Journal Mobile Options
Table of Contents
Vol. 36, No. 4, 2012
Issue release date: October 2012
Am J Nephrol 2012;36:317–323
(DOI:10.1159/000342235)

Main Determinants of PON1 Activity in Hemodialysis Patients

Ribeiro S. · do Sameiro Faria M. · Mascarenhas-Melo F. · Freitas I. · Mendonça M.I. · Nascimento H. · Rocha-Pereira P. · Miranda V. · Mendonça D. · Quintanilha A. · Belo L. · Costa E. · Reis F. · Santos-Silva A.
aFaculdade de Farmácia, Serviço de Bioquímica, bInstituto de Biologia Molecular e Celular, Universidade do Porto, Porto, cFMC, Dinefro – Diálises e Nefrologia, SA, Maia, dInstituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, eLaboratório de Farmacologia e Terapêutica Experimental, IBILI, Faculdade de Medicina, Universidade de Coimbra, Coimbra, fUnidade de Investigação, Hospital Central do Funchal, gLaboratório de Genética Humana, Campus Universitário da Penteada, Funchal, hCentro Investigação Ciências Saúde, Universidade Beira Interior, Covilhã, iInstituto de Saúde Pública da Universidade do Porto, and jInstituto de Ciências da Saúde da Universidade Católica Portuguesa, Porto, Portugal

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Background/Aims: Cardiovascular diseases are the major cause of morbidity and mortality in hemodialysis (HD) patients. These patients present reduced paraoxonase 1 (PON1) activity that depends on genetic and non-genetic factors; however, how these factors influence PON1 activity in HD patients is poorly clarified. Our aim was to evaluate the influence of two polymorphisms and non-genetic factors on PON1 activity in HD patients. Methods: We evaluated 183 HD patients under recombinant human erythropoietin (rhEPO) treatment and 22 healthy individuals. The lipid profile [total cholesterol, triglycerides, HDL-c, LDL-c, apolipoprotein (Apo) A-I, Apo B, lipoprotein(a) and oxidized low-density lipoprotein (Ox-LDL)], inflammatory markers [adiponectin, interleukin-6 (IL-6) and C-reactive protein (CRP)], PON1 activity and PON1 gene polymorphisms (L55M and Q192R) were evaluated. Results: HD patients presented higher levels of IL-6, CRP and Ox-LDL/LDL-c, and lower PON1 activity, total cholesterol, HDL-c, LDL-c, Apo A and Apo B; the most frequent genotype was heterozygosity for L55M polymorphism and homozygosity for the Q allele, the more frequent genotype of Q192R polymorphism. Multiple regression analysis identified heterozygosity and homozygosity for L55M and Q192R polymorphisms, very low-density lipoproteins, LDL-c, Apo A and CRP levels, time on dialysis and rhEPO dose, as the independent variables significantly associated with PON1 activity. The associations with CRP, rhEPO and time on dialysis were negative. Conclusion: Our results show that the reduced PON1 activity in HD patients who are not under statin therapy is strongly associated with inflammation, longer time on dialysis and high rhEPO doses, suggesting that the reduction in PON1 activity may worsen the prognosis of these patients.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Kimak E, Halabis M, Baranowicz-Gaszczyk I, Solski J, Ksiazek A: Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients. J Zhejiang Univ Sci B 2011;12:365–371.
  2. Deakin S, Moren X, James RW: Very low density lipoproteins provide a vector for secretion of paraoxonase-1 from cells. Atherosclerosis 2005;179:17–25.
  3. Kundhal K, Lok CE: Clinical epidemiology of cardiovascular disease in chronic kidney disease. Nephron Clin Pract 2005;101:c47–c52.
  4. Biasioli S, Schiavon R, Petrosino L, De Fanti E, Cavalcanti G, Battaglia P, Fasolin A: Paraoxonase activity and paraoxonase 1 gene polymorphism in patients with uremia. ASAIO J 2003;49:295–299.
  5. Rajkovic MG, Barisic K, Juretic D, Grubisic TZ, Flegar-Mestric Z, Rumora L: Polymorphisms of PON1 and PON2 genes in hemodialyzed patients. Clin Biochem 2011;44:964–968.
  6. Rozek LS, Hatsukami TS, Richter RJ, Ranchalis J, Nakayama K, McKinstry LA, Gortner DA, Boyko E, Schellenberg GD, Furlong CE, Jarvik GP: The correlation of paraoxonase (PON1) activity with lipid and lipoprotein levels differs with vascular disease status. J Lipid Res 2005;46:1888–1895.
  7. Rajkovic MG, Rumora L, Juretic D, Grubisic TZ, Flegar-Mestric Z, Vrkic N, Sinjeri Z, Barisic K: Effect of non-genetic factors on paraoxonase 1 activity in patients undergoing hemodialysis. Clin Biochem 2010;43:1375–1380.
  8. Schrader C, Rimbach G: Determinants of paraoxonase 1 status: genes, drugs and nutrition. Curr Med Chem 2011;18:5624–5643.
  9. Locatelli F, Aljama P, Barany P, Canaud B, Carrera F, Eckardt KU, Horl WH, Macdougal IC, Macleod A, Wiecek A, Cameron S: Revised European Best Practice Guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004;19(suppl 2):ii1–ii47.

    External Resources

  10. Olerup O, Zetterquist H: HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours: an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens 1992;39:225–235.
  11. Gaffney D, Campbell RA: A PCR based method to determine the Kalow allele of the cholinesterase gene: the E1k allele frequency and its significance in the normal population. J Med Genet 1994;31:248–250.
  12. Precourt LP, Amre D, Denis MC, Lavoie JC, Delvin E, Seidman E, Levy E: The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis 2011;214:20–36.
  13. Atchley DH, Lopes-Virella MF, Zheng D, Kenny D, Virella G: Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy. Diabetologia 2002;45:1562–1571.
  14. Lopes-Virella MF, Virella G: Clinical significance of the humoral immune response to modified LDL. Clin Immunol 2010;134:55–65.
  15. Rainwater DL, Rutherford S, Dyer TD, Rainwater ED, Cole SA, Vandeberg JL, Almasy L, Blangero J, Maccluer JW, Mahaney MC: Determinants of variation in human serum paraoxonase activity. Heredity (Edinb) 2009;102:147–154.
  16. James RW, Deakin SP: The importance of high-density lipoproteins for paraoxonase-1 secretion, stability, and activity. Free Radic Biol Med 2004;37:1986–1994.
  17. Tian L, Fu M: The relationship between high density lipoprotein subclass profile and apolipoprotein concentrations. J Endocrinol Invest 2011;34:461–472.
  18. Cuevas X, Garcia F, Martin-Malo A, Fort J, Llados F, Lozano J, Perez-Garcia R: Risk factors associated with cardiovascular morbidity and mortality in Spanish incident hemodialysis patients: two-year results from the ANSWER study. Blood Purif 2012;33:21–29.

    External Resources

  19. Henning BF, Holzhausen H, Tepel M: Continuous reduction of plasma paraoxonase activity with increasing dialysis vintage in hemodialysis patients. Ther Apher Dial 2010;14:572–576.
  20. Marsillach J, Martinez-Vea A, Marcas L, Mackness B, Mackness M, Ferre N, Joven J, Camps J: Administration of exogenous erythropoietin beta affects lipid peroxidation and serum paraoxonase-1 activity and concentration in predialysis patients with chronic renal disease and anaemia. Clin Exp Pharmacol Physiol 2007;34:347–349.
  21. Costa E, Lima M, Alves JM, Rocha S, Rocha-Pereira P, Castro E, Miranda V, do SF, Loureiro A, Quintanilha A, Belo L, Santos-Silva A: Inflammation, T-cell phenotype, and inflammatory cytokines in chronic kidney disease patients under hemodialysis and its relationship to resistance to recombinant human erythropoietin therapy. J Clin Immunol 2008;28:268–275.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50