Skip to main content
Top
Published in: Clinical and Experimental Nephrology 4/2017

Open Access 01-08-2017 | Original article

Both low and high serum ferritin levels predict mortality risk in hemodialysis patients without inflammation

Authors: Tetsuo Shoji, Kakuya Niihata, Shingo Fukuma, Shunichi Fukuhara, Tadao Akizawa, Masaaki Inaba

Published in: Clinical and Experimental Nephrology | Issue 4/2017

Login to get access

Abstract

Background

Serum ferritin concentration >100 ng/mL was associated with a higher risk of death in hemodialysis patients in Japan, whereas such an association was less clear in hemodialysis patients in Western countries. Since Japanese dialysis patients are generally less inflamed than those in Western countries, inflammation may modify the association between serum ferritin and the adverse outcomes.

Methods

We performed an observational cohort study using data from 2606 Japanese hemodialysis patients who participated in the Dialysis Outcomes and Practice Patterns Study (DOPPS) III (2005–2008) or DOPPS IV (2009–2012). The predictor was serum ferritin category (<50, 50–99.9, 100–199.9, and ≥200 ng/mL), and the primary and secondary outcomes were all-cause mortality and cardiovascular hospitalization, respectively. C-reactive protein (CRP, cut-off by 0.3 mg/dL) and serum albumin (cut-off by 3.8 g/dL) were stratification factors related to systemic inflammation.

Results

After adjustment for relevant confounding factors, a U-shaped association was observed between serum ferritin and all-cause mortality in the group with low CRP levels, whereas such relationship was not significant in the high CRP counterparts. In contrast, we found a linear association between serum ferritin and cardiovascular hospitalization in the low CRP and high CRP groups commonly. Similar results were obtained when the total cohort was stratified by serum albumin.

Conclusions

Serum ferritin showed different patterns of association with all-cause mortality in hemodialysis patients with versus without inflammation, whereas its association with cardiovascular hospitalization was similar regardless of inflammatory conditions.
Literature
1.
go back to reference Kalantar-Zadeh K, Don BR, Rodriguez RA, Humphreys MH. Serum ferritin is a marker of morbidity and mortality in hemodialysis patients. Am J Kidney Dis. 2001;37(3):564–72.CrossRefPubMed Kalantar-Zadeh K, Don BR, Rodriguez RA, Humphreys MH. Serum ferritin is a marker of morbidity and mortality in hemodialysis patients. Am J Kidney Dis. 2001;37(3):564–72.CrossRefPubMed
2.
go back to reference Kalantar-Zadeh K, Regidor DL, McAllister CJ, Michael B, Warnock DG. Time-dependent associations between iron and mortality in hemodialysis patients. J Am Soc Nephrol. 2005;16(10):3070–80.CrossRefPubMed Kalantar-Zadeh K, Regidor DL, McAllister CJ, Michael B, Warnock DG. Time-dependent associations between iron and mortality in hemodialysis patients. J Am Soc Nephrol. 2005;16(10):3070–80.CrossRefPubMed
3.
go back to reference Karaboyas A, Zee J, Morgenstern H, Nolen JG, Hakim R, Kalantar-Zadeh K, et al. Understanding the recent increase in ferritin levels in United States dialysis patients: potential impact of changes in intravenous iron and erythropoiesis-stimulating agent dosing. Clin J Am Soc Nephrol. 2015;10(10):1814–21.CrossRefPubMedPubMedCentral Karaboyas A, Zee J, Morgenstern H, Nolen JG, Hakim R, Kalantar-Zadeh K, et al. Understanding the recent increase in ferritin levels in United States dialysis patients: potential impact of changes in intravenous iron and erythropoiesis-stimulating agent dosing. Clin J Am Soc Nephrol. 2015;10(10):1814–21.CrossRefPubMedPubMedCentral
4.
go back to reference Hasuike Y, Nonoguchi H, Tokuyama M, Ohue M, Nagai T, Yahiro M, et al. Serum ferritin predicts prognosis in hemodialysis patients: the Nishinomiya study. Clin Exp Nephrol. 2010;14(4):349–55.CrossRefPubMed Hasuike Y, Nonoguchi H, Tokuyama M, Ohue M, Nagai T, Yahiro M, et al. Serum ferritin predicts prognosis in hemodialysis patients: the Nishinomiya study. Clin Exp Nephrol. 2010;14(4):349–55.CrossRefPubMed
5.
go back to reference Kuragano T, Matsumura O, Matsuda A, Hara T, Kiyomoto H, Murata T, et al. Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients. Kidney Int. 2014;86(4):845–54.CrossRefPubMed Kuragano T, Matsumura O, Matsuda A, Hara T, Kiyomoto H, Murata T, et al. Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients. Kidney Int. 2014;86(4):845–54.CrossRefPubMed
6.
go back to reference Pisoni RL, Bragg-Gresham JL, Young EW, Akizawa T, Asano Y, Locatelli F, et al. Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2004;44(1):94–111.CrossRefPubMed Pisoni RL, Bragg-Gresham JL, Young EW, Akizawa T, Asano Y, Locatelli F, et al. Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2004;44(1):94–111.CrossRefPubMed
7.
go back to reference Park KS, Ryu GW, Jhee JH, Kim HW, Park S, Lee SA, et al. Serum ferritin predicts mortality regardless of inflammatory and nutritional status in patients starting dialysis: a prospective cohort study. Blood Purif. 2015;40(3):209–17.CrossRefPubMed Park KS, Ryu GW, Jhee JH, Kim HW, Park S, Lee SA, et al. Serum ferritin predicts mortality regardless of inflammatory and nutritional status in patients starting dialysis: a prospective cohort study. Blood Purif. 2015;40(3):209–17.CrossRefPubMed
8.
go back to reference Kawaguchi T, Tong L, Robinson BM, Sen A, Fukuhara S, Kurokawa K, et al. C-reactive protein and mortality in hemodialysis patients: the dialysis outcomes and practice patterns study (DOPPS). Nephron Clin Pract. 2011;117(2):c167–78.CrossRefPubMed Kawaguchi T, Tong L, Robinson BM, Sen A, Fukuhara S, Kurokawa K, et al. C-reactive protein and mortality in hemodialysis patients: the dialysis outcomes and practice patterns study (DOPPS). Nephron Clin Pract. 2011;117(2):c167–78.CrossRefPubMed
9.
go back to reference Bazeley J, Bieber B, Li Y, Morgenstern H, de Sequera P, Combe C, et al. C-reactive protein and prediction of 1-year mortality in prevalent hemodialysis patients. Clin J Am Soc Nephrol. 2011;6(10):2452–61.CrossRefPubMedPubMedCentral Bazeley J, Bieber B, Li Y, Morgenstern H, de Sequera P, Combe C, et al. C-reactive protein and prediction of 1-year mortality in prevalent hemodialysis patients. Clin J Am Soc Nephrol. 2011;6(10):2452–61.CrossRefPubMedPubMedCentral
10.
go back to reference Young EW, Goodkin DA, Mapes DL, Port FK, Keen ML, Chen K, et al. The dialysis outcomes and practice patterns study (DOPPS): an international hemodialysisstudy. Kidney Int. 2000;57(Suppl 74):S74–81.CrossRef Young EW, Goodkin DA, Mapes DL, Port FK, Keen ML, Chen K, et al. The dialysis outcomes and practice patterns study (DOPPS): an international hemodialysisstudy. Kidney Int. 2000;57(Suppl 74):S74–81.CrossRef
11.
go back to reference Pisoni RL, Gillespie BW, Dickinson DM, Chen K, Kutner MH, Wolfe RA. The dialysis outcomes and practice patterns study (DOPPS): design, data elements, and methodology. Am J Kidney Dis. 2004;44(5 Suppl 2):7–15.CrossRefPubMed Pisoni RL, Gillespie BW, Dickinson DM, Chen K, Kutner MH, Wolfe RA. The dialysis outcomes and practice patterns study (DOPPS): design, data elements, and methodology. Am J Kidney Dis. 2004;44(5 Suppl 2):7–15.CrossRefPubMed
12.
go back to reference Tsubakihara Y, Nishi S, Akiba T, Hirakata H, Iseki K, Kubota M, et al. 2008 Japanese Society for Dialysis Therapy: guidelines for renal anemia in chronic kidney disease. Ther Apher Dial. 2010;14(3):240–75.CrossRefPubMed Tsubakihara Y, Nishi S, Akiba T, Hirakata H, Iseki K, Kubota M, et al. 2008 Japanese Society for Dialysis Therapy: guidelines for renal anemia in chronic kidney disease. Ther Apher Dial. 2010;14(3):240–75.CrossRefPubMed
13.
go back to reference KDOQI, National Kidney Foundation. KDOQI Clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis. 2006;47(5 Suppl 3):S11–145. KDOQI, National Kidney Foundation. KDOQI Clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis. 2006;47(5 Suppl 3):S11–145.
14.
go back to reference Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 2008;73(4):391–8.CrossRefPubMed Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 2008;73(4):391–8.CrossRefPubMed
15.
go back to reference Kidney Disease Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012;2(4):279–335.CrossRef Kidney Disease Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012;2(4):279–335.CrossRef
16.
go back to reference Nakai S, Masakane I, Akiba T, Iseki K, Watanabe Y, Itami N, et al. Overview of regular dialysis treatment in Japan (as of 31 December 2005). Ther Apher Dial. 2007;11(6):411–41.CrossRefPubMed Nakai S, Masakane I, Akiba T, Iseki K, Watanabe Y, Itami N, et al. Overview of regular dialysis treatment in Japan (as of 31 December 2005). Ther Apher Dial. 2007;11(6):411–41.CrossRefPubMed
17.
go back to reference Kirkali Z, Guzelsoy M, Mungan MU, Kirkali G, Yorukoglu K. Serum ferritin as a clinical marker for renal cell carcinoma: influence of tumor size and volume. Urol Int. 1999;62(1):21–5.CrossRefPubMed Kirkali Z, Guzelsoy M, Mungan MU, Kirkali G, Yorukoglu K. Serum ferritin as a clinical marker for renal cell carcinoma: influence of tumor size and volume. Urol Int. 1999;62(1):21–5.CrossRefPubMed
18.
go back to reference Kalousova M, Krechler T, Jachymova M, Kubena AA, Zak A, Zima T. Ferritin as an independent mortality predictor in patients with pancreas cancer. Results of a pilot study. Tumour Biol. 2012;33(5):1695–700.CrossRefPubMed Kalousova M, Krechler T, Jachymova M, Kubena AA, Zak A, Zima T. Ferritin as an independent mortality predictor in patients with pancreas cancer. Results of a pilot study. Tumour Biol. 2012;33(5):1695–700.CrossRefPubMed
19.
go back to reference Puntarulo S. Iron, oxidative stress and human health. Mol Asp Med. 2005;26(4–5):299–312.CrossRef Puntarulo S. Iron, oxidative stress and human health. Mol Asp Med. 2005;26(4–5):299–312.CrossRef
20.
go back to reference Nakanishi T, Hasuike Y, Otaki Y, Nanami M, Kuragano T. Dysregulated iron metabolism in patients on hemodialysis. Contrib Nephrol. 2015;185:22–31.PubMed Nakanishi T, Hasuike Y, Otaki Y, Nanami M, Kuragano T. Dysregulated iron metabolism in patients on hemodialysis. Contrib Nephrol. 2015;185:22–31.PubMed
21.
go back to reference Harada T, Baba M, Torii I, Morikawa S. Ferritin selectively suppresses delayed-type hypersensitivity responses at induction or effector phase. Cell Immunol. 1987;109(1):75–88.CrossRefPubMed Harada T, Baba M, Torii I, Morikawa S. Ferritin selectively suppresses delayed-type hypersensitivity responses at induction or effector phase. Cell Immunol. 1987;109(1):75–88.CrossRefPubMed
22.
go back to reference Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, Michaud A, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003;326(7399):1124.CrossRefPubMedPubMedCentral Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, Michaud A, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003;326(7399):1124.CrossRefPubMedPubMedCentral
23.
go back to reference Waldvogel S, Pedrazzini B, Vaucher P, Bize R, Cornuz J, Tissot JD, et al. Clinical evaluation of iron treatment efficiency among non-anemic but iron-deficient female blood donors: a randomized controlled trial. BMC Med. 2012;10:8.CrossRefPubMedPubMedCentral Waldvogel S, Pedrazzini B, Vaucher P, Bize R, Cornuz J, Tissot JD, et al. Clinical evaluation of iron treatment efficiency among non-anemic but iron-deficient female blood donors: a randomized controlled trial. BMC Med. 2012;10:8.CrossRefPubMedPubMedCentral
24.
go back to reference Kutner N, Zhang R, Johansen K, Bliwise D. Associations among nocturnal sleep, daytime intradialytic sleep, and mortality risk in patients on daytime conventional hemodialysis: US Renal Data System special study data. Hemodial Int. 2013;17(2):223–9.CrossRefPubMed Kutner N, Zhang R, Johansen K, Bliwise D. Associations among nocturnal sleep, daytime intradialytic sleep, and mortality risk in patients on daytime conventional hemodialysis: US Renal Data System special study data. Hemodial Int. 2013;17(2):223–9.CrossRefPubMed
25.
go back to reference Koyama H, Fukuda S, Shoji T, Inaba M, Tsujimoto Y, Tabata T, et al. Fatigue is a predictor for cardiovascular outcomes in patients undergoing hemodialysis. Clin J Am Soc Nephrol. 2010;5(4):659–66.CrossRefPubMedPubMedCentral Koyama H, Fukuda S, Shoji T, Inaba M, Tsujimoto Y, Tabata T, et al. Fatigue is a predictor for cardiovascular outcomes in patients undergoing hemodialysis. Clin J Am Soc Nephrol. 2010;5(4):659–66.CrossRefPubMedPubMedCentral
26.
go back to reference Dekker FW, de Mutsert R, van Dijk PC, Zoccali C, Jager KJ. Survival analysis: time-dependent effects and time-varying risk factors. Kidney Int. 2008;74(8):994–7.CrossRefPubMed Dekker FW, de Mutsert R, van Dijk PC, Zoccali C, Jager KJ. Survival analysis: time-dependent effects and time-varying risk factors. Kidney Int. 2008;74(8):994–7.CrossRefPubMed
27.
go back to reference Monda KL, Joseph PN, Neumann PJ, Bradbury BD, Rubin RJ. Comparative changes in treatment practices and clinical outcomes following implementation of a prospective payment system: the STEPPS study. BMC Nephrol. 2015;16:67.CrossRefPubMedPubMedCentral Monda KL, Joseph PN, Neumann PJ, Bradbury BD, Rubin RJ. Comparative changes in treatment practices and clinical outcomes following implementation of a prospective payment system: the STEPPS study. BMC Nephrol. 2015;16:67.CrossRefPubMedPubMedCentral
28.
go back to reference Yamamoto H, Nishi S, Tomo T, Masakane I, Saito K, Nangaku M, et al. 2015 Japanese Society for Dialysis Therapy Guideline for renal anemia in chronic kidney disease. J Jpn Soc Dial Ther. 2016;49(2):89–158 (in Japanese).CrossRef Yamamoto H, Nishi S, Tomo T, Masakane I, Saito K, Nangaku M, et al. 2015 Japanese Society for Dialysis Therapy Guideline for renal anemia in chronic kidney disease. J Jpn Soc Dial Ther. 2016;49(2):89–158 (in Japanese).CrossRef
Metadata
Title
Both low and high serum ferritin levels predict mortality risk in hemodialysis patients without inflammation
Authors
Tetsuo Shoji
Kakuya Niihata
Shingo Fukuma
Shunichi Fukuhara
Tadao Akizawa
Masaaki Inaba
Publication date
01-08-2017
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 4/2017
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-016-1317-1

Other articles of this Issue 4/2017

Clinical and Experimental Nephrology 4/2017 Go to the issue