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Relation of atherogenic lipoproteins with estimated glomerular filtration rate decline: a longitudinal study
Jennie Lin1, Sumeet A Khetarpal2, Karen Terembula3
1Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 1 Founders, 3400 Spruce Street, Philadelphia, PA, 19104, USA. linjenn@mail.med.upenn.edu.
Insights
High lipoprotein(a) [Lp(a)] levels significantly predict chronic kidney disease (CKD) progression. Apolipoprotein C-III (apoC-III) also impacts kidney function decline, but this effect is linked to triglyceride levels.
Area of Science:
- Nephrology
- Cardiology
- Metabolic Diseases
Background:
- Chronic kidney disease (CKD) is linked to dyslipidemia, but the specific role of atherogenic lipids in CKD progression is not fully understood.
- Lipoprotein(a) [Lp(a)] and apolipoprotein C-III (apoC-III) are emerging cardiovascular risk factors and potential therapeutic targets.
Purpose of the Study:
- To investigate the association between baseline plasma levels of Lp(a) and apoC-III and the rate of estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes.
- To determine if these associations are independent of other risk factors for CKD progression.
Main Methods:
- Utilized data from the Penn Diabetes Heart Study (PDHS), a cohort of 400 type 2 diabetes patients without prior cardiovascular disease or CKD.
- Employed linear mixed-effects modeling with multivariable analysis to assess the impact of baseline Lp(a) and apoC-III on eGFR slope over time.
Main Results:
- Each two-fold increase in plasma Lp(a) was associated with a 0.50 mL/min/year greater decline in eGFR (p < 0.001).
- Lp(a) levels above 30 mg/dL correlated with a significantly faster eGFR decline (2.75 mL/min/year) compared to lower levels (1.01 mL/min/year).
- Elevated apoC-III showed a statistically significant association with eGFR decline, which was attenuated after adjusting for triglycerides.
Conclusions:
- Elevated baseline Lp(a) is an independent predictor of eGFR decline in type 2 diabetes patients, irrespective of race, medication, or albuminuria.
- Elevated baseline apoC-III is associated with eGFR decline, but this relationship is dependent on triglyceride levels.
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.
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