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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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1437-4331
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Volume 43, Issue 5

Issues

Two immunochemical assays to measure advanced glycation end-products in serum from dialysis patients

Xiaohong Zhang / Matthias Frischmann / Rose Kientsch-Engel / Katharina Steinmann / Helga Stopper / Toshimitsu Niwa / Monika Pischetsrieder
Published Online: 2011-09-21 | DOI: https://doi.org/10.1515/CCLM.2005.089

Abstract

Advanced glycation end-products are uremic toxins that accumulate in the serum and tissues of patients with chronic renal failure. Here, we established two enzyme-linked immunosorbent assays (ELISAs) for N ε-carboxymethyllysine and imidazolone to analyze advanced glycation end-products in human serum. Both ELISAs detected advanced glycation end-products bound to human serum albumin in a dose-dependent way. Whereas the formation of imida-zolone was independent of the presence of oxygen, concentrations of N ε-carboxymethyllysine epitopes increased 20-fold under oxidative conditions. The N ε-carboxymethyllysine ELISA showed a similar response to free, peptide-bound and protein-bound N ε-carboxymethyllysine, whereas the imidazolone antibody showed slightly higher affinity toward peptide-bound compared to protein-bound imidazolone. In human serum, linear dilution ranges from 1:10 to 1:40 (N ε-carboxymethyllysine ELISA) and from 1:2 to 1:8 (imidazolone ELISA) were found. The recovery of N ε-carboxymethyllysine from serum was 101±10% and 94±12%, respectively, and 93±15% and 97±12% for imidazolone. The coefficients of variation for intra-assay variability were 0.26–2.7% (N ε-carboxymethyllysine) and 0.1–2.4% (imidazolone), and 8.3–13.4% (N ε-carboxymethyllysine) and 7.8–12.5% (imidazolone) for inter-assay variability. In serum samples from hemodialysis patients (n=20) and controls (n=20), an approximately two-fold increase was detected in the patient group (p<0.001). The combination of the N ε-carboxymethyllysine and imidazolone ELISAs is a valuable tool to measure serum concentrations of advanced glycation end-products for clinical studies.

Keywords: advanced glycation end-products; N ε-carboxymethyllysine (CML); enzyme-linked immunosorbent assay (ELISA); imidazolone; serum

References

  • 1

    Papanastasiou P, Grass L, Rodela H, Patrikarea A, Oreopoulos D, Diamandis E. Immunological quantification of advanced glycosylation end-products in the serum of patients on hemodialysis or CAPD. Kidney Int 1994; 46: 216–22. CrossrefGoogle Scholar

  • 2

    Ateshkadi A, Johnson C, Founds H, Zimmerman S. Serum advanced glycosylation end-products in patients on hemodialysis and CAPD. Perit Dial Int 1995; 15: 129–33. Google Scholar

  • 3

    Takayama F, Aoyama I, Tsukushi S, Miyazaki T, Miyazaki S, Morita T, et al. Immunohistochemical detection of imidazolone and N ε-(carboxymethyl)lysine in aortas of hemodialysis patients. Cell Mol Biol 1997; 44: 1101–9. Google Scholar

  • 4

    Dawnay A, Millar D. The pathogenesis and consequences of AGE formation in uraemia and its treatment. Cell Mol Biol 1997; 44: 1081–94. Google Scholar

  • 5

    Friedlander M, Wu Y, Elgawish A, Monnier V. Early and advanced glycosylation end products. Kinetics of formation and clearance in peritoneal dialysis. J Clin Invest 1996; 97: 728–35. CrossrefGoogle Scholar

  • 6

    Miyata T, Ueda Y, Saito A, Kurokawa K. Carbonyl stress and dialysis-related amyloidosis. Nephrol Dial Transplant 2000; 15(Suppl 1): 25–8. Google Scholar

  • 7

    Miyata T, Fu M, Kurokawa K, van Ypersele de Strihou C, Thorpe S, Baynes J. Autoxidation product of both carbohydrates and lipids are increased in uremic plasma: is there oxidative stress in uremia? Kidney Int 1998; 54: 1290–5. CrossrefGoogle Scholar

  • 8

    Makita Z, Bucala R, Rayfield E, Friedman E, Kaufman A, Korbet S, et al. Reactive glycosylation endproducts in diabetic uremia and treatment of renal failure. Lancet 1994; 343: 1519–22. CrossrefGoogle Scholar

  • 9

    Yanagisawa K, Makita Z, Shiroshita K, Ueda T, Fusegawa T, Kuwajima S, et al. Specific fluorescence assay for advanced glycation end products in blood and urine of diabetic patients. Metabolism 1998; 47: 1348–53. CrossrefGoogle Scholar

  • 10

    Makita Z, Radoff S, Rayfield E, Yang Z, Skolnik E, Delaney V, et al. Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med 1991; 325: 836–42. CrossrefGoogle Scholar

  • 11

    Tsukushi S, Katsuzako T, Aoyama I, Takayama F, Mityazaki T, Shimokata K, et al. Increased erythrocyte 3-DG and AGEs in diabetic hemodialysis patients: role of the polyol pathway. Kidney Int 1999; 55: 1970–6. CrossrefGoogle Scholar

  • 12

    Miyata T, Ueda Y, Yamada Y, Izuhara Y, Wada T, Jadoul M, et al. Accumulation of carbonyls accelerates the formation of pentosidine, an advanced glycation end product: carbonyl stress in uremia. J Am Soc Nephrol 1998; 9: 2349–56. Google Scholar

  • 13

    Miyata T, Wada Y, Cai Z, Iida Y, Horie K, Yasuda Y, et al. Implications of an increased oxidative stress in the formation of advanced glycation endproducts in patients with end-stage renal failure. Kidney Int 1997; 51: 1170–81. CrossrefGoogle Scholar

  • 14

    Münch G, Keis R, Wessels A, Riederer P, Bahner U, Heidland A, et al. Determination of advanced glycation end products in serum by fluorescence spectroscopy and competitive ELISA. Eur J Clin Chem Clin Biochem 1997; 35: 669–77. Google Scholar

  • 15

    Dolhofer-Bliesener R, Lechner B, Deppisch R, Ritz E, Gerbitz K. Immunological determination of advanced glycosylation end-products in human blood and urine. Nephrol Dial Transplant 1995; 10: 657–64. Google Scholar

  • 16

    Odetti P, Cosso L, Pronzato M, Dapino D, Gurreri G. Plasma advanced glycosylation end-products in maintenance haemodialysis patients. Nephrol Dial Transplant 1995; 10: 2110–3. Google Scholar

  • 17

    Friedlander M, Wu Y, Schulak J, Monnier V, Hricik D. Influence of dialysis modality on plasma and tissue concentrations of pentosidine in patients with end-stage renal disease. Am J Kidney Dis 1995; 25: 445–51. CrossrefGoogle Scholar

  • 18

    Kaysen G. The microinflammatory state in uremia: causes and potential consequences. J Am Soc Nephrol 2001; 12: 1549–57. Google Scholar

  • 19

    Aso Y, Inukai K, Takemura Y. Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes. Acta Diabetol 2000; 37: 87–92. CrossrefGoogle Scholar

  • 20

    Pischetsrieder M. Chemistry of glucose and biochemical pathways of biological interest. Perit Dial Int 2000; 20: 26–30. Google Scholar

  • 21

    Degenhardt T, Grass L, Reddy S, Thorpe S, Diamandis E, Baynes J. The serum concentration of the advanced glycation end-product N ε-(carboxymethyl)lysine is increased in uremia. Kidney Int 1997; 52: 1064–7. CrossrefGoogle Scholar

  • 22

    Sell D, Monnier V. End-stage renal disease and diabetes catalyze the formation of a pentose-derived cross-link from aging human collagen. J Clin Invest 1990; 85: 380–4. CrossrefGoogle Scholar

  • 23

    Stein G, Franke S, Mahiout A, Schneider S, Sperschneider H, Borst S, et al. Influence of dialysis modalities on serum AGE levels in end-stage renal disease patients. Nephrol Dial Transplant 2001; 16: 999–1008. Google Scholar

  • 24

    Satoh M, Yamasaki Y, Nagake Y, Kasahara J, Hashimoto M, Nakanishi N, et al. Oxidative stress is reduced by the long-term use of vitamin E-coated dialysis filters. Kidney Int 2001; 59: 1943–50. CrossrefGoogle Scholar

  • 25

    Niwa T, Katsuzaki T, Miyazaki S, Miyazaki T, Ishizaki Y, Hayase F, et al. Immunohistochemical detection of imidazolone, a novel advanced glycation end product, in kidneys and aortas of diabetic patients. J Clin Invest 1997; 99: 1272–80. CrossrefGoogle Scholar

  • 26

    Mellinghoff A, Reininger A, Wuerth J, Founds H, Landgraf R, Hepp K. Formation of plasma advanced glycosylation end products (AGEs) has no influence on plasma viscosity. Diabet Med 1997; 14: 832–6. CrossrefGoogle Scholar

  • 27

    Galler A, Muller G, Schinzel R, Kratzsch J, Kiess W, Munch G. Impact of metabolic control and serum liquids on the concentration of advanced glycation end products in the serum of children and adolescents with type 1 diabetes, as determined by fluorescence spectroscopy and n epsilon-(carboxymethyl)lysine ELISA. Diabetes Care 2003; 26: 2609–15. Google Scholar

  • 28

    Sebekova K, Krajcovicova-Kudlackova M, Schinzel R, Faist V, Klvanova J, Heidland A. Plasma levels of advanced glycation end products in healthy, long-term vegetarians and subjects on a western mixed diet. Eur J Nutr 2001; 40: 275–81. CrossrefGoogle Scholar

  • 29

    Sebekova K, Kupcova V, Schinzel R, Heidland A. Markedly elevated levels of plasma advanced glycation end products in patients with liver cirrhosis – amelioration by liver transplantation. J Hepatol 2002; 36: 66–71. CrossrefGoogle Scholar

  • 30

    Gerdemann A, Lemke HD, Nothdurft A, Heidland A, Munch G, Bahner U, Schinzel R. Low-molecular but not high-molecular advanced glycation end products (AGEs) are removed by high-flux dialysis. Clin Nephrol 2000; 54: 276–83. Google Scholar

  • 31

    Niwa T, Katsuzaki T, Miyazaki S, Momoi T, Akiba T, Miyazaki T, et al. Amyloid beta 2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis. Kidney Int 1997; 51: 187–94. CrossrefGoogle Scholar

  • 32

    Huber B, Pischetsrieder M. Characterization of ascorbylated proteins by immunochemical methods. J Agric Food Chem 1998; 46: 3985–90. CrossrefGoogle Scholar

  • 33

    Fields R. The rapid determination of amino groups with TNBS. Methods Enzymol 1972; 15: 464–8. CrossrefGoogle Scholar

  • 34

    Madson M, Feather M. An improved preparation of 3-deoxy-D-erythro-hexos-2-ulose via the bis(benozoyl-hydrazone) and some related constitutional studies. Carbohydr Res 1981; 94: 183–91. CrossrefGoogle Scholar

  • 35

    Humeny A, Kislinger T, Becker CM, Pischetsrieder M. Qualitative determination of specific protein glycation products by matrix-assisted laser desorption/ionization mass spectrometry peptide mapping. J Agric Food Chem 2002; 50: 2153–60. CrossrefGoogle Scholar

  • 36

    Reddy S, Bichler J, Wells-Knecht K, Thorpe S, Baynes J. N ε-(Carboxymethyl)lysine is a dominant advanced glycation end product (AGE) antigen in tissue proteins. Biochemistry 1995; 34: 10872–8. CrossrefGoogle Scholar

  • 37

    Pischetsrieder M, Larisch B, Seidel W. Immunochemical detection of oxalic acid monoamides which are formed during the oxidative reaction of L-ascorbic acid and proteins. J Agric Food Chem 1997; 45: 2070–5. CrossrefGoogle Scholar

  • 38

    Kalusouva M, Sulkova S, Fialova L, Soukupova J, Malbohan I, Spacek P, et al. Glycoxidation and inflammation in chronic haemodialysis patients. Nephrol Dial Transplant 2003; 18: 2577–81. Google Scholar

  • 39

    Izuhara Y, Miyata T, Ueda Y, Suzuki D, Asahi K, Inagi R, et al. A sensitive and specific ELISA for plasma pentosidine. Nephrol Dial Transplant 1999; 14: 576–80. Google Scholar

  • 40

    Henle T, Deppisch R, Beck W, Hergesell O, Hansch G, Ritz E. Advanced glycation end-products (AGE) during haemodialysis treatment: discrepant results with different methodologies reflecting the heterogeneity of AGE compounds. Nephrol Dial Transplant 1999; 14: 1968–75. Google Scholar

  • 41

    Williams J, Topley N, Craig K, Mackenzie R, Pischetsrieder M, Lage C, et al. The Euro-Balance Trial: the effect of a new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane. Kidney Int 2004; 66: 408–18. CrossrefGoogle Scholar

  • 42

    Schmidt A, Hori O, Chen J, Li J, Crandall J, Zhang J, et al. Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. J Clin Invest 1995; 96: 1395–403. CrossrefGoogle Scholar

  • 43

    Kislinger T, Fu C, Huber B, Qu W, Taguchi A, Yan S, et al. N ε-(Carboxymethyl)lysine adducts of proteins are ligands for RAGE (receptor for AGE) that activate cell signalling pathways and modulate gene expression. J Biol Chem 1999; 274: 31740–9. CrossrefGoogle Scholar

  • 44

    Kislinger T, Tanji N, Qu W, Lu Y, Ferran L, Taguchi A, et al. Receptor for advanced glycation end products mediates inflammation and enhanced expression of tissue factor in vasculature of diabetic apolipoprotein E null mice. Arterioscler Thromb Vasc Biol 2001; 21: 905–10. CrossrefGoogle Scholar

  • 45

    Park L, Raman K, Lee K, Lu Y, Ferran L, Chow W, et al. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med 1998; 4: 1025–31. CrossrefGoogle Scholar

  • 46

    Zimmeck T, Tauer A, Fuenfrocken M, Pischetsrieder M. How to reduce 3-deoxyglucosone and acetaldehyde in peritoneal dialysis fluids. Perit Dial Int 2002; 22: 350–6. Google Scholar

  • 47

    Tauer A, Knerr T, Niwa T, Schaub T, Lage C, Passlick-Deetjen J, et al. In vitro formation of N ε-(carboxymethyl)lysine and imidazolones under conditions similar to continuous ambulatory peritoneal dialysis. Biochem Biophys Res Commun 2001; 280: 1408–14. CrossrefGoogle Scholar

  • 48

    Linden T, Musi B, Järkelid L, Forsbäck G, Kjellstrand P, Deppisch R, et al. Glucose degradation products in peritoneal dialysis fluids may have both local and systemic effects: a study of residual fluid and mesothelial cells. Perit Dial Int 2001; 21: 607–24. Google Scholar

  • 49

    Zhang X, Niwa T, Bosselmann P, Domröse U, Kuhlmann U, Mettang T, et al. Serum imidazolone in CAPD patients treated three months with standard PD fluid (PDF) and three months with the new dual-chambered PDF Balance. Perit Dial Int 2002; 22(Suppl 1): 18. Google Scholar

About the article

Corresponding author: Dr. Monika Pischetsrieder, Institute of Pharmacy and Food Chemistry, University of Erlangen-Nürnberg, Schuhstr. 19, 91052 Erlangen, Germany Phone: +49-9131-852-4102, Fax: +49-9131-852-2587, E-mail:


Received: 2004-11-23

Accepted: 2005-03-03

Published Online: 2011-09-21

Published in Print: 2005-05-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 43, Issue 5, Pages 503–511, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2005.089.

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