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Do HDL and LDL subfractions play a role in atherosclerosis in end-stage renal disease (ESRD) patients?

  • Nephrology - Original Paper
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Abstract

Background

Significantly increased cardiovascular mortality in patients with chronic kidney (CKD) disease cannot be explained by traditional risk factors. Recent studies revealed that the quality of HDL and LDL cholesterol may be more important than their serum levels. The aim of this study was to assess which LDL and HDL subfractions were more abundant in end-stage renal disease (ESRD) patients and to analyse whether subfraction distribution could be associated with accelerated atherosclerotic processes.

Methods

This study included 50 ESRD patients undergoing dialysis and 20 healthy volunteers. LDL and HDL subfractions were analysed in serum with the use of Lipoprint system. All patients had intima-media thickness (IMT) measured.

Results

Statistically significant differences in subfractions between control and study group were observed in case of: HDL1 (p < 0.0001), HDL2 (p = 0.009), HDL3 (p < 0.0001), HDL4 (p = 0.003), HDL5 (p = 0.01), HDL7 (p < 0.0001), HDL8 (p < 0.0001), HDL9 (p < 0.0001), HDL10 (p < 0.0001), large HDL (p < 0.0001), HDL Small (p < 0.0001) as well as IDL-B (p = 0.014), IDLA (p = 0.011), LDL2 (p = 0.007). Significant differences were also observed in HDL and LDL subfraction distribution between haemodialysis patients with normal and increased IMT: HDL6 (p = 0.020), HDL Large (HDL1-3) (p = 0.017), HDL Intermediate (HDL4-7) (p = 0.017).

Conclusions

This study revealed that ESRD influenced HDL subfractions. In HD patients, large HDL subfractions are more abundant while small HDL fraction is more frequent in healthy persons. It failed to show the influence of end-stage disease on LDL subfraction levels. Shift in HDL subfractions might be responsible for the increased risk of atherosclerosis in CKD patients.

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References

  1. Navab KD, Elboudwarej O, Gharif M, Yu J, Hama SY, Safarpour S et al (2011) Chronic inflammatory disorders and accelerated atherosclerosis: chronic kidney disease. Curr Pharm Des 17(1):17–20

    Article  CAS  PubMed  Google Scholar 

  2. Kon V, Yang H, Fazio S (2015) Residual cardiovascular risk in chronic kidney disease: role of high-density lipoprotein. Arch Med Res 46:379–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. McCullough PA, Li S, Jurkovitz CT et al (2008) Chronic kidney disease, prevalence of premature cardiovascular disease, and relationship to short-term mortality. Am Heart J 156:277–283

    Article  PubMed  Google Scholar 

  4. Suganuma E, Zuo Y, Ayabe N et al (2006) Antiatherogenic effects of angiotensin receptor antagonism in mild renal dysfunction. J Am Soc Nephrol 17:433–441

    Article  CAS  PubMed  Google Scholar 

  5. Kaysen GA (2009) Lipid and lipoprotein metabolism in chronic kidney disease. J Ren Nutr 19:73–77

    Article  CAS  PubMed  Google Scholar 

  6. Matsushita K, van der Velde M, Chronic Kidney Disease Prognosis Consortium et al (2010) Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 375:2073–2081

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wanner C, Krane V, Marz W et al (2005) Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 353:238–248

    Article  CAS  PubMed  Google Scholar 

  8. Kones R (2013) Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes. Vasc Health Risk Manag 9:617–670

    Article  PubMed  PubMed Central  Google Scholar 

  9. Palmer SC, Navaneethan SD, Craig JC et al (2014) HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev 5:CD007784

    Google Scholar 

  10. Homma K, Homma Y, Shiina Y, Wakino S, Suzuki M, Fujishima S et al (2013) Skew of plasma low- and high-density lipoprotein distributions to less dense subfractions in normotriglyceridemic chronic kidney disease patients on maintenance hemodialysis treatment. Nephron Clin Pract 123(1–2):41–45

    Article  CAS  PubMed  Google Scholar 

  11. Griffin BA, Freeman DJ, Tait GW, Thompson J, Caslake MJ, Packard C et al (1994) Role of plasma triglyceride in the regulation of plasma low-density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk. Atherosclerosis 106:241–253

    Article  CAS  PubMed  Google Scholar 

  12. Hirano T, Ito Y, Koba S, Toyoda M, Ikejiri A, Saegusa H et al (2004) Clinical significance of small dense low-density lipoprotein cholesterol levels determined by the simple precipitation method. Arterioscler Thromb Vasc Biol 24:558–563

    Article  CAS  PubMed  Google Scholar 

  13. Homma Y, Michishita I, Hayashi H, Shigematsu H, Kanagawa Lipid Research Group (2010) Effects of low-dose simvastatin on the distribution of plasma cholesterol and oxidized low-density lipoprotein in three ultracentrifugally separated low-density lipoprotein subfractions: 12-month, open-label trial. J Atheroscler Thromb 17:1049–1053

    Article  CAS  PubMed  Google Scholar 

  14. Kaseda R, Jabs K, Hunley TE, Jones D, Bian A, Allen RM et al (2015) Dysfunctional high-density lipoproteins in children with chronic kidney disease. Metabolism 64(2):263–273

    Article  CAS  PubMed  Google Scholar 

  15. Holzer M, Birner-Gruenberger R, Stojakovic T, El-Gamal D, Binder V, Wadsack C et al (2011) Uremia alters HDL composition and function. J Am Soc Nephrol 22(9):1631–1641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tölle M, Huang T, Schuchardt M, Jankowski V, Prüfer N, Jankowski J et al (2012) High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A. Cardiovasc Res 94(1):154–162

    Article  PubMed  Google Scholar 

  17. Yamamoto S, Yancey PG, Ikizler TA, Jerome WG, Kaseda R, Cox B et al (2012) Dysfunctional high-density lipoprotein in patients on chronic hemodialysis. J Am Coll Cardiol 60(23):2372–2379

    Article  CAS  PubMed  Google Scholar 

  18. Maugeais C, Perez A, von der Mark E, Magg C, Pflieger P, Niesor EJ (2013) Evidence for a role of CETP in HDL remodeling and cholesterol efflux: role of cysteine 13 of CETP. Biochim Biophys Acta 1831(11):1644–1650

    Article  CAS  PubMed  Google Scholar 

  19. Rysz J, Gluba A, Fliser D, Speer T, Wiecek A (2014) Chronic kidney disease—different role for HDL? Curr Med Chem 21(25):2910–2916

    Article  Google Scholar 

  20. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M (2007) Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 115:459–467

    Article  PubMed  Google Scholar 

  21. Shimizu M, Furusyo N, Mitsumoto F, Takayama K, Ura K, Hiramine S et al (2015) Subclinical carotid atherosclerosis and triglycerides predict the incidence of chronic kidney disease in the Japanese general population: results from the Kyushu and Okinawa Population Study (KOPS). Atherosclerosis 238(2):207–212

    Article  CAS  PubMed  Google Scholar 

  22. Chonchol M, Gnahn H, Sander D (2008) Impact of subclinical carotid atherosclerosis on incident chronic kidney disease in the elderly. Nephrol Dial Transpl 23:2593–2598

    Article  Google Scholar 

  23. Dukát A, Oravec S, Wawruch M, Gavorník P, Sabaka P (2011) The incidence of dyslipidemia in a sample of asymptomatic probands established by the means of Lipoprint system]. Vnitr Lek 57(3):258–260

    PubMed  Google Scholar 

  24. Simova I (2015) Intima-media thickness: Appropriate evaluation and proper measurement, described. E-J ESC Counc Cardiol Pract 13(21). http://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-13/Intima-media-thickness-Appropriate-evaluation-and-proper-measurement-described

  25. Moradi H, Vaziri ND, Said HM, Kalantar-Zadeh K (2013) Role of HDL dysfunction in end-stage renal disease: a double-edged sword. J Ren Nutr. 23(3):203–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Vaziri ND, Navab K, Gollapudi P, Moradi H, Pahl MV, Barton CH, Fogelman AM, Navab M (2011) Salutary effects of hemodialysis on low-density lipoprotein proinflammatory and high-density lipoprotein anti-inflammatory properties in patient with end-stage renal disease. J Natl Med Assoc 103(6):524–533

    Article  PubMed  PubMed Central  Google Scholar 

  27. Stack AG, Bloembergen WE (2001) Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol 12(7):1516–1523

    CAS  PubMed  Google Scholar 

  28. Rysz J, Stolarek RA, Pedzik A, Nowicki M, Nowak D (2010) Serum antioxidant capacity is preserved in peritoneal dialysis contrary to its robust depletion after hemodialysis and hemodiafiltration sessions. Ther Apher Dial 14(2):209–217

    Article  CAS  PubMed  Google Scholar 

  29. Rysz J, Potargowicz E, Banach M, Luczyńska M, Stolarek R, Białasiewicz P et al (2006) Increased whole blood chemiluminescence in patients with chronic renal failure independent of hemodialysis treatment. Arch Immunol Ther Exp (Warsz) 54(5):347–355

    Article  Google Scholar 

  30. Maeda S, Nakanishi S, Yoneda M, Awaya T, Yamane K, Hirano T et al (2012) Associations between small dense LDL, HDL subfractions (HDL2, HDL3) and risk of atherosclerosis in Japanese-Americans. J Atheroscler Thromb 19(5):444–452

    Article  CAS  PubMed  Google Scholar 

  31. Bjornheded T, Babyi A, Bodjers G, Wiklund O (1996) Accumulation of lipoprotein fractions and subfractions in the arterial wall, determined in an in vitro perfusion system. Atherosclerosis 123:43–56

    Article  Google Scholar 

  32. Berneis KK, Krauss RM (2002) Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 43:1363–1379

    Article  CAS  PubMed  Google Scholar 

  33. Salonen JT, Salonen R, Seppanen K, Rauramaa R, Tuomilehto J (1991) HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction: a prospective study in eastern Finnish men. Circulation 84:129–139

    Article  CAS  PubMed  Google Scholar 

  34. Smuts CM, Weich HF, Weight MJ, Faber M, Kruger M, Lombard CJ et al (1994) Free cholesterol concentrations in the high-density lipoprotein subfraction-3 as a risk indicator in patients with angiographically documented coronary artery disease. Coron Artery Dis 5:331–338

    Article  CAS  PubMed  Google Scholar 

  35. Iwanejko J, Kwasniak M, Wybranska I, Hartwich J, Guevara I, Zdzienicka A et al (1996) Heterogeneity of high-density lipoprotein particles and insulin output during oral glucose tolerance test in men with coronary artery disease. Acta Diabetol 33:58–61

    Article  CAS  PubMed  Google Scholar 

  36. Tsuzaki K, Kotani K, Sano Y, Fujiwara S, Gazi IF, Elisaf M et al (2012) The relationship between adiponectin, an adiponectin gene polymorphism, and high-density lipoprotein particle size: from the Mima study. Metabolism 61(1):17–21

    Article  CAS  PubMed  Google Scholar 

  37. Eisenberg S (1984) High density lipoprotein metabolism. J Lipid Res 25(10):1017–1058

    CAS  PubMed  Google Scholar 

  38. Yamashita S, Ishigami M, Arai T, Sakai N, Hirano K, Kameda-Takemura K et al (1995) Very high density lipoproteins induced by plasma cholesteryl ester transfer protein CETP have a potent antiatherogenic function. Ann NY Acad Sci 748:606–608

    Article  CAS  PubMed  Google Scholar 

  39. Kontush A, Chantepie S, Chapman MJ (2003) Small, dense HDL particles exert potent protection of atherogenic LDL against oxidative stress. Arterioscler Thromb Vasc Biol 23:1881–1888

    Article  CAS  PubMed  Google Scholar 

  40. Favari E, Calabresi L, Adorni MP, Jessup W, Simonelli S, Franceschini G, Bernini F (2009) Small discoidal pre-beta1 HDL particles are efficient acceptors of cell cholesterol via ABCA1 and ABCG1. Biochemistry 48:11067–11074

    Article  CAS  PubMed  Google Scholar 

  41. de Souza JA, Vindis C, Nègre-Salvayre A, Rye KA, Couturier M, Therond P, Chantepie S, Salvayre R, Chapman MJ, Kontush A (2010) Small, dense HDL 3 particles attenuate apoptosis in endothelial cells: pivotal role of apolipo-protein A-I. J Cell Mol Med 14:608–620

    PubMed  Google Scholar 

  42. Camont L, Lhomme M, Rached F, Le Goff W, Nègre-Salvayre A, Salvayre R, Calzada C, Lagarde M, Chapman MJ, Kontush A (2013) Small, dense high-density lipoprotein-3 particles are enriched in negatively charged phospholipids relevance to cellular cholesterol efflux, antioxidative, antithrombotic, anti-inflammatory, and antiapoptotic functionalities. Arterioscler Thromb Vasc Biol 33:2715–2723

    Article  CAS  PubMed  Google Scholar 

  43. Bjornheden T, Babyi A, Bondjers G, Wiklund O (1996) Accumulation of lipoprotein fractions and subfractions in the arterial wall, determined in an in vitro perfusion system. Atherosclerosis 123:43–56

    Article  CAS  PubMed  Google Scholar 

  44. Galeano NF, Al-Haideri M, Keyserman F, Rumsey SC, Deckelbaum RJ (1998) Small dense low density lipoprotein has increased affinity for LDL receptor-independent cell surface binding sites: a potential mechanism for increased atherogenicity. J Lipid Res 39:1263–1273

    CAS  PubMed  Google Scholar 

  45. Tribble DL, Rizzo M, Chait A, Lewis DM, Blanche PJ, Krauss RM (2001) Enhanced oxidative susceptibility and reduced antioxidant content of metabolic precursors of small, dense low-density lipoproteins. Am J Med 110:103–110

    Article  CAS  PubMed  Google Scholar 

  46. Touboul PJ, Labreuche J, Bruckert E, Schargrodsky H, Prati P, Tosetto A et al (2014) HDL-C, triglycerides and carotid IMT: a meta-analysis of 21,000 patients with automated edge detection IMT measurement. Atherosclerosis 232(1):65–71

    Article  CAS  PubMed  Google Scholar 

  47. Kaseda R, Jabs K, Hunley TE, Jones D, Bian A, Allen RM et al (2015) Dysfunctional high-density lipoproteins in children with chronic kidney disease. Metabolism 64(2):263–273

    Article  CAS  PubMed  Google Scholar 

  48. Moradi H, Streja E, Kashyap ML, Vaziri ND, Fonarow GC, Kalantar-Zadeh K (2014) Elevated high-density lipoprotein cholesterol and cardiovascular mortality in maintenance hemodialysis patients. Nephrol Dial Transplant 29(8):1554–1562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Vaziri ND, Navab M, Fogelman AM (2010) HDL metabolism and activity in chronic kidney disease. Nat Rev Nephrol 6(5):287–296

    Article  CAS  PubMed  Google Scholar 

  50. Rysz J, Majewska E, Stolarek RA, Banach M, Ciałkowska-Rysz A, Baj Z (2006) Increased levels of soluble TNF-alpha receptors and cellular adhesion molecules in patients undergoing bioincompatible hemodialysis. Am J Nephrol 26(5):437–444

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Marek Nocuń was responsible for the statistical analysis of data. Three authors are (partially) supported by the Healthy Ageing Research Centre project (REGPOT-2012-2013-1, 7FP).

Authors’ contribution

Anna Gluba-Brzózka enrolled patients, carried out analysis of LDL and HDL subfractions, prepared database, and wrote the article; Beata Franczyk enrolled patients and performed echocardiographic examination; Maciej Banach participated in the design of the study; Magdalena Rysz-Górzyńska prepared database and participated in the design of the study. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Nephrology, Hypertension and Family Medicine, WAM University Hospital of Lodz, Zeromskiego 113, 90-549, Lodz, Poland

    Anna Gluba-Brzózka & Magdalena Rysz-Górzyńska

  2. Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Lodz, Poland

    Beata Franczyk

  3. Department of Hypertension, Medical University of Lodz, Lodz, Poland

    Maciej Banach & Magdalena Rysz-Górzyńska

  4. Healthy Aging Research Center, Medical University of Lodz, Lodz, Poland

    Anna Gluba-Brzózka & Maciej Banach

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  1. Anna Gluba-Brzózka
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  2. Beata Franczyk
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  4. Magdalena Rysz-Górzyńska
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Correspondence to Anna Gluba-Brzózka.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study.

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Gluba-Brzózka, A., Franczyk, B., Banach, M. et al. Do HDL and LDL subfractions play a role in atherosclerosis in end-stage renal disease (ESRD) patients?. Int Urol Nephrol 49, 155–164 (2017). https://doi.org/10.1007/s11255-016-1466-x

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  • DOI: https://doi.org/10.1007/s11255-016-1466-x

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