Objective: To investigate the diabetes-specific association between non-HDL/HDL cholesterol ratio (NHHR) and urinary albumin-to-creatinine ratio (UACR), and its nonlinear threshold effect in chronic kidney disease (CKD) stages.
Methods: This cross-sectional study included 10,613 U.S. adults(aged 20-70 years, estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2) from NHANES 2015-2020. NHHR was calculated as the difference between total cholesterol and HDL-C divided by HDL-C. To explore the relationship between NHHR and UACR, a multivariable logistic regression model, smoothed curve fitting and subgroup analyses were employed.
Results: Each 1-unit NHHR increase elevated UACR by 4.46 mg/g overall(95% CI: 1.13-7.78, P = 0.009). Crucially, NHHR-UACR association wasexclusive to diabetics(β = 23.56 mg/g, 95% CI: 8.59-38.54, P < 0.001) with no significance in non-diabetics(P for interaction < 0.001). A nonlinear pattern emerged and intensified with declining renal function: Stage 1 showed a linear relationship(P = 0.426), Stage 2 demonstrated marginal nonlinearity(P = 0.031), and Stage 3 displayed a markedly nonlinear relationship(P < 0.001),characterized by an accelerated increase in UACR beyond an NHHR of approximately 3.5. Effect modification was significant by ethnicity (stronger in Non-Hispanic Blacks, P = 0.016) and sex(greater in females, P = 0.048).
Conclusion: NHHR associates with albuminuriaexclusively in diabetesand exhibits anonlinear pattern in CKD stage 3. These findings indicate diabetes-specific renal injury patterns and CKD stage-dependent pathophysiological mechanisms.
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