Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec 14:2019:6906278.
doi: 10.1155/2019/6906278. eCollection 2019.

Apolipoproteins A and B and PCSK9: Nontraditional Cardiovascular Risk Factors in Chronic Kidney Disease and in End-Stage Renal Disease

Cristiana-Elena Vlad  1   2 , Liliana Foia  2 , Roxana Popescu  2 , Iuliu Ivanov  2 , Mihaela Catalina Luca  2 , Carmen Delianu  2 , Vasilica Toma  2 , Cristian Statescu  2 , Ciprian Rezus  2   3 , Laura Florea  1   2
Affiliations
Review

Apolipoproteins A and B and PCSK9: Nontraditional Cardiovascular Risk Factors in Chronic Kidney Disease and in End-Stage Renal Disease

Cristiana-Elena Vlad et al. J Diabetes Res. .

Abstract

Purpose: Nontraditional cardiovascular risk factors as apolipoprotein A (ApoA), apolipoprotein B (ApoB), and the proprotein convertase subtilisin/kexin type 9 (PCSK9) increase the prevalence of cardiovascular mortality in chronic kidney disease (CKD) or in end-stage renal disease (ESRD) through quantitative alterations. This review is aimed at establishing the biomarker (ApoA, ApoB, and PCSK9) level variations in uremic patients, to identify the studies showing the association between these biomarkers and the development of cardiovascular events and to depict the therapeutic options to reduce cardiovascular risk in CKD and ESRD patients.

Methods: We searched the electronic database of PubMed, Scopus, EBSCO, and Cochrane CENTRAL for studies evaluating apolipoproteins and PCSK9 in CKD and ESRD. Randomized controlled trials, observational studies (including case-control, prospective or retrospective cohort), and reviews/meta-analysis were included if reference was made to those keys and cardiovascular outcomes in CKD/ESRD.

Results: 18 studies met inclusion criteria. Serum ApoA-I has been significantly associated with the development of new cardiovascular event and with cardiovascular mortality in ESRD patients. ApoA-IV level was independently associated with maximum carotid intima-media thickness (cIMT) and was a predictor for sudden cardiac death. The ApoB/ApoA-I ratio represents a strong predictor for coronary artery calcifications, cardiovascular mortality, and myocardial infarction in CKD/ESRD. Plasma levels of PCSK9 were not associated with cardiovascular events in CKD patients.

Conclusions: Although the "dyslipidemic status" in CKD/ESRD is not clearly depicted, due to different research findings, ApoA-I, ApoA-IV, and ApoB/ApoA-I ratio could be predictors of cardiovascular risk. Serum PCSK9 levels were not associated with the cardiovascular events in patients with CKD/ESRD. Probably in the future, the treatment of dyslipidemia in CKD/ESRD will be aimed at discovering new effective therapies on the action of these biomarkers.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
The pathophysiology of atherosclerosis and arteriosclerosis in patients with CKD. CHD: coronary heart disease; CKD: chronic kidney disease; LV: left ventricle; MI: myocardial infarction.
Figure 2
Figure 2
The biological functions of ApoA-I. In the liver, ApoA-I initiates the biogenesis of HDL and the lipid uptake and promotes cholesterol efflux. In the vascular endothelium, it maintains endothelial cell homeostasis. ApoE: apolipoprotein E; ABCA1: ATP-binding cassette transporters; LCAT: lecithin-cholesterol acyltransferase; SR-BI: scavenger receptor class B type I.
Figure 3
Figure 3
The roles of ApoA-IV. ApoA-IV has antioxidant and antiatherogenic functions. ApoA-IV activates LCAT and modulates LPL activation, favoring cholesteryl ester transfer from HDL to LDL. LCAT: lecithin-cholesterol acyltransferase; LPL: lipoprotein lipase.
Figure 4
Figure 4
The roles of ApoB. In the liver, ApoB promotes the formation of nascent VLDL and also is essential for the linking of LDL particles to LDLR for cellular absorption and degradation of LDL particles. In the intestine, ApoB stimulates the formation of chylomicrons. LDL: low-density lipoprotein; VLDL: very low-density lipoprotein.
Figure 5
Figure 5
The biological functions of PCSK9. LDLR: low-density lipoprotein receptor; VLDLRs: very low-density lipoprotein receptors.
See this image and copyright information in PMC

References

    1. Ortiz A., Covic A., Fliser D., et al. Epidemiology, contributors to, and clinical trials of mortality risk in chronic kidney failure. The Lancet. 2014;383(9931):1831–1843. doi: 10.1016/S0140-6736(14)60384-6. - DOI - PubMed
    1. Eggers P. W. Has the incidence of end-stage renal disease in the USA and other countries stabilized? Current Opinion in Nephrology and Hypertension. 2011;20(3):241–245. doi: 10.1097/MNH.0b013e3283454319. - DOI - PubMed
    1. Couser W. G., Riella M. C. World Kidney Day 2011: protect your kidneys, save your heart. Nephron Clinical Practice. 2011;117(3):I–IV. doi: 10.1159/000323547. - DOI - PubMed
    1. Lozano R., Naghavi M., Foreman K., et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. The Lancet. 2012;380(9859):2095–2128. doi: 10.1016/S0140-6736(12)61728-0. - DOI - PMC - PubMed
    1. Vaziri N. D. Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential consequences. American Journal of Physiology. Renal Physiology. 2006;290(2):F262–F272. doi: 10.1152/ajprenal.00099.2005. - DOI - PubMed

MeSH terms