Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). One of the most important pathophysiological mechanisms for CVD in patients with CKD is the widespread and possibly accelerated formation of atherosclerotic plaques due to hyperlipidemia, uremic toxins, inflammation, oxidative stress, and endothelial dysfunction. Recent studies showed that the level of oxidized low-density lipoprotein cholesterol increases, and that high--density lipoprotein cholesterol dysfunction occurs as kidney function declines and inflammation becomes more prevalent. In this review, we aimed to discuss the effect of kidney dysfunction, oxidative stress, and inflammation on lipid -profile.

Keywords:
Hyperlipidemia, Oxidized low-density lipoprotein, Chronic kidney disease
1.
Vaziri ND: Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential consequences. Am J Physiol Renal Physiol 2006; 290:F262–F272.
2.
Zoccali C, Vanholder R, Massy ZA, Ortiz A, Sarafidis P, Dekker FW, et al: The systemic nature of CKD. Nat Rev Nephrol 2017; 13: 344–358.
3.
Vlagopoulos PT, Sarnak MJ: Traditional and nontraditional cardiovascular risk factors in chronic kidney disease. Med Clin North Am 2005; 89: 587–611.
4.
Kendrick J, Chonchol MB: Nontraditional risk factors for cardiovascular disease in patients with chronic kidney disease. Nat Clin Pract Nephrol 2008; 4: 672–681.
5.
Kanbay M, Vervloet M, Cozzolino M, Siriopol D, Covic A, Goldsmith D, et al: Novel faces of fibroblast growth factor 23 (FGF23): iron deficiency, inflammation, insulin resistance, left ventricular hypertrophy, proteinuria and acute kidney injury. Calcif Tissue Int 2017; 100: 217–228.
6.
Kanbay M, Solak Y, Siriopol D, Aslan G, Afsar B, Yazici D, et al: Sclerostin, cardiovascular disease and mortality: a systematic review and meta-analysis. Int Urol Nephrol 2016; 48: 2029–2042.
7.
Yilmaz MI, Siriopol D, Saglam M, Unal HU, Karaman M, Gezer M, et al: Osteoprotegerin in chronic kidney disease: associations with vascular damage and cardiovascular events. Calcif Tissue Int 2016; 99: 121–130.
8.
Afsar B, Yilmaz MI, Siriopol D, Unal HU, Saglam M, Karaman M, et al: Thyroid function and cardiovascular events in chronic kidney disease patients. J Nephrol 2017; 30: 235–242.
9.
Moradi H, Vaziri ND, Kashyap ML, Said HM, Kalantar-Zadeh K: Role of HDL dysfunction in end-stage renal disease: a double-edged sword. J Ren Nutr 2013; 23: 203–206.
10.
Kanbay M, Afsar B, Siriopol D, Unal HU, Karaman M, Saglam M, et al: Endostatin in chronic kidney disease: associations with inflammation, vascular abnormalities, cardiovascular events and survival. Eur J Intern Med 2016; 33: 81–87.
11.
Vaziri ND: Role of dyslipidemia in impairment of energy metabolism, oxidative stress, inflammation and cardiovascular disease in chronic kidney disease. Clin Exp Nephrol 2014; 18: 265–268.
12.
Cohen DE, Fisher EA: Lipoprotein metabolism, dyslipidemia, and nonalcoholic fatty liver disease. Semin Liver Dis 2013; 33: 380–388.
13.
Moradi H, Pahl MV, Elahimehr R, Vaziri ND: Impaired antioxidant activity of high-density lipoprotein in chronic kidney disease. Transl Res 2009; 153: 77–85.
14.
Vaziri ND, Liang K, Parks JS: Down-regulation of hepatic lecithin:cholesterol acyltransferase gene expression in chronic renal failure. Kidney Int 2001; 59: 2192–2196.
15.
Ribeiro S, Faria Mdo S, Silva G, Nascimento H, Rocha-Pereira P, Miranda V, et al: Oxidized low-density lipoprotein and lipoprotein(a) levels in chronic kidney disease patients under hemodialysis: influence of adiponectin and of a polymorphism in the apolipoprotein(a) gene. Hemodial Int 2012; 16: 481–490.
16.
Agrawal S, Zaritsky JJ, Fornoni A, Smoyer WE: Dyslipidaemia in nephrotic syndrome: mechanisms and treatment. Nat Rev Nephrol 2018; 14: 57–70.
17.
Vaziri ND: Disorders of lipid metabolism in nephrotic syndrome: mechanisms and consequences. Kidney Int 2016; 90: 41–52.
18.
Joven J, Villabona C, Vilella E, Masana L, Alberti R, Valles M: Abnormalities of lipoprotein metabolism in patients with the nephrotic syndrome. N Engl J Med 1990; 323: 579–584.
19.
Zewinger S, Speer T, Kleber ME, Scharnagl H, Woitas R, Lepper PM, et al: HDL cholesterol is not associated with lower mortality in patients with kidney dysfunction. J Am Soc Nephrol 2014; 25: 1073–1082.
20.
Imhof BA, Aurrand-Lions M: Adhesion mechanisms regulating the migration of monocytes. Nat Rev Immunol 2004; 4: 432–444.
21.
Kanbay M, Solak Y, Unal HU, Kurt YG, Gok M, Cetinkaya H, et al: Monocyte count/HDL cholesterol ratio and cardiovascular events in patients with chronic kidney disease. Int Urol Nephrol 2014; 46: 1619–1625.
22.
Vaziri ND: HDL abnormalities in nephrotic syndrome and chronic kidney disease. Nat Rev Nephrol 2016; 12: 37–47.
23.
Han S, Vaziri ND, Gollapudi P, Kwok V, Moradi H: Hepatic fatty acid and cholesterol metabolism in nephrotic syndrome. Am J Transl Res 2013; 5: 246–253.
24.
Kwan BC, Kronenberg F, Beddhu S, Cheung AK: Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol 2007; 18: 1246–1261.
25.
Quaschning T, Krane V, Metzger T, Wanner C: Abnormalities in uremic lipoprotein metabolism and its impact on cardiovascular disease. Am J Kidney Dis 2001; 38(4 suppl 1):S14–S19.
26.
Nitta K: Clinical assessment and management of dyslipidemia in patients with chronic kidney disease. Clin Exp Nephrol 2012; 16: 522–529.
27.
Kopple JD: The phenomenon of altered risk factor patterns or reverse epidemiology in persons with advanced chronic kidney failure. Am J Clin Nutr 2005; 81: 1257–1266.
28.
Tsirpanlis G, Boufidou F, Zoga M, Triantafyllis G, Fatourou A, Stamatelou K, et al: Low cholesterol along with inflammation predicts morbidity and mortality in hemodialysis patients. Hemodial Int 2009; 13: 197–204.
29.
De Nicola L, Provenzano M, Chiodini P, D’Arrigo G, Tripepi G, Del Vecchio L, et al: Prognostic role of LDL cholesterol in non-dialysis chronic kidney disease: multicenter prospective study in Italy. Nutr Metab Cardiovasc Dis 2015; 25: 756–762.
30.
Storey BC, Staplin N, Haynes R, Reith C, Emberson J, Herrington WG, et al: Lowering LDL cholesterol reduces cardiovascular risk independently of presence of inflammation. Kidney Int 2017; 93: 1000–1007.
31.
Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C: Oxidative stress in end-stage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant 2003; 18: 1272–1280.
32.
Vaziri ND: Oxidative stress in uremia: nature, mechanisms, and potential consequences. Semin Nephrol 2004; 24: 469–473.
33.
Teng F, Zhu R, Zou C, Xue Y, Yang M, Song H, et al: Interaction between serum uric acid and triglycerides in relation to blood pressure. J Hum Hypertens 2011; 25: 686–691.
34.
Peng TC, Wang CC, Kao TW, Chan JY, Yang YH, Chang YW, et al: Relationship between hyperuricemia and lipid profiles in US adults. Biomed Res Int 2015; 2015: 127596.
35.
Berkowitz D: Blood lipid and uric acid interrelationships. JAMA 1964; 190: 856–858.
36.
Kuwabara M, Borghi C, Cicero AF, Hisatome I, Niwa K, Ohno M, Johnson RJ, Lanaspa MA: Elevated serum uric acid increases risks for developing high LDL cholesterol and hypertriglyceridemia: a five-year cohort study in Japan. Int J Cardiol 2018;pii:S0167-5273(17)37927-5.
37.
Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al: 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am College Cardiol 2014; 63(25 Pt B):2889–2934.
38.
Zhao YY, Vaziri ND, Lin RC: Lipidomics: new insight into kidney disease. Adv Clin Chem 2015; 68: 153–175.
39.
Chen H, Chen L, Liu D, Chen DQ, Vaziri ND, Yu XY, et al: Combined clinical phenotype and lipidomic analysis reveals the impact of chronic kidney disease on lipid metabolism. J Proteome Res 2017; 16: 1566–1578.
40.
Reis A, Rudnitskaya A, Chariyavilaskul P, Dhaun N, Melville V, Goddard J, et al: Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease. J Lipid Res 2015; 56: 413–422.
41.
de Gomez Dumm NT, Giammona AM, Touceda LA, Raimondi C: Lipid abnormalities in chronic renal failure patients undergoing hemodialysis. Medicina (B Aires) 2001; 61: 142–146.
42.
Bergeron N, Phan BA, Ding Y, Fong A, Krauss RM: Proprotein convertase subtilisin/kexin type 9 inhibition: a new therapeutic mechanism for reducing cardiovascular disease risk. Circulation 2015; 132: 1648–1666.
43.
Nozue T: Lipid lowering therapy and circulating PCSK9 concentration. J Atheroscler Thromb 2017; 24: 895–907.
44.
Fisher TS, Lo Surdo P, Pandit S, Mattu M, Santoro JC, Wisniewski D, et al: Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation. J Biol Chem 2007; 282: 20502–20512.
45.
Seidah NG, Awan Z, Chretien M, Mbikay M: PCSK9: a key modulator of cardiovascular health. Circ Res 2014; 114: 1022–1036.
46.
Abujrad H, Mayne J, Ruzicka M, Cousins M, Raymond A, Cheesman J, et al: Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels. Atherosclerosis 2014; 233: 123–129.
47.
Rogacev KS, Heine GH, Silbernagel G, Kleber ME, Seiler S, Emrich I, et al: PCSK9 plasma concentrations are independent of GFR and do not predict cardiovascular events in patients with decreased GFR. PLoS One 2016; 11:e0146920.
48.
Pavlakou P, Liberopoulos E, Dounousi E, Elisaf M: PCSK9 in chronic kidney disease. Int Urol Nephrol 2017; 49: 1015–1024.
49.
Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, et al: Reductions in atherogenic lipids and major cardiovascular events: a pooled analysis of 10 ODYSSEY trials comparing alirocumab with control. Circulation 2016; 134: 1931–1943.
50.
Bonaca MP, Nault P, Giugliano RP, Keech AC, Pineda AL, Kanevsky E, et al: Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease: insights from the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Circulation 2017; 137: 338–350.
51.
Zheng-Lin B, Ortiz A: Lipid management in chronic kidney disease: systematic review of PCSK9 targeting. Drugs 2018; 78: 215–229.
52.
Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al: The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011; 377: 2181–2192.
53.
Kaysen GA: Lipid-lowering therapy in CKD: should we use it and in which patients. Blood Purif 2017; 43: 196–199.
54.
Goicoechea M, de Vinuesa SG, Lahera V, Cachofeiro V, Gomez-Campdera F, Vega A, et al: Effects of atorvastatin on inflammatory and fibrinolytic parameters in patients with chronic kidney disease. J Am Soc Nephrol 2006; 17(12 suppl 3):S231–S235.
55.
Kanbay M, Yildirir A, Bozbas H, Ulus T, Bilgi M, Muderrisoglu H, et al: Statin therapy helps to control blood pressure levels in hypertensive dyslipidemic patients. Ren Fail 2005; 27: 297–303.
56.
Wanner C, Krane V, Marz W, Olschewski M, Mann JF, Ruf G, et al: Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005; 353: 238–248.
57.
Kanbay M, Turgut F, Covic A, Goldsmith D: Statin treatment for dyslipidemia in chronic kidney disease and renal transplantation: a review of the evidence. J Nephrol 2009; 22: 598–609.
58.
Tonelli M, Moye L, Sacks FM, Cole T, Curhan GC: Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease. J Am Soc Nephrol 2003; 14: 1605–1613.
59.
Bianchi S, Bigazzi R, Caiazza A, Campese VM: A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease. Am J Kidney Dis 2003; 41: 565–570.
60.
Weiner DE, Sarnak MJ: Managing dyslipidemia in chronic kidney disease. J Gen Intern Med 2004; 19: 1045–1052.
61.
Seliger SL, Weiss NS, Gillen DL, Kestenbaum B, Ball A, Sherrard DJ, et al: HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients. Kidney Int 2002; 61: 297–304.
62.
Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, et al: Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet 2000; 356: 1213–1218.
63.
Islam KN, O’Byrne D, Devaraj S, Palmer B, Grundy SM, Jialal I: Alpha-tocopherol supplementation decreases the oxidative susceptibility of LDL in renal failure patients on dialysis therapy. Atherosclerosis 2000; 150: 217–224.
64.
Daud ZA, Tubie B, Sheyman M, Osia R, Adams J, Tubie S, et al: Vitamin E tocotrienol supplementation improves lipid profiles in chronic hemodialysis patients. Vasc Health Risk Manag 2013; 9: 747–761.
65.
Bolignano D, Cernaro V, Gembillo G, Baggetta R, Buemi M, D’Arrigo G: Antioxidant agents for delaying diabetic kidney ­disease progression: a systematic review and meta-analysis. PLoS One 2017; 12:e0178699.
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2018
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