The relationship between the dose of continuous erythropoietin receptor activator and oxidative stress in hemodialysis patients

Keywords: hemodialysis patients,continuous erythropoietin receptor activator, oxidative stress

Abstract

At present, there have been no reports on the dose-dependent effects of continuous erythropoietin receptor activator(CERA) therapy on oxidative stress and red blood cell membrane lipid peroxidation parameters in hemodialysis (HD) patients.

The aim of our work was to evaluate whether the dose of CERA treatment affected lipid peroxidation and antioxidant system in HD patients.

Methods. 38 HD patients were included in this single-center cross-sectional observational study. The study protocol was approved by a local Ethics Committee and all patients provided signed informed consent. The patients were stratified into quartiles (≤25% and ≥75%) according to the average dose of continuous erythropoietin receptor activator (CERA) and grouped in the following way: Group I (> 6 months of CERA treatment in a low dosage ≤ 50 μg/month, n = 20) and Group II (> 6 months of CERA treatment in a high dosage ≥ 125 μg/month, n = 18). Along with the standard diagnostic methods, we defined the content of malondialdehyde levels in the serum (MDAs) and erythrocytes (MDAe) spectrophotometrically as an indicator of lipid peroxidation. Such parameters as the concentration of ceruloplasmin (CP) and transferrin (TR) in the blood and total peroxidase activity (TPA) in erythrocyte were studied as the indicators of antioxidant system. In addition, we calculated the percentage of hemolysis, the RBC membrane permeability and oxidation coefficient.

Results. We obtained heterogeneous results in assessing oxidative stress parameters. The significantly higher levels of CP (p = 0.007) and TR (p = 0.0003) were found in the patients treated with a high dosage CERA. TPA activity in erythrocyte in the patients of Group II was statistically higher compared to Group I (p = 0.02). Moreover, we determined a statistically high percentage of hemolysis (p = 0.03) and RBC membrane permeability (p ˂ 0.0001) in the patients who were treated with CERA in a dose ≥ 125 μg/month compared to other patients. Using the probit regression model, we established the dose-dependent effect of CERA on the level of RBC membranes permeability: χ2 = 21; p = ˂ 0.0001.

Conclusions. We demonstrated that administration of CERA in a dose more 125 μg/month improved the antioxidant status in HD patients. But, at the same time, it increased the hemolysis and RBC membranes permeability. Our preliminary data pointing to the dose-dependent effect of CERA on the RBC membrane lipid peroxidation parameters require further confirmation.

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References

Liakopoulos V, Roumeliotis S, Gorny X, Dounousi E, Mertens PR. Oxidative Stress in Hemodialysis Patients: A Review of the Literature. Oxidative Medicine and Cellular Longevity. 2017;2017:3081856. doi:10.1155/2017/3081856.

Tharmaraj D, Kerr  PG. Haemolysis in haemodialysis. Nephrology. 2017;22: 838-847. doi:10.1111/nep.13119  

KDIGO Clinical practice guideline for Anaemia in chronic kidney disease. Kidney Int Suppl. 2012;2:279-335. doi:10.1038/kisup.2012.37

Mikhail A, Brown C, Williams JA, et al. Renal association clinical practice guideline on Anaemia of Chronic Kidney Disease. BMC Nephrology. 2017;18:345. doi:10.1186/s12882-017-0688-1.

Khalil SKM, Amer HA, Behairy AM, Warda M. Oxidative stress during erythropoietin hyporesponsiveness anemia at end stage renal disease: Molecular and biochemical studies. Journal of Advanced Research. 2016;7(3):348-358. doi:10.1016/j.jare.2016.02.004.

Fassett RG, Driver R, Healy H, et al. Comparison of markers of oxidative stress, inflammation and arterial stiffness between incident hemodialysis and peritoneal dialysis patients – an observational study. BMC Nephrology. 2009;10:8. doi:10.1186/1471-2369-10-8.

Siems W., Carluccio F., Radenkovic S., Grune T., Hampl H. Oxidative stress in renal anemia of hemodialysis patients is mitigated by epoetin treatment. Kidney & Blood Pressure Research. 2005;28(5-6):295–301. doi: 10.1159/000090184.

Dimitrijevic ZM, Cvetkovic TP, Djordjevic VM, et al. How the Duration Period of Erythropoietin Treatment Influences the Oxidative Status of Hemodialysis Patients. International Journal of Medical Sciences. 2012;9(9):808-815. doi:10.7150/ijms.4910.

Pawlak K1, Pawlak D, Mysliwiec M. Long-term erythropoietin therapy does not affect endothelial markers, coagulation activation and oxidative stress in haemodialyzed patients. Thromb Res. 2007;120(6):797-803. doi: 10.1016/j.thromres.2007.02.004

Mircescu G1, Căpuşă C, Stoian I, Mărăcine M, Muscurel C, Gârneată L, Bărbulescu C. Influence of epoietinum therapy on the oxidative stress in haemodialysis patients. Nephron Clin Pract. 2005;100(4):126-32. doi: 10.1159/000085441

Saglimbene VM1, Palmer SC, Ruospo M, Natale P, Craig JC, Strippoli GF. Continuous erythropoiesis receptor activator (CERA) for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2017 Aug 7;8:CD009904. doi: 10.1002/14651858.CD009904.pub2.

Likuvannia khvorykh na z khronichnu khvorobu nyrok V HD stadii. Adaptovana klinichna nastanova, zasnovana na dokazakh ta unifikovani klinichni protokoly. – K. : «Polihraf plius», 2016. – 228 s.

Korol LV, Mygal LYa, Stepanova NM. Intensity of oxidative stress and activity of angiotensin converting enzyme in blood of patients with uncomplicated pyelonephritis. Ukr.Biochem.J. 2017;89(2):99-105. doi: 10.15407/ubj89.02.099

 Janatpour K, Denning L, Nelson K, et al. Comparison of X-ray vs. gamma irradiation of CPDA-1 red cells. Vox Sang. 2005;89:215–219. doi: 10.1111/j.1423-0410.2005.00699.

 Kamyishnikov VS. Spravochnik po klinicheskoy laboratornoy diagnostike: V 2t. Minsk : Belarus; 2002. 463 s.

Bartnicki P, Fijałkowski P, Majczyk M, Błaszczyk J, Banach M, Rysz J. Effect of methoxy polyethylene glycol-epoetin beta on oxidative stress in predialysis patients with chronic kidney disease. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2013;19:954-959. doi:10.12659/MSM.884024.

Sosa M, Balk ME, Lau J, Liangos O, Balakrishnan VS, Madias NE, Pereira BJG, Jaber BL. A systematic review of the effect of the Excebrane dialyser on biomarkers of lipid peroxidation. Nephrology Dialysis Transplantation. 2006; 21(10):2825–2833. https://doi.org/10.1093/ndt/gfl376

Müller C, Eisenbrand G, Gradinger M, Rath T, Albert FW, Vienken J, Singh R, Farmer PB, Stockis J-P, Janzowski C. Effects of hemodialysis, dialyser type and iron infusion on oxidative stress in uremic patients, free radical research. 2004; 38(10):1093-1100, doi: 10.1080/10715760400011452

Tonon J, Guarnier FA, Cecchini AL, Cecchini R. Anemia associated with extraerythrocytic oxidative stress damage mediated by neutrophil superoxide anion production in chronic renal failure patients undergoing hemodialysis. Pathophysiology. 2012; 19(4):261-8. doi: 10.1016/j.pathophys.2012.07.006.

Katavetin P1, Tungsanga K, Eiam-Ong S, Nangaku M. Antioxidative effects of erythropoietin. Kidney Int Suppl. 2007;(107):10-5. doi: 10.1038/sj.ki.5002482.

Ahmadiasl N, Banaei S, Alihemmati A. Combination Antioxidant Effect of Erythropoietin and Melatonin on Renal Ischemia-Reperfusion Injury in Rats. Iranian Journal of Basic Medical Sciences. 2013;16(12):1209-1216. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933796/

Bamgbola OF. Pattern of resistance to erythropoietin-stimulating agents in chronic kidney disease. Kidney International. 201;80(5):64-474. doi:10.1038/ki.2011.179

 Mohanty JG, Nagababu E, Rifkind JM. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Frontiers in Physiology. 2014;5:84. doi:10.3389/fphys.2014.00084.

Aizawa K, Kawasaki R, Tashiro Y, Shimonaka Y, Hirata M. Epoetin beta pegol for treatment of anemia ameliorates deterioration of erythrocyte quality associated with chronic kidney disease. BMC Nephrology. 2018;19:19. doi:10.1186/s12882-018-0818-4.

Gallucci MT, Lubrano R, Meloni C, Morosetti M, Manca di Villahermosa S, Scoppi P, Palombo G, Castello MA, Casciani CU. Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients. Clin Nephrol. 1999;52(4):239-45.

Tutal E, Sezer S, Bilgic A, Aldemir D, Turkoglu S, Demirel O, Ozdemir N, Haberal M. Influence of oxidative stress and inflammation on rHuEPO requirements of hemodialysis patients with CRP values "in normal range". Transplant Proc. 2007;39(10):3035-40. doi: 10.1016/j.transproceed.2007.06.090.


Abstract views: 437
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Published
2018-09-30
How to Cite
Stepanova, N., Korol, L., Novakivskyy, V., & Kolesnyk, M. (2018). The relationship between the dose of continuous erythropoietin receptor activator and oxidative stress in hemodialysis patients. Ukrainian Journal of Nephrology and Dialysis, (3(59), 18-24. https://doi.org/10.31450/ukrjnd.3(59).2018.03