Systemic inflammation appears to contribute to the relationship between hyperuricemia and DKD, according to a cross-sectional analysis published in Metabolism Open. The study assessed whether the Aggregate Index of Systemic Inflammation (AISI) mediated the association between serum UA and DKD in adults with diabetes.

The evaluation included 1,716 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. Logistic regression models examined associations among UA, AISI, and DKD after adjustment for clinical confounders. Mediation analysis quantified the indirect effect of AISI. A random forest model, interpreted using SHAP values, assessed DKD prediction performance.

Higher UA was associated with increased DKD risk (adjusted odds ratio 1.14; 95% CI 1.04–1.26). UA positively correlated with AISI (β = 0.0356; p = 0.0058), and elevated AISI was independently associated with DKD (odds ratio 1.25 per SD increase in ln-AISI; 95% CI 1.10–1.42). AISI mediated 10.94% of the UA–DKD association, indicating that inflammation contributes to but does not fully explain this pathway. Incorporating AISI into predictive models resulted in modest performance gains, without outperforming conventional clinical risk factors.

These findings support systemic inflammation as a partial mechanistic link between elevated uric acid and renal injury in diabetes. Traditional clinical risk factors remain central to diabetic kidney disease prediction.