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Impact of anemia treatment with methoxy polyethylene glycol-epoetin beta on polymorphonuclear cells apoptosis in predialysis patients with chronic kidney disease

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Abstract

Background

Some data in literature indicate increased apoptosis of polymorphonuclear cells (PMNs) in chronic kidney disease (CKD), what seems to be connected with anemia. Erythropoiesis-stimulating agents, used in anemia treatment in CKD may affect cells apoptosis. Aim of this study was to investigate impact of anemia treatment with methoxy polyethylene glycol-epoetin beta (CERA) on PMNs apoptosis in predialysis patients with CKD.

Methods

Percentage of early and late apoptotic PMNs was measured by flow cytometry based on annexin V and propidium iodide binding. CD90 (Fas), CD95L (FasL), CD16 and CD11b expression on PMNs were evaluated by flow cytometry after incubation with respective monoclonal antibody.

Results

Percentage of PMNs in early and late apoptosis in CKD patients before CERA treatment was significantly higher to control group, which was accompanied by significantly higher Fas and Fas-L expression and significantly lower expression of CD16. CERA treatment downregulated significantly percentage of early, apoptotic PMNs but percentage of late apoptotic cells did not change and was still significantly higher to control group. In all investigated groups we observed a significant negative correlation between hemoglobin concentration and percentage of apoptotic PMNs, as well as Fas and FasL expression and significant positive correlation between Hb and CD16 expression.

Conclusions

Our results indicate that PMNs apoptosis is increased in predialysis patients with CKD and anemia treatment with CERA may diminish readiness of PMNs to undergo apoptosis. This antiapoptotic impact of anemia treatment with CERA seems to concern early apoptotic PMNs before they undergo to late, irreversible stage of apoptosis.

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References

  1. Pereira WO, Amarante-Mendes GP. Apoptosis: a programme of cell death or cell disposal? Scand J Immunol 2011;73(5):401–7.

    Article  CAS  Google Scholar 

  2. Sanderberg C, Suassuna P, Cruz Andreoli MC, Watanabe R, Dalboni MA, Manfredi SR, et al. Effects of uremia and dialysis modality on polymorphonuclear cell apoptosis and function. Nephrol Dial Transplant 2006;21(1):160–5.

    Article  Google Scholar 

  3. Jaber BL, Cendoroglo M, Balakrishnan VS, Perianayagam MC, King AJ, Pereira BJ. Apoptosis of leukocytes: basic concepts and implications in uremia. Kidney Int 2001;59(Suppl. 78s):S197–205.

    Article  Google Scholar 

  4. Majewska E, Baj Z, Sułowska Z, Rysz J, Luciak M. Effects of uraemia and haemodialysis on neutrophil apoptosis and expression of apoptosis-related proteins. Nephrol Dial Transplant 2003;18(12):2582–8.

    Article  CAS  Google Scholar 

  5. D’Intini V, Bordoni V, Fortunato A, Galloni E, Carta M, Galli F, et al. Longitudinal study of apoptosis in chronic uremic patients. Semin Dial 2003;16(6):467–73.

    Article  Google Scholar 

  6. Sato M, Konuma T, Yanagisawa N, Haziuka H, Asakura H, Nakashima Y. Fas-Fas ligand system in the peripheral blood of patients with renal diseases. Nephron 2000;85(2):107–13.

    Article  CAS  Google Scholar 

  7. Chen NH, Cheong KA, Kim Ch, Noh M, Lee AY. Glucosamine induces activated T cell apoptosis through reduced T cell receptor. Scand J Immunol 2013;78(1): 17–27.

    Article  CAS  Google Scholar 

  8. Mikhail A, Covic A, Goldsmith D. Stimulating erythropoiesis: future perspectives. Kidney Blood Press Res 2008;31(4):234–46.

    Article  CAS  Google Scholar 

  9. Weiner DE, Tighiouart H, Vlagopoulos PT, Griffith JL, Salem DN, Levey AS, et al. Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease. J Am Soc Nephrol 2005;16(6):1803–10.

    Article  Google Scholar 

  10. Ofsthun N, Labrecgue J, Lacson E, Keen M, Lazarus JM. The effects of higher haemoglobin levels on mortality and hospitalisation in haemodialysis patients. Kidney Int 2003;63(5):1908–14.

    Article  Google Scholar 

  11. Bahlman FH, Kielstein JT, Haller H, Fliser D. Erythropoietin and progression of CKD. Kidney Int 2007;72(Suppl. 107s):S21–5.

    Article  Google Scholar 

  12. Gouva C, Nikolopoulos P, Ioannidis JP, Siamopoulos KC. Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kidney Int 2004;66(2):753–60.

    Article  Google Scholar 

  13. Katavetin P, Tungsanga K, Eiam-Ong S, Nangaku M. Antioxidative effects of erythropoietin. Kidney Int 2007;72(Suppl. 107s):S10–5.

    Article  Google Scholar 

  14. Macdougall IC, Walker R, Provenzano R, de Alvaro F, Locay HR, Nader PC, et al., ARCTOS Investigators. C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial. Clin J Am Soc Nephrol 2008;3(2):337–47.

    Article  Google Scholar 

  15. Kessler M, Martinez-Castelao A, Siamopoulos KC, Villa G, Spinowitz B, Dougherity FC, et al. C.E.R.A. once every 4 weeks in patients with chronic kidney disease not on dialysis: the ARCTOS extension study. Hemodial Int 2010;14(2): 233–9.

    Google Scholar 

  16. Varmes I, Haanen C, Steffens-Nakken H, Reutelingsperger CA. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labeled annexin V. J Immunol Methods 1995;184(1):39–51.

    Article  Google Scholar 

  17. Nusbaum P, Lainé C, Seveau S, Lesavre P, Halbwachs-Mecarelli L. Early membrane events in polymorphonuclear cell (PMN) apoptosis: membrane blebbing and vesicle release, CD43 and CD16 down-regulation and phosphatidylserine externalization. Biochem Soc Trans 2004;32(Pt3):477–9.

    Article  CAS  Google Scholar 

  18. Sela S, Shurtz-Swirski R, Cohen-Mazor M, Mazor R, Chezar J, Shapiro G, et al. Primed peripheral polymorphonuclear leukocyte: a culprit underlying chronic low-grade inflammation and systemic oxidative stress in chronic kidney disease. J Am Soc Nephrol 2005;16(8):2431–8.

    Article  CAS  Google Scholar 

  19. Martin FL, McKie PM, Cataliotti A, Sangaralingham SJ, Korinek J, Huntley BK, et al. Experimental mild renal insufficiency mediates early cardiac apoptosis, fibrosis and diastolic dysfunction: a kidney-heart connection. Am J Physiol Regul Integr Comp Physiol 2012;302(2):292–9.

    Article  Google Scholar 

  20. Yilmaz MI, Sonmez A, Ortiz A, Saglam M, Kilic S, Eyileten T, et al. Soluble TWEAK and PTX3 in nondialysis CKD patients: impact on endothelial dysfunction and cardiovascular outcomes. Clin J Am Soc Nephrol 2011;6(4):785–92.

    Article  CAS  Google Scholar 

  21. Petronilli V, Penzo D, Scorrano L, Bernardi P, Di Lisa F. The mitochondrial permeability transition, release of cytochrome c and cell death, Correlation with the duration of pore openings in situ. J Biol Chem 2001;276(15): 12030–34.

    Article  CAS  Google Scholar 

  22. Gustafsson AB, Gottlieb RA. Bcl-2 family members and apoptosis, taken to heart. Am J Physiol Cell Physiol 2007;292(1):C45–51.

    Article  CAS  Google Scholar 

  23. Rossert J, Froissart M. Role of anemia in progression of chronic kidney disease. Semin Nephrol 2006;26(4):283–9.

    Article  CAS  Google Scholar 

  24. Nangaku M, Fliser D. Erythropoiesis-stimulating agents: past and future. Kidney Int 2007;72(Suppl. 107s):S1–3.

    Article  Google Scholar 

  25. Cassis P, Gallon L, Benigni A, Mister M, Pezzotta A, Solini S, et al. Erythropoietin, but not the correction of anemia alone, protects from chronic kidney allograft injury. Kidney Int 2012;81(9):903–18.

    Article  CAS  Google Scholar 

  26. Chatterjee PK. Pleiotropic renal actions of erythropoietin. Lancet 2005; 365(9474):1890–2.

    Article  CAS  Google Scholar 

  27. Kowalczyk M, Banach M, Mikhailidis DP, Rysz J. Erythropoietin update. Med Sci Monit 2011;17(11):240–7.

    Article  Google Scholar 

  28. Lisowska KA, Debska-Slizien A, Bryl E, Rutkowski B, Witkowski JM. Erythropoietin receptor is expressed on human peripheral blood T and B lymphocytes and monocytes and is modulated by recombinant human erythropoietin treatment. Artif Organs 2010;34(8):654–62.

    CAS  PubMed  Google Scholar 

  29. Tankiewicz–Kwedlo A, Pawlak D, Domaniewski T, Buczko W. Effect of erythropoietin, 5-fluoroyracil and SN-38 on the growth of DLD-1 cells. Pharmacol Rep 2010;62(5):926–37.

    Article  CAS  Google Scholar 

  30. Rossert J, Eckardt KU. Erythropoietin receptors: their role beyond erythropoiesis. Nephrol Dial Transplant 2005;20(6):1025–8.

    Article  CAS  Google Scholar 

  31. Eto N, Wada T, Inagi R, Takano H, Shimizu A, Kato H, et al. Podocyte protection by darbepoetin: preservation of the cytoskeleton and nephrin expression. Kidney Int 2007;72(4):455–63.

    Article  CAS  Google Scholar 

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Correspondence to Piotr Bartnicki.

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Bartnicki, P., Majewska, E., Kowalczyk, M. et al. Impact of anemia treatment with methoxy polyethylene glycol-epoetin beta on polymorphonuclear cells apoptosis in predialysis patients with chronic kidney disease. Pharmacol. Rep 67, 842–845 (2015). https://doi.org/10.1016/j.pharep.2015.01.014

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  • DOI: https://doi.org/10.1016/j.pharep.2015.01.014

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