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.
Highlights
Worldwide, chronic kidney disease (CKD) represents a high public health priority [1]
Vlad et al showed that lipoprotein(a) (Lp(a)), the genetic polymorphisms of apolipoprotein(a), apolipoprotein E (ApoE), and apolipoprotein B (ApoB) undergo modifications in uremic patients, being correlated with cardiovascular events [10]
It was pointed out that in end-stage renal disease (ESRD) patients, Lp(a) levels were independent risk factors for atherothrombosis and cardiovascular mortality, LMW apo(a) phenotype was the best predictor for coronary events, single nucleotide polymorphisms in ApoE gene increased the risk of cardiovascular events, and ApoB had a significant correlation with the value of carotid intima-media thickness and vascular stiffness [10]
Summary
Chronic kidney disease (CKD) represents a high public health priority [1]. Renal function parameters (GFR, creatinine, and BUN) were the most important determinants of serum ApoA-IV levels in patients with CKD [29]. Several clinical studies (e.g., AMORIS (Apolipoprotein-related MOrtality RISk) [38] or INTERHEART [39]) have shown that the ApoB/ApoA-I ratio is strongly correlated with cardiovascular events such as myocardial infarction and stroke [40]. PCSK9 is an enzyme accepted as a new biomarker for the lipid metabolism, a novel therapeutic target for hypercholesterolemia, because the inhibition of PCSK9 may be one of the options for lowering cardiovascular risk [47,48,49] It triggers the reduction of LDLR levels without affecting the LDLR mRNA (messenger ribonucleic acid). By activating the SREBP-2 pathway, statins increase the level of PCSK9, limiting the efficiency of these drugs for lowering LDL cholesterol [46]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
