Serum High-Density Lipoprotein Cholesterol Levels and the Risk of Kidney Function Decline: The Japan Specific Health Checkups (J-SHC) Study

Aims: Both low and high serum levels of high-density lipoprotein cholesterol (HDL-C) were reported to be associated with adverse kidney outcomes. However, this association has not been well investigated in the general Japanese population. Methods: This nationwide longitudinal study used data from the Japan Specific Health Checkups Study conducted between 2008-2014. The association between serum HDL-C levels and 40% decline in estimated glomerular filtration rate (eGFR) was analyzed using Cox regression analysis. Trajectories of eGFR were compared using mixed-effects model. Results: Among 768,495 participants, 6,249 developed 40% decline in eGFR during the median follow-up period of 34.6 (interquartile range: 14.8-48.4) months. Using serum HDL-C levels of 40-59 mg/dL as a reference, the adjusted hazard ratios (95% confidence intervals) for the kidney outcome of serum HDL-C levels of <40, 60-79 and >= 80 mg/dL were 1.26 (1.14-1.39), 0.91 (0.86-0.96), and 0.86 (0.78-0.93), respectively. Restricted cubic spline analysis showed that HDL-C levels of less than approximately 60 mg/dL were associated with an increased risk of kidney outcomes. Subgroup analysis showed that baseline eGFR and proteinuria modified the effects of serum HDL-C levels on kidney outcomes. The mixed-effects model showed that the lower category of HDL-C level was associated with a higher eGFR decline rate (p for interaction <0.001). Conclusions: Low HDL-C levels were associated with kidney function decline; however, high HDL-C levels were not associated with adverse kidney outcomes in the general Japanese population.