Background: The relationship between the iron indices and mortality in maintenance hemodialysis (MHD) patients has remained unclear. We performed a retrospective, observational cohort study to investigate the relationships between serum ferritin levels and mortality in MHD patients. Methods: MHD outpatients (n = 150) were followed up for a median period of 49 months. Their ESA and low-dose iron supplement dosages were adjusted to maintain their hemoglobin (Hb) concentrations in the 10 - 11 g/dl range in accordance with Japanese guidelines. The Kaplan-Meier method, log-rank tests, and Cox proportional hazards models were used to perform the statistical analyses. The patients were divided into 3 groups according to their serum ferritin levels: a serum ferritin < 50 ng/ml group; a 50 - 100 ng/ml group; and a > 100 ng/ml group. Results: During the median follow-up period of 49 months, there were 55 deaths. The multivariate analysis showed no significant associations between the ferritin level groups and all-cause mortality or cardiovascular (CV) events, and the Kaplan-Meier analysis showed no significant differences among the 3 ferritin level groups in all-cause mortality and CV event rates. However, the multivariate analysis revealed that age, CRP level and a history of previous CV disease were independently associated with all-cause mortality, while diabetes, previous CV disease, and iron administration were independently associated with CV events. Conclusion: The results of this study revealed no significant associations of MHD patients between the ferritin ranges and all-cause mortality or CV events. Thus, the adverse clinical outcomes in these patients were independently associated with other markers and not with their serum ferritin levels.
KeywordsAnemiaFerritinHemodialysisMortality
Masakane, I., Taniguchi, M.., Nakai, S., Tsuchida, K., Goto, S., Wada, A., Ogata, S., Hasegawa, T., Hamano, T., Hanafusa, N., Hoshino, J., Minakuchi, J. and Nakamoto, H. (2018) Annual Dialysis Data Report 2015, JSDT Renal Data Registry (JRDR). Renal Replacement Therapy, 4, 19.
Pisoni, R.L., Bragg-Gresham, J.L., Young, E.W., Akizawa, T., Asano, Y., Locatelli, F., Bommer, J., Cruz, J.M., Kerr, P.G., Mendelssohn, D.C., Held, P.J. and Port, F.K. (2004) Anemia Management and Outcomes from 12 Countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). American Journal of Kidney Diseases, 44, 94-111. https://doi.org/10.1053/j.ajkd.2004.03.023
Nakanishi, T., Hasuike, Y., Otaki, Y., Nanami, M. and Kuragano, T. (2015) Dysregulated Iron Metabolism in Patients on Hemodialysis. Contribution to Nephrology, 185, 22-31.
Yamamoto, H., Nishi, S., Tomo, T., Masakane, I., Saito, K., Nangaku, M., Hattori, M., Suzuki, T., Morita, S., Ashida, A., Ito, Y., Kuragano, T., Komatsu, Y., Sakai, K., Tsubakihara, Y., Tsuruya K., Hayashi, T., Hirakata, H. and Honda, H. (2017) 2015 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease. Renal Replacement Therapy, 3, 36. https://doi.org/10.1186/s41100-017-0114-y
Madore, F., White, C.T., Foley, R.N., Barrett, B.J., Moist, L.M., Klarenbach, S.W., Culleton, B.F., Tonelli, M., Manns, B.J., Canadian Society of Nephrology. (2008) Clinical Practice Guidelines for Assessment and Management of Iron Deficiency. Kidney International Supplement, 110, S7-S11. https://doi.org/10.1038/ki.2008.269
Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group (2012) KDIGO Clinical Practice Guidelines for Anemia in Chronic Kidney Disease. Kidney International Supplement, 2, 279-335.
Kliger, A.S., Foley, R.N., Goldfarb, D.S., Goldstein, S.L., Johansen, K., Singh, A. and Szczech, L. (2013) KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD. American Journal of Kidney Diseases, 62, 849-859. https://doi.org/10.1053/j.ajkd.2013.06.008
Macginley, R., Walker, R. and Irving, M. (2013) KHA-CARI Guideline: Use of Iron in Chronic Kidney Disease Patients. Nephrology (Carlton), 18, 747-749. https://doi.org/10.1111/nep.12139
Locatelli, F., Barany, P., Covic, A., De Francisco, L., Goldsmith, D., Horl, W., London, G., Vanholder, R., Van Biesen, W., ERA-EDTA ERBP Advisory Board. (2013) Kidney Disease: Improving Global Outcomes Guidelines on Anaemia Management in Chronic Kidney Disease: A European Renal Best Practice Position Statement. Nephrology Dialysis Transplantation, 28, 1346-1359. https://doi.org/10.1093/ndt/gft033
Karaboyas, A., Zee, J., Morgenstern, H., Nolen, J.G., Hakim, R., Kalantar-Zadeh, K., Zager, P., Pisoni, R.L., Port, F.K. and Robinson, B.M. (2015) Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing. Clinical Journal of American Society of Nephrology, 10, 1814-1821. https://doi.org/10.2215/CJN.02600315
Kuragano, T., Matsumura, O., Matsuda, A., Hara, T., Kiyomoto, H., Murata, T., Kitamura, K., Fujimoto, S., Hase, H., Joki, N., Fukatsu, A., Inoue, T., Itakura I. and Nakanishi, T. (2014) Association between Hemoglobin Variability, Ferritin Levels, and Adverse Events/Mortality in Maintenance Hemodialysis Patients. Kidney International, 86, 845-854. https://doi.org/10.1038/ki.2014.114
Park, K.S., Ryu, G.W., Jhee, J.H., Kim, H.W., Park, S., Lee, S.A., Kwon, Y.E., Kim, Y.L., Ryu, H.J., Lee, M.J., Han, S.H., Yoo, T.H., Kim, Y.L., Kim, Y.S., Yang, C.W., Kim, N.H., Kang, S.W. and Park, J.T. (2015) Serum Ferritin Predicts Mortality Regardless of Inflammatory and Nutritional Status in Patients Starting Dialysis: A Prospective Cohort Study. Blood Purification, 40, 209-217. https://doi.org/10.1159/000438819
Kawaguchi, T., Tong, L., Robinson, B.M., Sen, A., Fukuhara, S., Kurokawa, K., Canaud, B., Lamiere, N., Port, F.K. and Pisoni, R.L. (2011) C-Reactive Protein and Mortality in Hemodialysis Patients: The Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephron Clinical Practice, 117, c167-c178. https://doi.org/10.1159/000320116
Alberti, K.G. and Zimmet, P.Z. (1998) Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications. Part 1: Diagnosis and Classification of Diabetes Mellitus Provisional Report of a WHO Consultation. Diabetic Medicine, 15, 539-553. https://doi.org/10.1002/(SICI)1096-9136(199807)15:7%3C539::AID-DIA668%3E3.0.CO;2-S
Tsubakihara, Y., Nishi, S., Akiba, T., Hirakata, H., Iseki, K., Kubota, M., Kuriyama, S., Komatsu, Y., Suzuki, M., Nakai, S., Hattori, M., Babazono, T., Hiramatsu, M., Yamamoto, H., Bessho, M. and Akizawa, T. (2010) 2008 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease. Therapeutic Apheresis and Dialysis, 14, 240-275. https://doi.org/10.1111/j.1744-9987.2010.00836.x
Saito, A., Onuki, T., Echida, Y., Otsubo, S. and Nitta, K. (2014) Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Hemodialysis Patients. International Journal of Clinical Medicine, 5, 1102-1110. https://doi.org/10.4236/ijcm.2014.517141
Otterstad, J.E., Froeland, G., St John Sutton, M. and Holme, I. (1997) Accuracy and Reproducibility of Biplane Two-Dimensional Echocardiographic Measurements of Left Ventricular Dimensions and Function. European Heart Journal, 18, 507-513. https://doi.org/10.1093/oxfordjournals.eurheartj.a015273
Hasuike, Y., Nonoguchi, H., Tokuyama, M., Ohue, M., Nagai, T., Yahiro, M., Nanami, M., Otaki, Y. and Nakanishi, T. (2010) Serum Ferritin Predicts Prognosis in Hemodialysis Patients: The Nishinomiya Study. Clinical and Experimental Nephrology, 14, 349-355. https://doi.org/10.1007/s10157-010-0288-x
Shoji, T., Niihara, K., Fukuma, S., Fukuhara, S., Akizawa, T. and Inaba, M. (2017) Both Low and High Serum Ferritin Levels Predict Mortality Risk in Hemodialysis Patients without Inflammation. Clinical and Experimental Nephrology, 21, 685-693. https://doi.org/10.1007/s10157-016-1317-1
Ogawa, C., Tsuchiya, K., Kanda, F. and Maeda, T. (2014) Low Levels of Serum Ferritin Lead to Adequate Hemoglobin Levels and Good Survival in Hemodialysis Patients. American Journal of Nephrology, 40, 561-570. https://doi.org/10.1159/000370317
Wish, J.B. (2006) Assessing Iron Status: Beyond Serum Ferritin and Transferrin Saturation. Clinical Journal of American Society of Nephrology, Suppl 1, S4-S8. https://doi.org/10.2215/CJN.01490506
Ma, L. and Zhao, S. (2017) Risk Factors for Mortality in Patients Undergoing Hemodialysis: A Systematic Review and Meta-Analysis. International Journal of Cardiology, 238, 151-158. https://doi.org/10.1016/j.ijcard.2017.02.095