Skip to main content

Advertisement

Log in

Oxidative stress in children on hemodialysis: value of autoantibodies against oxidized low-density lipoprotein

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

The principal causes of morbidity and mortality in children with chronic renal failure on maintenance hemodialysis are cardiovascular complications. Recently, it has been suggested that oxidative stress, chronic inflammation and malnutrition are risk factors for cardiovascular disease. However, to date, biomarkers of oxidative stress have not been well studied in children. The aim of this study was to investigate the relationship between oxidative stress and cardiovascular risk factors in children on hemodialysis therapy. Twenty-eight hemodialysis patients (13 females, 15 males; mean age 15.1 ± 2.5 years) and 20 healthy children (13 females, seven males; mean age 14.3 ± 2.7 years) were included in the study. Levels of antibodies to oxidized low-density lipoprotein (oLABs), high sensitivity C-reactive protein (hs-CRP), albumin, prealbumin, transferrin, and ferritin were measured. Antibodies to oxidized low-density lipoprotein (LDL) in hemodialysis patients were lower than those in the controls (P < 0.05). The patients with lower oLAB titers had higher levels of hs-CRP and ratio of erythropoietin to hematocrit (EPO/Htc), and lower levels of albumin, prealbumin, apolipoprotein A-1 (ApoA1), and high-density lipoprotein (P < 0.05). Antibodies to oxidized LDL in hemodialysis patients with dyslipidemia were lower than those of patients with normal lipid profile (P < 0,05). This study showed that children treated by hemodialysis are exposed to oxidative stress and chronic inflammation. We suggest that oLAB levels are decreased in children on hemodialysis as a result of severe oxidative stress and that these antibodies are related to inflammation, anemia, malnutrition and dyslipidemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Gruppen MP, Groothoff JW, Prins M (2003) Cardiac disease in young adult patients with end-stage renal disease since childhood: a Dutch cohort study. Kidney Int 63:1058–1065

    Article  PubMed  Google Scholar 

  2. Parekh RS, Carroll CE, Wolfe RA (2000) Cardiovascular mortality in children and young adults with end-stage kidney disease. J Pediatr 141:191–197

    Article  Google Scholar 

  3. Mitsnefes MM (2002) Pediatric end-stage renal disease: heart as a target. J Pediatr 141:162–164

    Article  PubMed  Google Scholar 

  4. Scharer K, Schmidt KG, Soergel M (1999) Cardiac function and structure in patients with chronic renal failure. Pediatr Nephrol 13:951–965

    Article  CAS  PubMed  Google Scholar 

  5. Mitsnefes MM (2008) Cardiovascular complications of pediatric chronic kidney disease. Pediatr Nephrol 23:27–39

    Article  PubMed  PubMed Central  Google Scholar 

  6. Stenvinkel P, Heimburger O, Paulture F (1999) Strong association between malnutrition, inflammation and atherosclerosis in chronic renal failure. Kidney Int 55:1899–1911

    Article  CAS  PubMed  Google Scholar 

  7. Stenvinkel P (2003) Interactions between inflammation, oxidative stress and endothelial dysfunction in end-stage renal disease. J Ren Nutr 13:144–148

    Article  PubMed  Google Scholar 

  8. Oberg BP, McMenamin E, Lucas FL (2004) Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int 65:1009–1016

    Article  PubMed  Google Scholar 

  9. Spittle MA, Hoenich NA, Handelman GJ (2001) Oxidative stress and inflammation in hemodialysis patients. Am J Kidney Dis 38:1408–1413

    Article  CAS  PubMed  Google Scholar 

  10. Dasgupta A, Hussain S, Ahmad S (1992) Increased lipid peroxidation in patients on maintenance hemodialysis. Nephron 60:56–59

    Article  CAS  PubMed  Google Scholar 

  11. Toborek M, Wasık T, Drozdz M (1992) Effect of hemodialysis on lipid peroxidation and antioxidant system in patients with chronic renal failure. Metabolism 41:1229–1232

    Article  CAS  PubMed  Google Scholar 

  12. Nguyen-Khoa T, Massy ZA, De Bandt JP (2001) Oxidative stress and hemodialysis: role of inflammation and duration of dialysis treatment. Nephrol Dial Transplant 16:335–340

    Article  CAS  PubMed  Google Scholar 

  13. Panichi V, Migliori M, De Pietro S (2000) The link of biocompatibility to cytokine production. Kidney Int 58:96–103

    Article  Google Scholar 

  14. Kaysen GA, Eiserich JP (2003) Characteristics and effects of inflammation in end-stage renal disease. Semin Dial 16:438–446

    Article  PubMed  Google Scholar 

  15. Maroti Z, Nemeth I, Turi S (2004) Heme oxygenase 1 expression in young uremic patients on hemodialysis. Pediatr Nephrol 19:426–431

    Article  PubMed  Google Scholar 

  16. Ece A, Gurkan F, Kervancioglu M, Kocamaz H, Gunes A, Atamer Y, Selek S (2006) Oxidative stress, inflammation and early cardiovascular damage in children with chronic renal failure. Pediatr Nephrol 21:545–552

    Article  PubMed  Google Scholar 

  17. Berliner JA, Navab M, Fogelman AM (1995) Atherosclerosis: basic mechanisms and oxidation, inflammation and genetics. Circulation 91:2488–2496

    Article  CAS  PubMed  Google Scholar 

  18. Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809

    Article  CAS  PubMed  Google Scholar 

  19. Steinbrecher UP, Zhang HF, Lougheed M (1990) Role of oxidatively modified LDL in atherosclerosis. Free Radic Biol Med 9:155–168

    Article  CAS  PubMed  Google Scholar 

  20. Steinberg D, Parathasarathy S, Carew TE (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320:915–924

    Article  CAS  PubMed  Google Scholar 

  21. Witztum JL (1993) Role of oxidized low-density lipoprotein in atherogenesis. Br Heart J 69:12–13

    Article  Google Scholar 

  22. Brown MS, Goldstein J (1983) Lipoprotein metabolism in the macrophage. Ann Rev Biochem 52:223–261

    Article  CAS  PubMed  Google Scholar 

  23. Yl-Herttuala S, Palinski W, Rosenfeld ME, Parthasarathy S, Carew TE, Butler S, Witztum JL, Steinberg D (1989) Evidence for the presence of oxidatively modified LDL in atherosclerotic lesions of rabbit and man. J Clin Invest 284:1086–1095

    Article  Google Scholar 

  24. Maggi E, Bellazzi R, Falaschi F (1994) Enhanced LDL oxidation in uremic patients: an additional mechanism for accelerated atherosclerosis? Kidney Int 45:876–883

    Article  CAS  PubMed  Google Scholar 

  25. Loughrey CM, Young IS, Lighbody JH (1994) Oxidative stress in hemodialysis. Q J Med 87:679–683

    CAS  Google Scholar 

  26. Nemeth I, Turi S, Haszon I (2000) Vitamin E alleviates the oxidative stress of erythropoietin in uremic children on hemodialysis. Pediatr Nephrol 14:13–17

    Article  CAS  PubMed  Google Scholar 

  27. Shoji T, Nishizawa Y, Fukumoto M (2000) Inverse relationship between circulating oxidized low density lipoprotein and anti-oxLDL antibody levels in healthy subjects. Atherosclerosis 148:171–177

    Article  CAS  PubMed  Google Scholar 

  28. Fukumoto M, Shoji T, Emoto M (2000) Antibodies against oxidized LDL and carotid intima media thickness in a healthy population. Atheroscler Thromb Vasc Biol 20:703–707

    Article  CAS  Google Scholar 

  29. American Academy of Pediatrics, National Cholesterol Education Program (1992) Report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 89:525–564

    Article  Google Scholar 

  30. Tinahones FJ, Gomez-Zumaquero JM, Garrido-Sanchez L, Garcia-Fuentes E, Rojo-Martinez G, Esteva I, Adana MS, Cardona F, Soriguer F (2005) Influence of age and sex on levels of anti-oxidized LDL antibodies and anti-LDL immune complexes in the general population. J Lipid Res 46:452–457

    Article  CAS  PubMed  Google Scholar 

  31. Salonen JT, Yla Herttula S, Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssönen K, Palinski W, Witztum JL (1992) Autoantibodies against oxidized LDL and progression of carotid atherosclerosis. Lancet 339:883–887

    Article  CAS  PubMed  Google Scholar 

  32. Maggi E, Bellazzi R, Gazo A (1994) Autoantibodies against oxidatively modified LDL in uremic patients undergoing dialysis. Kidney Int 46:869–876

    Article  CAS  PubMed  Google Scholar 

  33. Bergesio F, Monzani G, Ciuti R (2001) Autoantibodies against oxidized LDL in chronic renal failure: role of renal function, diet and lipids. Nephron 87:127–133

    Article  CAS  PubMed  Google Scholar 

  34. Palinsky W, Miller E, Witztum JL (1995) Immunization of low-density lipoprotein receptor deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis. Proc Natl Acad Sci U S A 92:821–825

    Article  Google Scholar 

  35. Rosealar SE, Schonfeld G, Daugherty A (1995) Enhanced development of atherosclerosis in cholesterol-fed rabbits by suppression of cell-mediated immunity. J Clin Invest 96:1389–1394

    Article  Google Scholar 

  36. Horkko S, Binder JC, Shaw PX (2000) Immunological responses to oxidized LDL. Free Radic Biol Med 28:1771–1779

    Article  CAS  PubMed  Google Scholar 

  37. Khoschsorur G, Tatzber F, Freigassner M (1996) Inverse correlation of MDA and anti-oxLDL IgG antibodies in transplantation patients. Med Sci Res 24:851–856

    CAS  Google Scholar 

  38. Shoji T, Fukumoto M, Emoto M (2002) Antibody to oxidized low-density lipoprotein and cardiovascular mortality in end-stage renal disease. Kidney Int 62:2230–2237

    Article  CAS  PubMed  Google Scholar 

  39. Shoji T, Kimoto E, Shinohara K (2003) The association of antibodies against low-density lipoprotein with atherosclerosis in hemodialysis patients. Kidney Int 84:128–130

    Article  Google Scholar 

  40. Festa A, Kopp H, Schernthaner G (1998) Autoantibodies to oxidized low-density lipoproteins in IDDM are inversely related to metabolic control and microvascular complications. Diabetologia 41:350–356

    Article  CAS  PubMed  Google Scholar 

  41. Panichi V, Migliori M, De Pietro S (2001) C reactive protein in patients with chronic renal failure. Ren Fail 23:551–562

    Article  CAS  PubMed  Google Scholar 

  42. Besbas N, Ozdemir S, Saatci U (1998) Nutritional assessment of children on hemodialysis: value of IGF-I, TNF-alpha and IL-Ibeta. Nephrol Dial Transplant 13:1484–1488

    Article  CAS  PubMed  Google Scholar 

  43. Ekim M, Ikinciogulları A, Ulukol B (2003) Evaluation of nutritional status and factors related to malnutrition in children on CAPD. Perit Dial Int 23:557–562

    Article  CAS  PubMed  Google Scholar 

  44. Kaysen G, Rathore V, Shearer GC (1995) Mechanisms of hypoalbuminemia in hemodialysis patients. Kidney Int 48:510–516

    Article  CAS  PubMed  Google Scholar 

  45. Sezer S, Ozdemir FN, Arat Z (2002) Triad of malnutrition, inflammation, and atherosclerosis in hemodialysis patients. Nephron 91:456–462

    Article  PubMed  Google Scholar 

  46. Kaysen GA, Dublin JA, Müller HG (2000) The acute phase response varies with time and predicts serum albumin levels in hemodialysis patients. Kidney Int 58:346–352

    Article  CAS  PubMed  Google Scholar 

  47. Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd (1998) Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med 338:1650–1656

    Article  CAS  PubMed  Google Scholar 

  48. Goodman WG, Goldin J, Kuizon BD (2000) Coronary artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342:1478–1483

    Article  CAS  PubMed  Google Scholar 

  49. Querfeld U (2002) Is atherosclerosis accelerated in young patients with end-stage renal disease? The contribution of paediatric nephrology. Nephrol Dial Transplant 17:719–722

    Article  PubMed  Google Scholar 

  50. Samuelson O, Attman PO, Knight-Gibson C (1994) Lipoprotein abnormalities without hyperlipidemia in moderate renal insufficiency. Nephrol Dial Transplant 9:1580–1585

    Google Scholar 

  51. Attman PO, Alaupovic P, Tavella M (1996) Abnormal lipid and apolipoprotein composition of major lipoprotein density classes in patients with chronic renal failure. Nephrol Dial Transplant 11:63–69

    Article  CAS  PubMed  Google Scholar 

  52. Zacchello G, Pagnan A, Sidran MP (1987) Further definition of lipid-lipoprotein abnormalities in children with various degrees of chronic renal insufficiency. Pediatr Res 21:462–465

    Article  CAS  PubMed  Google Scholar 

  53. Turi S, Nemeth I, Vargha I (1991) Erythrocyte defense mechanisms against free oxygen radicals in haemodialysed uraemic children. Pediatr Nephrol 5:179–183

    Article  CAS  PubMed  Google Scholar 

  54. Gunnel J, Yeun JY, Depner TA (1999) Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients. Am J Kidney Dis 33:63–72

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nurcan Cengiz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cengiz, N., Baskin, E., Sezgin, N. et al. Oxidative stress in children on hemodialysis: value of autoantibodies against oxidized low-density lipoprotein. Pediatr Nephrol 24, 387–393 (2009). https://doi.org/10.1007/s00467-008-1004-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-008-1004-x

Keywords

Navigation