title: Relation of atherogenic lipoproteins with estimated glomerular filtration rate decline: a longitudinal study.
abstract: 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.
authors.affiliation: Renal 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.
authors.forename: Jennie
authors.initials: J
authors.lastname: Lin
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. sumeet.khetarpal@gmail.com.
authors.forename: Sumeet A
authors.initials: SA
authors.lastname: Khetarpal
authors.affiliation: Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. kterembu@mail.med.upenn.edu.
authors.forename: Karen
authors.initials: K
authors.lastname: Terembula
authors.affiliation: Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. muredach@mail.med.upenn.edu.
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.affiliation: Section of Nephrology, Department of Medicine, Yale School of Medicine, Program of Applied Translational Research, Yale University, New Haven, USA. francis.p.wilson@yale.edu.
authors.forename: F Perry
authors.initials: FP
authors.lastname: Wilson
mesh_terms: D053305:Apolipoprotein C-III / Q000097:blood*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
chemical_list: D053305:Apolipoprotein C-III; D017270:Lipoprotein(a); D014280:Triglycerides