Abstract
Depression and diabetic kidney disease (DKD) are leading global health burdens that frequently co-occur. Using Global Burden of Disease (GBD) 2023, National Health and Nutrition Examination Survey (NHANES) 2013-March 2020, and Mendelian randomization (MR), we investigated epidemiological patterns and genetic underpinnings of this relationship. GBD data indicate a rising DKD burden and high depression rates, especially in women and younger adults. NHANES demonstrated a strong, graded cross-sectional association between depressive symptom severity and prevalent DKD, with moderately severe-to-severe symptoms conferring the highest odds of disease. MR analyses, however, yielded predominantly null findings. Although a nominal association between depressed affect and DKD was observed in European ancestry populations, this estimate attenuated following sensitivity analyses and did not provide robust evidence for a direct causal relationship. Integrating mental health screening into diabetes care may mitigate the combined burden of these conditions.