Cross-sectional association of the uric acid-to-HDL cholesterol ratio with diabetic kidney disease in patients with type 2 diabetes
Background Diabetic kidney disease (DKD) is a major complication of type 2 diabetes (T2D) and is closely linked to metabolic dysregulation. The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) integrates urate-related purine metabolism and high-density lipoprotein cholesterol (HDL-C)-related lipid metabolism, two metabolic signals potentially related to kidney injury. This study examined the cross-sectional association between UHR and prevalent DKD in patients with T2D. Methods This study included a primary clinical cohort of 912 patients with T2D and an external validation cohort from the National Health and Nutrition Examination Survey (NHANES; n = 2,738). Multivariable logistic regression was used to assess the association between UHR and prevalent DKD. Restricted cubic spline (RCS) analyses evaluated exposure-response patterns. Subgroup, interaction, and joint analyses were performed to examine the association across clinical strata. Results In the primary cohort, DKD prevalence increased from 20.52% in the lowest UHR quartile to 55.26% in the highest quartile (P < 0.001). After full adjustment, each 1-SD increase in UHR was associated with more than 2-fold higher odds of DKD (OR, 2.22; 95% CI, 1.80–2.77; P < 0.001). Compared with Q1, the adjusted ORs for Q2, Q3, and Q4 were 1.29, 2.32, and 6.73, respectively. The trend across quartiles was significant (P for trend < 0.001). RCS analyses showed positive overall associations between UHR and DKD. The positive association was generally observed across predefined subgroups, with nominal evidence of interaction by body mass index (BMI) and insulin use. In NHANES, 1,067 of 2,738 participants had DKD. External validation showed directionally consistent results. Higher odds of DKD were observed per 1-SD increase in UHR (OR, 1.44; 95% CI, 1.23–1.68; P < 0.001) and in Q4 vs. Q1 (OR, 2.61; 95% CI, 1.79–3.79; P < 0.001). Survey-weighted RCS showed a positive association without significant non-linearity. Conclusion Higher UHR was associated with greater odds of prevalent DKD in the hospital-based T2D cohort, with directionally consistent findings in the NHANES validation cohort.