PLASMA CYTOKINES LEVELS IN PATIENTS UNDERGOING LONG-TERM HAEMODIALYSIS

Аbstract.  Patients  with  end-stage  renal  disease  need  their  kidney  functions  to  be  replaced.  Chronic haemodialysis represents a most common method of such substitution treatment. This procedure results in successful survival of such patients for years. Chronic haemodialysis is accompanied by a complication which is known as β2-microglobulin amyloidosis. In this case, amyloid substance consisting of β2-microglobulin (β2-MG) accumulates in bones, ligaments and joints. Biological causes of β2-MG amyloidosis are still not established. To elucidate the role of inflammation in the pathogenesis of β2-MG amyloidosis, the levels of  IL-2,  IL-4,  IL-6,  IL-8,  IL-10,  GM-CSF,  IFNγ, TNFα were quantified in plasma of patients undergoing  long-term haemodialysis. Mean amounts of all the mentioned cytokines in haemodialysis patients proved to be significantly higher than in control group consisting of healthy subjects. When comparing a group receiving standard  dialysis  procedure  versus  a  subgroup  receiving  haemodiafiltration,  a  single  reliable  difference  was revealed for GM-CSF levels (p < 0.04), without any differences shown for other cytokines. With increasing terms of chronic haemodialysis, the levels of IL-2, IL-4, IL-6, IL-8, GM-CSF, IFNγ, TNFα were increased, or, at least, they did not decrease. After three years of dialysis, IL-10 concentrations were statistically indistinguishable from normal levels. In patients undergoing haemodiafiltration, plasma levels of IL-2, IL-4, IL-8, GM-CSF, IFNγ, TNFα did not drop with increasing terms of dialysis. The levels of IL-6 and IL-10 decreased after three years of dialysis, to near-normal levels.In general, these results suggest that IL-10 and IL-6 may be regarded as candidates for further studies as potential markers of β2-microglobulin amyloidosis. (Med. Immunol., 2011, vol. 13, N 2-3, pp 211-218)

1. Поляков Д.С., Грудинина Н.А., Соловьев К.В., Егоров В.В., Сироткин А.К., Алейникова Т.Д., Тотолян Арег А., Шавловский М.М. Бета-2-микроглобулиновый амилоидоз: фибриллогенез природного и рекомбинантных бета-2микроглобулинов человека // Медицинский академический журнал. – 2010. – Т. 10, № 2. – С. 40-49.

2. Поляков Д.С., Тотолян Арег А., Шавловский М.М. Получение природного бета2микроглобулина человека // Молекулярная медицина. – 2010. – № 6. – С. 39-43.

3. Соловьев К.В., Грудинина Н.А., Семернин Е.Н., Морозова В., Смирнова С.А., Поляков Д.С., Алейникова Т.Д., Шляхто Е.В., Гудкова А.Я., Шавловский М.М. Мутации V30M, H90N и del9 в гене транстиретина у больных с кардиомиопатиями в Санкт-Петербурге // Генетика. – 2011. – Т. 47, № 2. – С. 1-7.

4. Шило В. Позднее осложнение программного гемодиализа: бета 2-микроглобулиновый амилоидоз. В. Шило, А. Денисов // Врач: Ежемесячный научно-практический и публицистический журнал. – 2002. – № 6. – С. 7-12.

5. Benz R.L., Siegfried J.W., Teehan B.P. Carpal tunnel syndrome in dialysis patients: Comparison between continuous ambulatory peritoneal dialysis and hemodialysis populations // Am. J. Kidney Dis. – 1988. – N 11. – Р. 473-476.

6. Campistol J.M., Sole M., Munoz-Gomez J., Lopez-Pedret J., Revert L. Systemic involvement of dialysis-amyloidosis // Am. J. Nephrol. – 1990. – N 10. – Р. 389-396.

7. Cavaillon J.M., Poignet J.L., Fitting C., Delons S. Serum interleukin-6 in long-term hemodialyzed patients // Nephron. – 1992. – 60. – Р. 307-313.

8. Cornelis F., Bardin T., Faller B. et al. Rheumatic syndromes and beta 2-microglobulin amyloidosis in patients receiving long-term peritoneal dialysis // Arthritis Rheum. – 1989. – N 32. – Р. 785-788.

9. Descamps-Latscha B., Herbelin A., Nguyen A.T. et al. Balance between IL-1 betaTNF-α, and their specific inhibitors in chronic renal failure and maintenance dialysis. Relationships with activation markers of T cells, B cells, and monocytes // J. Immunol. – 1995. – 154. – Р. 882-892.

10. Gal R., Korzets A., Schwartz A., RathWolfson L., Gafter U. Systemic distribution of beta 2-microglobulin-derived amyloidosis in patients who undergo long-term hemodialysis. Report of seven cases and review of the literature // Arch. Pathol. Lab. Med. – 1994. – N 118. – Р. 718-721.

11. Herbelin A., Urena P., Nguyen A.T., Zingraff J., Descamps-Latscha B. Elevated circulating levels of interleukin-6 in patients with chronic renal failure // Kidney Int. – 1991. – 39. – Р. 954-960.

12. Jadoul M., Garbar C., Noёl H., Sennesael J., Vanholder R., Bernaert P., Rorive G., Hanique G., van Ypersele, de Strihou C. Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a prospective post-mortem study // Kidney Int. – 1997. – Jun; 51 (6). – Р. 1928-1932.

13. Kaizu Y., Kimura M., Yoneyama T. et al. Interleukin-6 may mediate malnutrition in chronic hemodialysis patients // Am. J. Kidney Dis. – 1998. – 31. – Р. 93-100.

14. Ketteler M., Koch K.M., Floege J. Imaging techniques in the diagnosis of dialysis-related amyloidosis // Semin Dial. – 2001. – Mar-Apr; 14 (2). – Р. 90-3. mmunologic function and survival in hemodialysis patients // Kidney Int. – 1998. – 54. – Р. 236-244.

15. Libetta C., De Nicola L., Rampino T., De Simone W., Memoli B. Inflammatory effects of peritoneal dialysis: evidence of systemic monocyte activation //Kidney Int. – 1996. – 49. – Р. 506-511.

16. Loughrey C.M., Young I.S., Lightbody J.H., McMaster D., McNamee P.T., Trimble E.R. Oxidative stress in haemodialysis // QJM87. – 1994. – Р. 679-683.

17. Massry S.G., Coburn J.W. Guideline 10. β2-microglobulin amyloidosis // Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease / American Journal of Kidney Diseases. – 2003. – Vol. 42, Suppl 3. – P. 1-202.

18. Miyata T., van Ypersele de Strihou C., Kurokawa K., Baynes J.W. Alterations in nonenzymatic biochemistry in uremia: origin and significance of ‘‘carbonyl stress’’ in long-term uremic complications // Kidney Int. – 1999. – 55. – Р. 389-399.

19. McGrath LT., Douglas A.F., McClean E., Brown J.H., Doherty C.C., Johnston G.D., Archbold G.P. Oxidative stress and erythrocyte membrane fluidity in patients undergoing regular dialysis // Clin. Chim. Acta. – 1995. – N 235. – Р. 179-188.

20. Moriniere P., Marie A., el Esper N., Fardellone P., Deramond H., Remond A., Sebert J.L., Fournier A. Destructive spondyloarthropathy with beta 2-microglobulin amyloid deposits in a uremic patient before chronic hemodialysis // Nephron. – 1991. – N 59. – Р. 654-657.

21. Naugle K., Darby M.L., Bauman D.B., Lineberger L.T., Powers R. The oral health status of individuals on renal dialysis // Ann Periodontol. – 1998. – N 3. – Р. 197-205.

22. Odetti P., Cosso L., Pronzato M.A., Dapino D., Gurreri G. Plasma advanced glycosylation endproducts in maintenance haemodialysis patients // Nephrol Dial Transplant. – 1995. – Nov. 10 (11). – Р. 2110-2113.

23. Ohashi K., Hara M., Kawai R., Ogura Y., Honda K., Nihei H., Mimura N. Cervical discs are most susceptible to beta 2-microglobulin amyloid deposition in the vertebral column // Kidney Int. – 1992. – N 41. – Р. 1646-1652.

24. Palestro C.J., Vega A., Kim C.K., Vallabhajosula S., Goldsmith S.J. Indium-111-labeled leukocyte scintigraphy in hemodialysis access-site infection // J. NuclMed. – 1990. – N 31. – Р. 319-324.

25. Pereira B.J., Shapiro L., King A.J., Falagas M.E., Strom J.A., Dinarello C.A. Plasma levels of IL-1 beta, TNF-α and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients // Kidney Int. – 1994. – N 45. – Р. 890-896.

26. Pereira B.J., Snodgrass B.R., Hogan P.J., King A.J. Diffusive and convective transfer of cytokine-inducing bacterial products across hemodialysis membranes // Kidney Int. – 1995. – N 47. – Р. 603-610.

27. Sheikh-Hamad D., Ayus J.C. The patient with a clotted PTFE graft developing fever // Nephrol Dial Transplant. – 1998. – N 13. – Р. 2392-2393.

28. Sprague S.M., Moe S.M. Clinical manifestations and pathogenesis of dialysis-related amyloidosis // Semin Dial. – 1996. – N 9. – Р. 360-369.

29. Varela M.P., Kimmel P.L., Phillips T.M. et al. Biocompatibility of hemodialysis membranes: interrelations between plasma complement and cytokine levels // Blood Purif. – 2001. – N 19. – Р. 370-379.

30. Zingraff J.J., Noel L.H., Bardin T., Atienza C., Zins B., Drueke T.B., Kuntz D. Beta 2-microglobulin amyloidosis in chronic renal failure // N. Engl J. Med. – 1990. – N 323. – Р. 1070-1071.