Abstract
BackgroundChronic 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.MethodsIn 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).ResultsEach 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.ConclusionsElevated 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0122-5) contains supplementary material, which is available to authorized users.
Highlights
Chronic kidney disease (CKD) is associated with dyslipidemia, but the role of atherogenic lipid fractions in CKD progression remains unclear
The median baseline estimated glomerular filtration rate (eGFR) was above 90 mL/min/1.73 m2, and the median urinary Albumin to creatinine ratio (ACR) was below 6 mg/g (Table 1)
In this study of individuals with type 2 diabetes mellitus (T2DM), we demonstrate that baseline plasma Lp(a) levels strongly associate with eGFR decline and that a significant more modest association exists between baseline plasma apoC-III levels and eGFR Decline
Summary
Chronic kidney disease (CKD) is associated with dyslipidemia, but the role of atherogenic lipid fractions in CKD progression remains unclear. Dyslipidemia in CKD is characterized by elevated levels of apolipoprotein C-III (apoC-III), an exchangeable apolipoprotein on lipoprotein particles that inhibits lipoprotein lipase, thereby reducing clearance of very-low-density-lipoproteins (VLDL) and the triglycerides (TGs) they carry [2, 9,10,11,12,13,14,15,16,17,18] Both Lp(a) and apoC-III levels have recently been identified as genetic causal risk factors for CV disease, [5,6,7, 19,20,21,22,23,24] but their role in CKD development and progression remain unclear. Aberrant concentrations of other lipid fractions are associated with CKD, we chose to focus on Lp(a) and
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