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Causes and consequences of lipoprotein(a) abnormalities in kidney disease

  • Review Article
  • WCN 2013 Satellite Symposium ‘‘Kidney and Lipids’’
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Lipoprotein(a) is one of the strongest genetically determined risk factors for cardiovascular disease, and patients with chronic kidney disease have major disturbances in lipoprotein(a) metabolism. Concentrations are increased and are influenced by glomerular filtration rate (GFR) and the amount of proteinuria. The reason for this elevation can be increased synthesis, as is the case for patients with nephrotic syndrome or those treated by peritoneal dialysis. In hemodialysis patients, a catabolic block is the reason for this elevation. The elevated concentrations might contribute to the tremendous cardiovascular risk in this particular population. In particular, the genetically determined small apolipoprotein(a) isoforms are associated with an increased risk for cardiovascular events and total mortality.

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References

  1. Kronenberg F, Utermann G. Lipoprotein(a)—resurrected by genetics. J Intern Med. 2013;273:6–30.

    Article  CAS  PubMed  Google Scholar 

  2. Utermann G, Menzel HJ, Kraft HG, Duba HC, Kemmler HG, Seitz C. Lp(a) glycoprotein phenotypes: inheritance and relation to Lp(a)-lipoprotein concentrations in plasma. J Clin Invest. 1987;80:458–65.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Erqou S, Kaptoge S, Perry PL, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302:412–23.

    Article  CAS  PubMed  Google Scholar 

  4. Sandholzer C, Saha N, Kark JD, et al. Apo(a) isoforms predict risk for coronary heart disease: a study in six populations. Arterioscler Thromb. 1992;12:1214–26.

    Article  CAS  PubMed  Google Scholar 

  5. Sandholzer C, Hallman DM, Saha N, et al. Effects of the apolipoprotein(a) size polymorphism on the lipoprotein(a) concentration in 7 ethnic groups. Hum Genet. 1991;86:607–14.

    Article  CAS  PubMed  Google Scholar 

  6. Kraft HG, Lingenhel A, Köchl S, et al. Apolipoprotein(a) Kringle IV repeat number predicts risk for coronary heart disease. Arterioscler Thromb Vasc Biol. 1996;16:713–9.

    Article  CAS  PubMed  Google Scholar 

  7. Erqou S, Thompson A, Di AE, et al. Apolipoprotein(a) isoforms and the risk of vascular disease: systematic review of 40 studies involving 58,000 participants. J Am Coll Cardiol. 2010;55:2160–7.

    Article  CAS  PubMed  Google Scholar 

  8. Bergmark C, Dewan A, Orsoni A, et al. A novel function of lipoprotein[a] as a preferential carrier of oxidized phospholipids in human plasma. J Lipid Res. 2008;49:2230–9.

    Article  CAS  PubMed  Google Scholar 

  9. Kiechl S, Willeit J, Mayr M, et al. Oxidized phospholipids, lipoprotein(a), lipoprotein-associated phospholipase A2 activity and 10-year cardiovascular outcomes: prospective results from the Bruneck study. Arterioscler Thromb Vasc Biol. 2007;27:1788–95.

    Article  CAS  PubMed  Google Scholar 

  10. Tsimikas S, Kiechl S, Willeit J, et al. Oxidized phospholipids predict the presence and progression of carotid and femoral atherosclerosis and symptomatic cardiovascular disease: five-year prospective results from the Bruneck Study. J Am Coll Cardiol. 2006;47:2219–28.

    Article  CAS  PubMed  Google Scholar 

  11. Tsimikas S, Mallat Z, Talmud PJ, et al. Oxidation-specific biomarkers, lipoprotein(a), and risk of fatal and nonfatal coronary events. J Am Coll Cardiol. 2010;56:946–55.

    Article  CAS  PubMed  Google Scholar 

  12. Tsimikas S, Witztum JL. The role of oxidized phospholipids in mediating lipoprotein(a) atherogenicity. Curr Opin Lipidol. 2008;19:369–77.

    Article  CAS  PubMed  Google Scholar 

  13. Kronenberg F, Trenkwalder E, Lingenhel A, 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.

    CAS  PubMed  Google Scholar 

  14. Mooser V, Marcovina SM, White AL, Hobbs HH. Kringle-containing fragments of apolipoprotein(a) circulate in human plasma and are excreted into the urine. J Clin Invest. 1996;98:2414–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Kostner KM, Maurer G, Huber K, et al. Urinary excretion of apo(a) fragments. Role in apo(a) catabolism. Arterioscler Thromb Vasc Biol. 1996;16:905–11.

    Article  CAS  PubMed  Google Scholar 

  16. Kronenberg F, Kuen E, Ritz E, et al. Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure. J Am Soc Nephrol. 2000;11:105–15.

    CAS  PubMed  Google Scholar 

  17. Dieplinger H, Lackner C, Kronenberg F, et al. Elevated plasma concentrations of lipoprotein(a) in patients with end-stage renal disease are not related to the size polymorphism of apolipoprotein(a). J Clin Invest. 1993;91:397–401.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Kronenberg F, König P, Neyer U, et al. Multicenter study of lipoprotein(a) and apolipoprotein(a) phenotypes in patients with end-stage renal disease treated by hemodialysis or continuous ambulatory peritoneal dialysis. J Am Soc Nephrol. 1995;6:110–20.

    CAS  PubMed  Google Scholar 

  19. Stenvinkel P, Heimbürger O, Tuck CH, Berglund L. Apo(a)-isoform size, nutritional status and inflammatory markers in chronic renal failure. Kidney Int. 1998;53:1336–42.

    Article  CAS  PubMed  Google Scholar 

  20. Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int. 1999;55:648–58.

    Article  CAS  PubMed  Google Scholar 

  21. Wanner C, Rader D, Bartens W, et al. Elevated plasma lipoprotein(a) in patients with the nephrotic syndrome. Ann Intern Med. 1993;119:263–9.

    Article  CAS  PubMed  Google Scholar 

  22. Kronenberg F, Lingenhel A, Lhotta K, et al. The apolipoprotein(a) size polymorphism is associated with nephrotic syndrome. Kidney Int. 2004;65:606–12.

    Article  CAS  PubMed  Google Scholar 

  23. Frischmann ME, Kronenberg F, Trenkwalder E, et al. In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients. Kidney Int. 2007;71:1036–43.

    Article  CAS  PubMed  Google Scholar 

  24. De Sain-van der Velden MGM, Reijngoud DJ, Kaysen GA, et al. Evidence for increased synthesis of lipoprotein(a) in the nephrotic syndrome. J Am Soc Nephrol. 1998;9:1474–81.

    Google Scholar 

  25. Kronenberg F, König P, Lhotta K, et al. Apolipoprotein(a) phenotype-associated decrease in lipoprotein(a) plasma concentrations after renal transplantation. Arterioscler Thromb. 1994;14:1399–404.

    Article  CAS  PubMed  Google Scholar 

  26. Kronenberg F, Lhotta K, König P, Margreiter R, Dieplinger H, Utermann G. Apolipoprotein(a) isoform-specific changes of lipoprotein(a) after kidney transplantation. Eur J Hum Genet. 2003;11:693–9.

    Article  CAS  PubMed  Google Scholar 

  27. Kerschdorfer L, König P, Neyer U, et al. Lipoprotein(a) plasma concentrations after renal transplantation: a prospective evaluation after 4 years of follow-up. Atherosclerosis. 1999;144:381–91.

    Article  CAS  PubMed  Google Scholar 

  28. Mora S, Kamstrup PR, Rifai N, Nordestgaard BG, Buring JE, Ridker PM. Lipoprotein(a) and risk of type 2 diabetes. Clin Chem. 2010;56:1252–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Lamina C, Kronenberg F. The mysterious lipoprotein(a) is still good for a surprise. Lancet Diabetes Endocrinol. 2013. doi:10.1016/S2213-8587(13)70085-8.

  30. Kamstrup PR, Nordestgaard BG. Lipoprotein(a) levels, isoform size, and risk of type 2 diabetes: a Mendelian randomisation study. Lancet Diabetes Endocrinol. 2013. doi:10.1016/S2213-8587(13)70064-0.

  31. Cressman MD, Heyka RJ, Paganini EP, O’Neil J, Skibinski CI, Hoff HF. Lipoprotein(a) is an independent risk factor for cardiovascular disease in hemodialysis patients. Circulation. 1992;86:475–82.

    Article  CAS  PubMed  Google Scholar 

  32. Kronenberg F, Neyer U, Lhotta K, et al. The low molecular weight apo(a) phenotype is an independent predictor for coronary artery disease in hemodialysis patients: a prospective follow-up. J Am Soc Nephrol. 1999;10:1027–36.

    CAS  PubMed  Google Scholar 

  33. Kwan BCH, Kronenberg F, Beddhu S, Cheung AK. Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol. 2007;18:1246–61.

    Article  CAS  PubMed  Google Scholar 

  34. Longenecker JC, Klag MJ, Marcovina SM, et al. Small apolipoprotein(a) size predicts mortality in end-stage renal disease: the Choice Study. Circulation. 2002;106:2812–8.

    Article  CAS  PubMed  Google Scholar 

  35. Longenecker JC, Klag MJ, Marcovina SM, et al. High lipoprotein(a) levels and small apolipoprotein(a) size prospectively predict cardiovascular events in dialysis patients. J Am Soc Nephrol. 2005;16:1794–802.

    Article  CAS  PubMed  Google Scholar 

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The author has declared no competing interest.

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Authors and Affiliations

  1. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, 6020, Innsbruck, Austria

    Florian Kronenberg

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  1. Florian Kronenberg
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Correspondence to Florian Kronenberg.

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Kronenberg, F. Causes and consequences of lipoprotein(a) abnormalities in kidney disease. Clin Exp Nephrol 18, 234–237 (2014). https://doi.org/10.1007/s10157-013-0875-8

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  • DOI: https://doi.org/10.1007/s10157-013-0875-8

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