Relation of atherogenic lipoproteins with estimated glomerular filtration rate decline: a longitudinal study

BACKGROUND Chronic kidney disease (CKD) is associated with dyslipidemia, but the role of atherogenic lipid fractions in CKD progression remains unclear. Here we assess whether baseline plasma levels of lipoprotein(a) [Lp(a)] and apolipoprotein C-III (apoC-III), causal cardiovascular (CV) risk factors being studied as therapeutic targets, are associated with decreasing estimated glomerular filtration rate (eGFR) over time. METHODS In the Penn Diabetes Heart Study (PDHS), a single-center observational cohort of type 2 diabetes patients without clinical CV disease or pre-existing CKD, we performed linear mixed effects modeling with incremental multivariable analysis to evaluate the effects of baseline plasma Lp(a) and apoC-III on the slope of eGFR over time for subjects with longitudinal data (N = 400). RESULTS Each two-fold higher plasma Lp(a) level was associated with an additional decline in eGFR by 0.50 mL/min/year in the fully adjusted model (p < 0.001). Baseline Lp(a) levels greater than the atherogenic cut-point of 30 mg/dL were associated with a decline in eGFR by 2.75 mL/min/year compared to 1.01 mL/min/year in subjects with baseline Lp(a) less than 30 mg/dL (p < 0.001). Although each two-fold higher apoC-III level was also associated with statistically significant decline in eGFR over time, as expected the association was attenuated after adjusting for baseline triglycerides, the key lipid intermediary regulated by apoC-III in circulation. CONCLUSIONS Elevated baseline plasma Lp(a) levels are associated with a decrease in eGFR over time independent of race, lipid medication use, and albuminuria, whereas elevated baseline apoC-III levels are associated with eGFR decline in a triglyceride-dependent fashion.