent validation.