Abstract
The atherogenic lipoprotein(a) (Lp(a)) is significantly increased in patients with kidney disease. Some studies in hemodialysis patients described this increase to be dependent on the genetic apolipoprotein(a) (apo(a)) isoforms. Only patients who express high molecular weight (HMW) apo(a) isoforms but not those with low molecular weight (LMW) isoforms show a relative increase of Lp(a) when compared to healthy controls matched for apo(a) isoforms. However, this was not confirmed by all studies. We therefore prospectively investigated the changes of Lp(a) deriving from each apo(a) isoform in heterozygotes following kidney transplantation. Lp(a) concentrations were measured by ELISA. To calculate the isoform-specific concentrations and the changes of Lp(a) deriving from each isoform, we densitometrically scanned the apo(a) bands from immunoblots before and after transplantation in 20 patients expressing two apo(a) isoforms. Of these, 10 patients expressed both an LMW and an HMW apo(a) isoform. The other 10 patients expressed only HMW isoforms. Densitometric scanning of apo(a) bands and calculation of isoform-derived Lp(a) concentrations clearly demonstrated that the decrease of Lp(a) following kidney transplantation is caused by changes in the expression of HMW apo(a) isoforms. In some patients, we observed an almost complete disappearance of the HMW apo(a) isoform after transplantation. This study clearly demonstrates that the changes of Lp(a) plasma concentrations in kidney disease depend on the genetically determined size of apo(a). This provides evidence for an interaction of apo(a) genetic variability and kidney function on Lp(a) concentrations.
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References
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: 458–465.
Lackner C, Boerwinkle E, Leffert CC, Rahmig T, Hobbs HH : Molecular basis of apolipoprotein (a) isoform size heterogeneity as revealed by pulsed-field gel electrophoresis. J Clin Invest 1991; 87: 2153–2161.
Boerwinkle E, Leffert CC, Lin J, Lackner C, Chiesa G, Hobbs HH : Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest 1992; 90: 52–60.
Kraft HG, Köchl S, Menzel HJ, Sandholzer C, Utermann G : The apolipoprotein(a) gene: a transcribed hypervariable locus controlling plasma lipoprotein(a) concentration. Hum Genet 1992; 90: 220–230.
Kronenberg F, Steinmetz A, Kostner GM, Dieplinger H : Lipoprotein(a) in health and disease. Crit Rev Clin Lab Sci 1996; 33: 495–543.
Kronenberg F, Utermann G, Dieplinger H : Lipoprotein(a) in renal disease. Am J Kidney Dis 1996; 27: 1–25.
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.
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: 110–120.
Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C : Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999; 55: 648–658.
Milionis HJ, Elisaf MS, Tselepis A, Bairaktari E, Karabina SA, Siamopoulos KC : Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with renal failure. Am J Kidney Dis 1999; 33: 1100–1106.
Hirata K, Kikuchi S, Saku K et al: Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance hemodialysis patients with/without diabetes mellitus. Kidney Int 1993; 44: 1062–1070.
Auguet T, Sentí M, Rubies-Prat J et al: Serum lipoprotein(a) concentration in patients with chronic renal failure receiving haemodialysis: influence of apolipoprotein(a) genetic polymorphism. Nephrol Dial Transplant 1993; 8: 1099–1103.
Gazzaruso C, Bonetti G, Garzaniti A et al: Increased plasma concentrations of lipoprotein(a) for every phenotype of apolipoprotein(a) in patients with chronic renal failure treated by hemodialysis. Nutr Metab Cardiovasc Dis 1996; 6: 203–210.
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: 1399–1404.
Kronenberg F, Lobentanz E-M, König P, Utermann G, Dieplinger H : Effect of sample storage on the measurement of lipoprotein(a), apolipoproteins B and A-IV, total and high-density lipoprotein cholesterol and triglycerides. J Lipid Res 1994; 35: 1318–1328.
Kronenberg F, Trenkwalder E, Kronenberg MF, König P, Utermann G, Dieplinger H : Influence of hematocrit on the measurement of lipoproteins demonstrated by the example of lipoprotein(a). Kidney Int 1998; 54: 1385–1389.
Kamboh MI, Ferrell RE, Kottke BA : Expressed hypervariable polymorphism of apolipoprotein (a). Am J Hum Genet 1991; 49: 1063–1074.
Kraft HG, Lingenhel A, Bader G, Kostner GM, Utermann G : The relative electrophoretic mobility of apo(a) isoforms depends on the gel system: proposal of a nomenclature for apo(a) phenotypes. Atherosclerosis 1996; 125: 53–61.
Dieplinger H, Gruber G, Krasznai K et al: Kringle 4 of human apolipoprotein[a] shares a linear antigenic site with human catalase. J Lipid Res 1995; 36: 813–822.
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: 105–115.
Koch M, Kutkuhn B, Trenkwalder E et al: Apolipoprotein B, fibrinogen, HDL cholesterol and apolipoprotein(a) phenotypes predict coronary artery disease in hemodialysis patients. J Am Soc Nephrol 1997; 8: 1889–1898.
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: 1755–1763.
Oida K, Takai H, Maeda H et al: Apolipoprotein(a) is present in urine and its excretion is decreased in patients with renal failure. Clin Chem 1992; 38: 2244–2248.
Mooser V, Seabra MC, Abedin M, Landschulz KT, Marcovina S, Hobbs HH : Apolipoprotein(a) kringle 4-containing fragments in urine. Relationship to plasma levels of lipoprotein(a). J Clin Invest 1996; 97: 858–864.
Kostner KM, Maurer G, Huber K et al: Urinary excretion of apo(a) fragments. Role in apo(a) catabolism. Arterioscler Thromb Vase Biol 1996; 16: 905–911.
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: 2414–2424.
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: 381–391.
Acknowledgements
This study was supported by grants from the Austrian National Bank (Project 9331), the ‘Österreichischer Herzfonds’, the ‘Else Kröner-Fresenius Stiftung’ and the Knoll William Harvey Prize to Florian Kronenberg and by Grants P-12358 and P-15480 from the Austrian Science Fund to Hans Dieplinger and Gerd Utermann, respectively.
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Kronenberg, F., Lhotta, K., König, P. et al. Apolipoprotein(a) isoform-specific changes of lipoprotein(a) after kidney transplantation. Eur J Hum Genet 11, 693–699 (2003). https://doi.org/10.1038/sj.ejhg.5201016
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DOI: https://doi.org/10.1038/sj.ejhg.5201016
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