Association between neutrophil-to-HDL cholesterol ratio and diabetic nephropathy in adults with diabetes mellitus

Renal complications in diabetes impose substantial morbidity globally, yet early risk stratification remains challenging. The neutrophil-to-HDL cholesterol ratio (NHR) represents an integrated biomarker reflecting both immune activation and dyslipidemia, with neutrophilia promoting renal inflammation and low HDL-C impairing renoprotective mechanisms. We evaluated whether NHR is associated with diabetic nephropathy (DN) in a population-based cross-sectional study. We analyzed 2005 diabetic adults from six NHANES cycles (2007-2018). DN was defined as microalbuminuria (UACR ≥ 30 mg/g) or reduced eGFR (<60 mL/min/1.73m2) calculated via CKD-EPI 2021. NHR was computed as the ratio of neutrophil count to HDL-C concentration. Multivariable logistic regression with sequential covariate adjustment (demographics, socioeconomic factors, and comorbidities) was used to examine NHR-DN associations. Quartile-based dose-response analysis and restricted cubic spline modeling were additionally performed to characterize the association shape. DN prevalence reached 37.31% (n = 748). Individuals with nephropathy exhibited 15% higher median NHR (3.691 vs. 3.211, P < .001). Fully adjusted models revealed that per-unit NHR elevation increased DN odds by 22.48% (OR 1.2248, 95%CI 1.1533-1.3017, P < .001). Quartile analysis demonstrated dose-response relationships: top quartile participants showed 2.70-fold higher nephropathy risk versus bottom quartile (OR 2.6967, 95%CI 1.9965-3.6556, p-trend < 0.001). Higher NHR independently correlates with diabetic nephropathy presence in US adults. This readily calculated index combining inflammatory and metabolic dimensions may enhance clinical risk assessment. These observational findings suggest that NHR may serve as a complementary marker to support kidney disease risk stratification in diabetic patients, pending confirmation by prospective studies.