Prevalence and risk factors of erythropoiesis stimulating agents hyporesponsiveness in chronic hemodialysis patients attending nephrology center of Benghazi
DOI:
https://doi.org/10.54361/LJM18.12Keywords:
ESA hyporesponsiveness, hemodialysis, , risk factorsAbstract
Background: Anemia is quite prevalent in end stage renal disease patients. Despite availability of different forms of erythropoiesis stimulating agents, many end stage renal disease patients are anemic according to National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative guidelines. Patient and methods: we conduct a cross sectional study between May 2022 and July 2022, targeting adult chronic hemodialysis patients, to investigate the prevalence of erythropoiesis stimulating agents hyporesponsiveness, to assess if patients are receiving the appropriate weight-based dosing of these agents, and to identify additional risk factors behind inadequate response to therapy.390 end stage renal disease patients are receiving chronic hemodialysis at nephrology center of Benghazi. Incident hemodialysis patients, patients with other hematological disease or with malignancy are excluded. Finally, 150 patients met the inclusion criteria and enrolled in the study. Results: 100 (66.7%) are male, and 50 (33.3%) are females. Age is 50.6 ±13.2 years. Erythropoiesis stimulating agents hyporesponsiveness is prevalent in chronic hemodialysis patients, 130 (86.7%) patients are anemic as their Hb levels were <11 g/dl, while only 20 (13.3%) patients have Hb levels of >/=11g/dl. There is a significant relationship between gender and ESA response, as hyporesponsiveness is more observed in male patients (P < .005). We find that 105 (70%) patients are receiving an appropriate weight-based dose, while only 45 (30%) patients were giving an inappropriate dose. When the relationship between ESA dosing and patients' response to ESA is examined, we find, that despite receiving the appropriate dose, 90 (60%) patients are ESA hyporesponsive, while only 15 (10%) are responsive to the appropriate weight-based dose. However, no statistical association is found between ESA hyporesponsiveness and age or weekly hours of dialysis. Conclusion: despite receiving an appropriate dosage of ESA, our study population shows high prevalence of ESA hyporesponsive anemic state. New strategies should be applied to detect risk factors and adopt therapeutic measures to reduce its high prevalence in hemodialysis population.
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References
Locatelli F, Bárány P, Covic A, et al. Kidney Disease: Improving Global Outcomes guidelines on anaemia management in chronic kidney disease: a European Renal Best Practice position statement. Nephrol Dial Transplant. 2013;28(6):1346-1359.
Santos EJF, Dias RSC, Lima JFB, Salgado Filho N, Miranda Dos Santos A. Erythropoietin Resistance in Patients with Chronic Kidney Disease: Current Perspectives. Int J Nephrol Renovasc Dis. 2020;13:231-237.
KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis. 2007;50(3):471-530.
Ma JZ, Ebben J, Xia H, Collins AJ. Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol. 1999;10(3):610-619
Sibbel SP, Koro CE, Brunelli SM, Cobitz AR. Characterization of chronic and acute ESA hyporesponse: a retrospective cohort study of hemodialysis patients. BMC Nephrol. 2015; 16:144.
Drozdz, M., Weigert, A., Silva, F. et al. Achievement of renal anemia KDIGO targets by two different clinical strategies – a European hemodialysis multicenter analysis. BMC Nephrol 2019;20(5)
Alsaeiti K, Hamedh M, Albarasi S, et al. Current clinical situation of Hemodialysis Patients in Nephrology Center, Benghazi, Libya. Journal of The Egyptian Society of Nephrology and Transplantation. 2021;21(1):43.
Wu HHL, Chinnadurai R. Erythropoietin-Stimulating Agent Hyporesponsiveness in Patients Living with Chronic Kidney Disease. Kidney Dis (Basel). 2022;8(2):103-114
Jiacong Luo, Donna E. Jensen, Bradley J. Maroni, et al. Spectrum and Burden of Erythropoiesis-Stimulating Agent Hyporesponsiveness Among Contemporary Hemodialysis Patients. Am J Kidney Dis. 2016;68(5):763-771
Henry H.L. Wua, b Rajkumar Chinnadura. Erythropoietin-Stimulating Agent Hyporesponsiveness in Patients Living with Chronic Kidney Disease. Kidney Dis 2022;8:103–114
Kamal A, Rabea A, Ragheb A, Emara M. Predictors of erythropoietin hyporesponsiveness in chronic hemodialysis patients. Menoufia Medical Journal. 2020;33(1):105.
Alemu B, Techane T, Dinegde NG, Tsige Y. Prevalence of Anemia and Its Associated Factors Among Chronic Kidney Disease Patients Attending Selected Public Hospitals of Addis Ababa, Ethiopia: Institutional-Based Cross-Sectional Study. Int J Nephrol Renovasc Dis. 2021;14:67-75.
Bae MN, Kimn SH, Kin YO, et al. Association of erythropoietinstimulating agent responsiveness with mortality in hemodialysis and peritoneal dialysis patients. PLoS One. 2015;10(11): e0143348
Elton Jonh Freitas Santos, Raimunda Sheyla Carneiro Dias, Janielle Ferreira de Brito Lima. Erythropoietin Resistance in Patients with Chronic Kidney Disease: Current Perspectives. International Journal of Nephrology and Renovascular Disease 2020:13
Ryu SR, Park SK, Jung JY et al. The prevalence and management of anemia in chronic kidney disease patients: result from the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD). J Korean Med Sci 2017; 32: 249–256
Marie Evans, Hannah Bower , Elinor Cockburn, et al. Contemporary management of anaemia, erythropoietin resistance and cardiovascular risk in patients with advanced chronic kidney disease: a nationwide analysis. Clinical Kidney Journal, 2020, vol. 13, no. 5, 821–827
Rossert J, Gassmann-Mayer C, Frei D, McClellan W. Prevalence and predictors of epoetin hyporesponsiveness in chronic kidney disease patients. Nephrol Dial Transplant. 2007;22(3):794-800.
Luo J, Jensen DE, Maroni BJ, et al. Spectrum and burden of erythropoiesis-stimulating agent hyporesponsiveness among contemporary hemodialysis patients. Am J Kidney Dis. 2016;68(5):763-771.
Scott P. Sibbel, Carol E. Koro, Steven M. Brunelli, et al. Characterization of chronic and acute ESA hyporesponse: a retrospective cohort study of hemodialysis patients. BMC Nephrology (2015) 16:144
Locatelli F, Andrulli S, Memoli B, et al. Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients. Nephrol Dial Transplant. 2006;21(4):991-998.
Ingrasciotta Y, Lacava V, Marcianò I, et al. In search of potential predictors of erythropoiesis-stimulating agents (ESAs) hyporesponsiveness: a population-based study [published correction appears in BMC Nephrol. 2020 Jul 9;21(1):262]. BMC Nephrol. 2019;20(1):359.
NKF-KDOQI Clinical Practice Guidelines (2021) National Kidney Foundation. Available at: https://www.kidney.org/professionals/guidelines. Last Accessed: April 30, 2023
El-Kannishy GM, Megahed AF, Tawfik MM, et al. Obesity may be erythropoietin dose-saving in hemodialysis patients. Kidney Res Clin Pract. 2018;37(2):148-156.
Rafael Pe´rez-Garcı´a , Javier Varas , Alejandro Cives, et al. Increased mortality in haemodialysis patients administered high doses of erythropoiesis-stimulating agents: a propensity score-matched analysis. Nephrol Dial Transplant (2018) 33: 690–699
Yusuke Sakaguchi , Takayuki Hamano, Atsushi Wada, et al. Types of Erythropoietin-Stimulating Agents and Mortality among Patients Undergoing Hemodialysis. JASN. 2019;30: 1037–1048.
Kanbay M, Perazella MA, Kasapoglu B, Koroglu M, Covic A. Erythropoiesis stimulatory agent- resistant anemia in dialysis patients: review of causes and management. Blood Purif. 2010;29(1):1-12
Kalantar-Zadeh K, Lee GH, Miller JE, et al. Predictors of hyporesponsiveness to erythropoiesis-stimulating agents in hemodialysis patients. Am J Kidney Dis. 2009;53(5):823-834).
Marisa Roldão, Rui Duarte , Rachele Escoli, et al. Predictors of hyporesponsiveness to erythropoietin in prevalent hemodialysis patients and its association with mortality. Port J Nephrol Hypert 2022; 36(1): 35-39
Wish JB. Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol. 2006;1 Suppl 1:S4-S8.
Ning, S, Zeller, MP, Management of iron deficiency. Hematology Am Soc Hematol Educ Program 2019; 2019 (1): 315–322.
Samavat, Shiva et al. “Factors Contributing to Erythropoietin Hyporesponsiveness Among Hemodialysis Patients: A Cross-Sectional Multicenter Study.” Nephro-urology monthly 9 (2017): DOI: 10.5812/numonthly.45003
DeVita MV, Frumkin D, Mittal S, Kamran A, Fishbane S, Michelis MF. Targeting higher ferritin concentrations with intravenous iron dextran lowers erythropoietin requirement in hemodialysis patients. Clin Nephrol. 2003;60(5):335-340
Locatelli F, Del Vecchio L, Pozzoni P, Andrulli S. Dialysis adequacy and response to erythropoiesis-stimulating agents: what is the evidence base?. Semin Nephrol. 2006;26(4):269-274.
Johnson DW, Pollock CA, Macdougall IC. Erythropoiesis-stimulating agent hyporesponsiveness. Nephrology (Carlton). 2007;12(4):321-330.
Motoko Tanaka, Hirotaka Komaba, Masafumi Fukagawa. Emerging Association Between Parathyroid Hormone and Anemia in Hemodialysis Patients. Therapeutic Apheresis and Dialysis 2018; 22(3):242–245
Chen L, Ling YS, Lin CH, He JX, Guan TJ. High Dose ESAs Are Associated with High iPTH Levels in Hemodialysis Patients with End-Stage Kidney Disease: A Retrospective Analysis. Front Public Health. 2015; 3:258.
Cozzolino M. CKD-MBD KDIGO guidelines: how difficult is reaching the 'target'?. Clin Kidney J. 2018;11(1):70-72
Mandolfo S, Malberti F, Farina M, et al. Parathyroidectomy and response to erythropoietin therapy in anaemic patients with chronic renal failure. Nephrol Dial Transplant. 1998;13(10):2708-2709.
Lee CT, Chou FF, Chang HW, et al. Effects of parathyroidectomy on iron homeostasis and erythropoiesis in hemodialysis patients with severe hyperparathyroidism. Blood Purif. 2003;21(6):369-375.
Neves PL, Triviño J, Casaubon F, et al. Elderly patients on chronic hemodialysis with hyperparathyroidism: increase of hemoglobin level after intravenous calcitriol. Int Urol Nephrol. 2006;38(1):175-177.
Afsar B. The relationship between depressive symptoms and erythropoietin resistance in stable hemodialysis patients with adequate iron stores. Int J Artif Organs. 2013;36(5):314-319.
Kalantar-Zadeh K, McAllister CJ, Lehn RS, Lee GH, Nissenson AR, Kopple JD. Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients. Am J Kidney Dis. 2003;42(4):761-773.
Rattanasompattikul M, Molnar MZ, Zaritsky JJ, et al. Association of malnutrition-inflammation complex and responsiveness to erythropoiesis-stimulating agents in long-term hemodialysis patients. Nephrol Dial Transplant. 2013;28(7):1936-1945.
Tomoaki Takata, Yukari Mae, Kentaro Yamada, et al. Skeletal muscle mass is associated with erythropoietin response in hemodialysis patients. BMC Nephrology (2021) 22:134
Hyang Yun Lee, Suk-Won Suh, Jin Ho Hwang, et al. Responsiveness to an erythropoiesis-stimulating agent is correlated with body composition in patients undergoing chronic hemodialysis. Front. Nutr. 9:1044895
Ahmed Rabea, Ahmed Ragheb, Mahmoud Emara, et al. Predictors of erythropoietin hyporesponsiveness in chronic hemodialysis patients. Menoufia Medical Journal 2020, 33:105–109
Qureshi IZ, Abid K, Ambreen F, Qureshi AL. Angiotensin converting enzyme inhibitors impair recombinant human erythropoietin induced erythropoiesis in patients with chronic renal failure. Saudi Med J. 2007;28(2):193-196.
Ertürk S, Ateş K, Duman N, Karatan O, Erbay B, Ertuğ E. Unresponsiveness to recombinant human erythropoietin in hemodialysis patients: possible implications of angiotensin-converting enzyme inhibitors. Nephrol Dial Transplant. 1996;11(2):396-397
Vlahakos DV, Balodimos C, Papachristopoulos V, Vassilakos P, Hinari E, Vlachojannis JG. Renin-angiotensin system stimulates erythropoietin secretion in chronic hemodialysis patients. Clin Nephrol. 1995;43(1):53-59.
Hitesh H. Shah, Nupur N. Uppal, and Steven Fishbane. Inflammation and Erythropoiesis-Stimulating Agent Hyporesponsiveness: A Critical Connection. Kidney Med Vol 2 | Iss 3 | May/June 2020
Ryan Gupta, Karen Woo, Jeniann A. Yi. Epidemiology of end-stage kidney disease. Seminars in Vascular Surgery. 2021;34 (1): 71-78.
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