Association between the uric acid to high-density lipoprotein cholesterol ratio and diabetic kidney disease in U.S. adults with type 2 diabetes

The uric-acid-to- high-density lipoprotein-cholesterol ratio (UHR) combines 2 circulating biomarkers related to metabolic and inflammatory processes. Its association with prevalent diabetic kidney disease (DKD) was examined in U.S. adults with type 2 diabetes mellitus. This study aimed to examine the cross-sectional association between UHR and prevalent DKD and assess its incremental discrimination beyond the specified covariate model. We analyzed 4010 adults with type 2 diabetes mellitus from NHANES 2009 to 2018 using the complex survey design. DKD was defined as urinary albumin-to-creatinine ratio ≥30 mg/g and/or estimated glomerular filtration rate <60 mL/min/1.73 m2, calculated using the 2009 chronic kidney disease epidemiology collaboration equation without its race coefficient. Strict DKD required both abnormalities; severe DKD required urinary albumin-to-creatinine ratio ≥300 mg/g. Model 3 was the primary confounder-adjusted model, and model 4 added laboratory indicators as an extended sensitivity analysis. Supplementary analyses assessed nonlinearity, discrimination and graphical calibration. Exploratory unweighted category-based net reclassification improvement used 500 bootstrap replicates and percentile confidence intervals. Of 4010 participants, 1576 had study-defined DKD; the weighted prevalence was 35.4%. In model 3, the highest versus lowest ln-UHR quartile had an odds ratio of 2.43 (95% confidence interval 1.75-3.38) for original DKD, 4.55 (2.81-7.35) for strict DKD and 2.82 (1.57-5.06) for severe DKD. Estimates were attenuated in model 4, with the severe-DKD contrast no longer meeting the 0.05 threshold. The laboratory-adjusted spline indicated nonlinearity (P < .001). In the separate laboratory-inclusive discrimination analysis, adding ln-UHR increased apparent area under the curve from 0.75 to 0.76; the unweighted net reclassification improvement was 1.9% (95% confidence interval 0.8%-3.1%). Higher UHR was associated with prevalent DKD after adjustment for the selected potential confounders. Supplementary analyses showed a small increase in apparent discrimination. These cross-sectional findings require prospective investigation and independent external validation before use for future risk prediction or clinical screening.