Relationship Between Responsiveness to Erythropoiesis-stimulating Agent and Long-term Outcomes in Chronic Hemodialysis Patients: a Single-center Cohort Study

Overview

Journal Int Urol Nephrol

Publisher Springer

Specialty Nephrology

Date 2013 Jun 29

PMID 23807369

Citations 9

Authors

Tetsuya Ogawa

Himiko Shimizu

Ai Kyono

Masayo Sato

Tetsuri Yamashita

Kuniaki Otsuka

Kosaku Nitta

Affiliations

Soon will be listed here.

Abstract

Background: Responsiveness to erythropoietin-stimulating agent (ESA) may be associated with mortality risk in hemodialysis (HD) patients. The aim of the present study was to assess the relationship between responsiveness to ESA and long-term outcome in chronic HD patients.

Methods: Patients on HD therapy for more than 6 months were enrolled in this cohort study. The first year was used to assess the longitudinal dialysis status of patients; the subsequent years were used to assess the time-dependent risk of all-cause mortality. Hazard ratios were estimated using a Cox proportional model for the association between ESA dose and hemoglobin (Hb) level and mortality, adjusting for potential confounders. The ESA resistance index (ERI) was determined as the weekly weight-adjusted dose of ESA divided by Hb concentration. Patients were divided into three groups by tertiles of ERI.

Results: Of the 320 subjects enrolled, 105 died during the follow-up period of 70.4 ± 29.0 months. When subjects were stratified by epoetin dose and Hb level into four groups, those who had low Hb despite a high dose of epoetin were associated with the highest risk of mortality among the four groups (adjusted hazard ratio 1.86; 95 % confidence interval 1.25-2.75). These highest risk subjects had older age, lower body mass index, and lower serum levels of albumin, triglyceride, and transferring saturation. The impact of serum albumin and serum ferritin on mortality risk in an adjusted Cox proportional hazards model was in accordance with low Hb and higher ESA. There was no significant difference between the mortality risk and tertile of ERI.

Conclusions: High ESA dose and low Hb level were associated with an increased risk of all-cause mortality. However, the responsiveness to ESA estimated by ERI was not related to mortality risk. These findings suggest that the responsiveness to ESA should be evaluated by different methods in HD patients.

Citing Articles

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Synergistic deterioration of prognosis associated with decreased grip strength and hyporesponse to erythropoiesis-stimulating agents in patients undergoing hemodialysis.

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High Erythropoiesis Resistance Index Is a Significant Predictor of Cardiovascular and All-Cause Mortality in Chinese Maintenance Hemodialysis Patients.

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van den Oever F, Heetman-Meijer C, Birnie E, Vasbinder E, Swart E, Schrama Y Pharmacol Res Perspect. 2020; 8(4):e00628.

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References

Regidor D, Kopple J, Kovesdy C, Kilpatrick R, McAllister C, Aronovitz J . Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients. J Am Soc Nephrol. 2006; 17(4):1181-91. DOI: 10.1681/ASN.2005090997. View

Abe M, Okada K, Maruyama T, Maruyama N, Matsumoto K, Soma M . Relationship between erythropoietin responsiveness, insulin resistance, and malnutrition-inflammation-atherosclerosis (MIA) syndrome in hemodialysis patients with diabetes. Int J Artif Organs. 2011; 34(1):16-25. DOI: 10.5301/ijao.2011.6314. View

Smrzova J, Balla J, Barany P . Inflammation and resistance to erythropoiesis-stimulating agents--what do we know and what needs to be clarified?. Nephrol Dial Transplant. 2005; 20 Suppl 8:viii2-7. DOI: 10.1093/ndt/gfh1109. View

Johnson D, Pollock C, Macdougall I . Erythropoiesis-stimulating agent hyporesponsiveness. Nephrology (Carlton). 2007; 12(4):321-30. DOI: 10.1111/j.1440-1797.2007.00810.x. View

. II. Clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease in adults. Am J Kidney Dis. 2006; 47(5 Suppl 3):S16-85. DOI: 10.1053/j.ajkd.2006.03.011. View

Akizawa T, Pisoni R, Akiba T, Saito A, Fukuhara S, Asano Y . Japanese haemodialysis anaemia management practices and outcomes (1999-2006): results from the DOPPS. Nephrol Dial Transplant. 2008; 23(11):3643-53. PMC: 2568010. DOI: 10.1093/ndt/gfn346. View

Locatelli F, Pisoni R, Combe C, Bommer J, Andreucci V, Piera L . Anaemia in haemodialysis patients of five European countries: association with morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant. 2003; 19(1):121-32. DOI: 10.1093/ndt/gfg458. View

Chung S, Song H, Shin S, Ihm S, Park C, Kim H . Relationship between erythropoietin resistance index and left ventricular mass and function and cardiovascular events in patients on chronic hemodialysis. Hemodial Int. 2011; 16(2):181-7. DOI: 10.1111/j.1542-4758.2011.00644.x. View

Kalantar-Zadeh K, Lee G, Miller J, Streja E, Jing J, Robertson J . Predictors of hyporesponsiveness to erythropoiesis-stimulating agents in hemodialysis patients. Am J Kidney Dis. 2009; 53(5):823-34. PMC: 2691452. DOI: 10.1053/j.ajkd.2008.12.040. View

10.

Szczech L, Barnhart H, Sapp S, Felker G, Hernandez A, Reddan D . A secondary analysis of the CHOIR trial shows that comorbid conditions differentially affect outcomes during anemia treatment. Kidney Int. 2009; 77(3):239-46. PMC: 2902281. DOI: 10.1038/ki.2009.415. View

11.

Kilpatrick R, Critchlow C, Fishbane S, Besarab A, Stehman-Breen C, Krishnan M . Greater epoetin alfa responsiveness is associated with improved survival in hemodialysis patients. Clin J Am Soc Nephrol. 2008; 3(4):1077-83. PMC: 2440273. DOI: 10.2215/CJN.04601007. View

12.

Daugirdas J . Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol. 1993; 4(5):1205-13. DOI: 10.1681/ASN.V451205. View

13.

Stenvinkel P . The role of inflammation in the anaemia of end-stage renal disease. Nephrol Dial Transplant. 2001; 16 Suppl 7:36-40. DOI: 10.1093/ndt/16.suppl_7.36. View

14.

Robinson B, Joffe M, Berns J, Pisoni R, Port F, Feldman H . Anemia and mortality in hemodialysis patients: accounting for morbidity and treatment variables updated over time. Kidney Int. 2005; 68(5):2323-30. DOI: 10.1111/j.1523-1755.2005.00693.x. View

15.

Hasegawa T, Bragg-Gresham J, Pisoni R, Robinson B, Fukuhara S, Akiba T . Changes in anemia management and hemoglobin levels following revision of a bundling policy to incorporate recombinant human erythropoietin. Kidney Int. 2010; 79(3):340-6. DOI: 10.1038/ki.2010.382. View

16.

Kalantar-Zadeh K, McAllister C, Lehn R, Lee G, Nissenson A, Kopple J . Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients. Am J Kidney Dis. 2003; 42(4):761-73. DOI: 10.1016/s0272-6386(03)00915-6. View

17.

Szczech L, Barnhart H, Inrig J, Reddan D, Sapp S, Califf R . Secondary analysis of the CHOIR trial epoetin-alpha dose and achieved hemoglobin outcomes. Kidney Int. 2008; 74(6):791-8. PMC: 2902279. DOI: 10.1038/ki.2008.295. View

18.

Zhang Y, Thamer M, Stefanik K, Kaufman J, Cotter D . Epoetin requirements predict mortality in hemodialysis patients. Am J Kidney Dis. 2004; 44(5):866-76. View

19.

Locatelli F, Aljama P, Barany P, Canaud B, Carrera F, Eckardt K . Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant. 2004; 19 Suppl 2:ii1-47. DOI: 10.1093/ndt/gfh1032. View

20.

Kaysen G, Muller H, Ding J, Chertow G . Challenging the validity of the EPO index. Am J Kidney Dis. 2005; 47(1):166. DOI: 10.1053/j.ajkd.2005.09.013. View