Low levels of high-density lipoprotein cholesterol increase the risk of incident kidney disease and its progression

Available experimental evidence suggests a role for high-density lipoprotein cholesterol (HDL-C) in incident chronic kidney disease (CKD) and its progression. However, clinical studies are inconsistent. We therefore built a cohort of 1,943,682 male US veterans and used survival models to examine the association between HDL-C and risks of incident CKD or CKD progression (doubling of serum creatinine, eGFR decline of 30% or more), or a composite outcome of ESRD, dialysis, or renal transplantation. Models were adjusted for demographics, comorbid conditions, eGFR, body mass index, lipid parameters, and statin use over a median follow-up of 9 years. Compared to those with HDL-C of 40 mg/dl or more, low HDL-C (under 30 mg/dl) was associated with increased risk of incident eGFR under 60 ml/min/1.73 m² (hazard ratio: 1.18; confidence interval: 1.17-1.19) and risk of incident CKD (1.20; 1.18-1.22). Adjusted models demonstrate an association between low HDL-C and doubling of serum creatinine (1.14; 1.12-1.15), eGFR decline of 30% or more (1.13; 1.12-1.14), and the composite renal end point (1.08; 1.06-1.11). Cubic spline analyses of the relationship between HDL-C levels and renal outcomes showed a U-shaped relationship, where risk was increased in lowest and highest deciles of HDL-C. Thus, a significant association exists between low HDL-C levels and risks of incident CKD and CKD progression. Further studies are needed to explain the increased risk of adverse renal outcomes in patients with high HDL-C.