Kidney function is associated with an altered protein composition of high-density lipoprotein

Patients with chronic kidney disease (CKD) exhibit a myriad of metabolic derangements, including dyslipidemia characterized by low plasma concentrations of high-density lipoprotein (HDL)-associated cholesterol. However, the effects of kidney disease on HDL composition have not been comprehensively determined. Here we used a targeted mass spectrometric approach to quantify 38 proteins contained in the HDL particles within a CKD cohort of 509 participants with a broad range of estimated glomerular filtration rates (eGFRs) (CKD stages I-V, and a mean eGFR of 45.5 mL/min/1.73m²). After adjusting for multiple testing, demographics, comorbidities, medications, and other characteristics, eGFR was significantly associated with differences in four HDL proteins. Compared to participants with an eGFR of 60 mL/min/1.73m² or more, those with an eGFR under 15 mL/min/1.73m² exhibited 1.89-fold higher retinol-binding protein 4 (95% confidence interval 1.34-2.67), 1.52-fold higher apolipoprotein C-III (1.25-1.84), 0.70-fold lower apolipoprotein L1 (0.55-0.92), and 0.64-fold lower vitronectin (0.48-0.85). Although the HDL apolipoprotein L1 was slightly lower among African Americans than among Caucasian individuals, the relationship to eGFR did not differ by race. After adjustment, no HDL-associated proteins associated with albuminuria. Thus, modest changes in the HDL proteome provide preliminary evidence for an association between HDL proteins and declining kidney function, but this needs to be replicated. Future analyses will determine if HDL proteomics is indeed a clinical predictor of declining kidney function or cardiovascular outcomes.