Skip to main content
Top
Published in: BMC Nephrology 1/2015

Open Access 01-12-2015 | Research article

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

Authors: Jennie Lin, Sumeet A. Khetarpal, Karen Terembula, Muredach P. Reilly, F. Perry Wilson

Published in: BMC Nephrology | Issue 1/2015

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sarnak MJ. Kidney Disease as a Risk Factor for Development of Cardiovascular Disease: A Statement From the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108:2154–69. doi:10.1161/01.CIR.0000095676.90936.80.CrossRefPubMed Sarnak MJ. Kidney Disease as a Risk Factor for Development of Cardiovascular Disease: A Statement From the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108:2154–69. doi:10.​1161/​01.​CIR.​0000095676.​90936.​80.CrossRefPubMed
3.
go back to reference Manjunath G, Tighiouart H, Ibrahim H, MacLeod B, Salem DN, et al. Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community. J Am Coll Cardiol. 2003;41:47–55.CrossRefPubMed Manjunath G, Tighiouart H, Ibrahim H, MacLeod B, Salem DN, et al. Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community. J Am Coll Cardiol. 2003;41:47–55.CrossRefPubMed
7.
go back to reference Kronenberg F, Utermann G, Dieplinger H. Lipoprotein(a) in renal disease. Am J Kidney Dis. 1996;27:1–25.CrossRefPubMed Kronenberg F, Utermann G, Dieplinger H. Lipoprotein(a) in renal disease. Am J Kidney Dis. 1996;27:1–25.CrossRefPubMed
15.
go back to reference Samuelsson O, Mulec H, Knight-Gibson C, Attman PO, Kron B, et al. Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency. Nephrol Dial Transplant. 1997;12:1908–15.CrossRefPubMed Samuelsson O, Mulec H, Knight-Gibson C, Attman PO, Kron B, et al. Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency. Nephrol Dial Transplant. 1997;12:1908–15.CrossRefPubMed
16.
go back to reference Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA. 2002;287:2570–81.CrossRefPubMed Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA. 2002;287:2570–81.CrossRefPubMed
18.
go back to reference Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–34. doi:10.1056/NEJM199807233390404.CrossRefPubMed Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–34. doi:10.​1056/​NEJM199807233390​404.CrossRefPubMed
19.
go back to reference Koschinsky ML, Beisiegel U, Henne-Bruns D, Eaton DL, Lawn RM. Apolipoprotein(a) size heterogeneity is related to variable number of repeat sequences in its mRNA. Biochemistry. 1990;29:640–4.CrossRefPubMed Koschinsky ML, Beisiegel U, Henne-Bruns D, Eaton DL, Lawn RM. Apolipoprotein(a) size heterogeneity is related to variable number of repeat sequences in its mRNA. Biochemistry. 1990;29:640–4.CrossRefPubMed
23.
go back to reference The TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute (2014) Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease. N Engl J Med: 140624114120003. doi:10.1056/NEJMoa1307095 The TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute (2014) Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease. N Engl J Med: 140624114120003. doi:10.​1056/​NEJMoa1307095
24.
go back to reference Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, et al. (2013) Common variants associated with plasma triglycerides and risk for coronary artery disease. Nature Publishing Group 45: 1345–1352. doi:10.1038/ng.2795 Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, et al. (2013) Common variants associated with plasma triglycerides and risk for coronary artery disease. Nature Publishing Group 45: 1345–1352. doi:10.​1038/​ng.​2795
29.
go back to reference Mulvey CK, McNeill AM, Girman CJ, Churchill TW, Terembula K, et al. Differential Associations of Oral Glucose Tolerance Test-Derived Measures of Insulin Sensitivity and Pancreatic β-Cell Function With Coronary Artery Calcification and Microalbuminuria in Type 2 Diabetes. Diabetes Care. 2014;37:124–33. doi:10.2337/dc12-1880.CrossRefPubMed Mulvey CK, McNeill AM, Girman CJ, Churchill TW, Terembula K, et al. Differential Associations of Oral Glucose Tolerance Test-Derived Measures of Insulin Sensitivity and Pancreatic β-Cell Function With Coronary Artery Calcification and Microalbuminuria in Type 2 Diabetes. Diabetes Care. 2014;37:124–33. doi:10.​2337/​dc12-1880.CrossRefPubMed
30.
31.
go back to reference Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.CrossRefPubMed Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.CrossRefPubMed
32.
go back to reference Akaike H. A new look at the statistical model identification. IEEE Trans Autom Control. 1974;19:716–23.CrossRef Akaike H. A new look at the statistical model identification. IEEE Trans Autom Control. 1974;19:716–23.CrossRef
37.
go back to reference Kronenberg F, Trenkwalder E, Lingenhel A, Friedrich G, Lhotta K, et al. Renovascular arteriovenous differences in Lp[a] plasma concentrations suggest removal of Lp[a] from the renal circulation. J Lipid Res. 1997;38:1755–63.PubMed Kronenberg F, Trenkwalder E, Lingenhel A, Friedrich G, Lhotta K, et al. Renovascular arteriovenous differences in Lp[a] plasma concentrations suggest removal of Lp[a] from the renal circulation. J Lipid Res. 1997;38:1755–63.PubMed
42.
go back to reference Song K-H, Ko SH, Kim H-W, Ahn Y-B, Lee J-M, et al. Prospective study of lipoprotein(a) as a risk factor for deteriorating renal function in type 2 diabetic patients with overt proteinuria. Diabetes Care. 2005;28:1718–23.CrossRefPubMed Song K-H, Ko SH, Kim H-W, Ahn Y-B, Lee J-M, et al. Prospective study of lipoprotein(a) as a risk factor for deteriorating renal function in type 2 diabetic patients with overt proteinuria. Diabetes Care. 2005;28:1718–23.CrossRefPubMed
43.
go back to reference Rahman M, Yang W, Akkina S, Alper A, Anderson AH, et al. (2014) Relation of Serum Lipids and Lipoproteins with Progression of CKD: The CRIC Study. Clinical Journal of the American Society of Nephrology. doi:10.2215/CJN.09320913 Rahman M, Yang W, Akkina S, Alper A, Anderson AH, et al. (2014) Relation of Serum Lipids and Lipoproteins with Progression of CKD: The CRIC Study. Clinical Journal of the American Society of Nephrology. doi:10.​2215/​CJN.​09320913
44.
go back to reference Keane WF, Tomassini JE, Neff DR. Lipid abnormalities in patients with chronic kidney disease: implications for the pathophysiology of atherosclerosis. J Atheroscler Thromb. 2013;20:123–33.CrossRefPubMed Keane WF, Tomassini JE, Neff DR. Lipid abnormalities in patients with chronic kidney disease: implications for the pathophysiology of atherosclerosis. J Atheroscler Thromb. 2013;20:123–33.CrossRefPubMed
Metadata
Title
Relation of atherogenic lipoproteins with estimated glomerular filtration rate decline: a longitudinal study
Authors
Jennie Lin
Sumeet A. Khetarpal
Karen Terembula
Muredach P. Reilly
F. Perry Wilson
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2015
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-015-0122-5

Other articles of this Issue 1/2015

BMC Nephrology 1/2015 Go to the issue