Skip to main content

Advertisement

SpringerLink
Log in

Mean corpuscular hemoglobin concentration: an anemia parameter predicting cardiovascular disease in incident dialysis patients

  • Original Article
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Background

Hemoglobin levels usually decline before dialysis initiation. The influence of overhydration on anemia progression and iron sequestration is poorly documented. Furthermore, clinical implications of anemia at dialysis initiation remain to be elucidated.

Methods

This multicenter retrospective cohort study enrolled incident dialysis patients. The patients were stratified by tertiles of overhydration rate (OH-R) defined by (BW − DW)/DW*100 (BW: body weight just before dialysis initiation, DW: dry weight). Time courses (6 months before, to 1 month after, dialysis initiation) of hemoglobin, C-reactive protein (CRP), and iron sequestration index (ISI) were examined using mixed effects models. We used Cox models to identify anemia parameters predicting subsequent cardiovascular disease (CVD).

Results

Among the 905 enrolled patients, hemoglobin levels gradually decreased before dialysis initiation and rapidly increased thereafter. An inverse V-shaped time course was observed for CRP and ISI with an increase during dialysis initiation. Patients with a higher OH-R showed lower hemoglobin levels along with higher CRP and ISI levels before dialysis initiation. Mean corpuscular hemoglobin concentration (MCHC) was more stable before dialysis initiation than were mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Low MCHC (< 32 g/dL) was independently associated with the incidence of nonatherosclerotic CVD. Patients with low MCHC tended to have increased left ventricular wall thickness and left atrial diameter.

Conclusions

Progression of anemia before dialysis among overhydrated patients may mainly occur through hemodilution and iron sequestration partly induced by inflammation. Low MCHC reflects left atrial overload and left ventricular hypertrophy and hence may predict nonatherosclerotic CVD.

Graphic abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kawamoto S, Kaneko Y, Misawa H et al (2018) Lower Hb at the initiation of dialysis does not adversely affect 1-year mortality rate. Ren Replace Ther 4:4

    Article  Google Scholar 

  2. Kataoka H, Tsuchiya K, Naganuma T et al (2015) Relation between anaemia management at haemodialysis initiation and patient prognosis. Nephrology (Carlton) 20(Suppl 4):14–21

    Article  CAS  Google Scholar 

  3. Nangaku M, Mimura I, Yamaguchi J, Higashijima Y, Wada T, Tanaka T (2015) Role of uremic toxins in erythropoiesis-stimulating agent resistance in chronic kidney disease and dialysis patients. J Ren Nutr 25:160–163

    Article  CAS  Google Scholar 

  4. Hung SC, Kuo KL, Peng CH, Wu CH, Wang YC, Tarng DC (2015) Association of fluid retention with anemia and clinical outcomes among patients with chronic kidney disease. J Am Heart Assoc 4:e001480

    PubMed  PubMed Central  Google Scholar 

  5. Yilmaz Z, Yildirim Y, Oto F et al (2014) Evaluation of volume overload by bioelectrical impedance analysis, NT-proBNP and inferior vena cava diameter in patients with stage 3 & 4 and 5 chronic kidney disease. Ren Fail 36:495–501

    Article  Google Scholar 

  6. Wheeler D, London GM, Parfrey PS et al (2014) Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the evaluation of cinacalcet HCI therapy to lower cardiovascular events (EVOLVE) trail. J Am Heart Assoc 3:e001363

    Article  Google Scholar 

  7. Stancu SH, Stanciu A, Lipan M, Capusa C (2018) Renal anemia and hydration status in non-dialysis chronic kidney disease: is there a link? J Med Life 11:293–298

    Google Scholar 

  8. Testani JM, Chen J, McCauley BD, Kimmel SE, Shannon RP (2010) Potential effects of aggressive decongestion during the treatment of decompensated heart failure on renal function and survival. Circulation 122:265–272

    Article  Google Scholar 

  9. Davila C, Reyentovich A, Katz SD (2011) Clinical correlates of hemoconcentration during hospitalization for acute decompensated heart failure. J Card Fail 17:1018–1022

    Article  Google Scholar 

  10. Gonçalves S, Pecoits-Filho R, Perreto S et al (2006) Associations between renal function, volume status and endotoxaemia in chronic kidney disease patients. Nephrol Dial Transplant 21:2788–2794

    Article  Google Scholar 

  11. Yilmaz MI, Solak Y, Covic A, Goldsmith D, Kanbay M (2011) Renal anemia of inflammation: the name is self-explanatory. Blood Purif 32:220–225

    Article  Google Scholar 

  12. Tsai YC, Chiu YW, Tsai JC, Kuo HT, Hung CC, Hwang SJ et al (2015) Association of fluid overload with cardiovascular morbidity and all-cause mortality in stage 4 and 5 CKD. Clin J Am Soc Nephrol 10:39–46

    Article  CAS  Google Scholar 

  13. Kalantar-Zadeh K, Regidor DL, Kovesdy CP et al (2009) Fluid retention is associated with cardiovascular mortality in patients undergoing long-term hemodialysis. Circulation 119:671–679

    Article  Google Scholar 

  14. Onofriescu M, Siriopol D, Voroneanu L et al (2015) Overhydration, cardiac function and survival in hemodialysis patients. PLoS ONE 10:e0135691

    Article  Google Scholar 

  15. Koo HM, Kim CH, Doh FM et al (2014) The relationship of initial transferrin saturation to cardiovascular parameters and outcomes in patients initiating dialysis. PLoS ONE 9:e87231

    Article  Google Scholar 

  16. Cuevas X, Carcía F, Martín-Malo A et al (2012) Risk factors associated with cardiovascular morbidity and mortality in Spanish incident hemodialysis patients: 2-year results from the ANSWER study. Blood Purif 33:21–29

    Article  Google Scholar 

  17. Okonko DO, Mandal AKJ, Missouris CG, Poole-Wilson PA (2011) Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. J Am Coll Cardiol 58:1241–1251

    Article  CAS  Google Scholar 

  18. Maeder MT, Khammy O, dos Remedios C, Kaye DM (2011) Myocardial and systemic iron depletion in heart failure implications for anemia accompanying heart failure. J Am Coll Cardiol 58:474–480

    Article  CAS  Google Scholar 

  19. Haddad S, Wang Y, Galy B et al (2017) Iron-regulatory proteins secure iron availability in cardiomyocytes to prevent heart failure. Eur Heart J 38:362–372

    CAS  PubMed  Google Scholar 

  20. Melenovsky V, Petrak J, Mracek T et al (2017) Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis. Eur J Heart Fail 19:522–530

    Article  CAS  Google Scholar 

  21. Hammadah M, Brennan ML, Wu Y, Hazen SL et al (2016) Usefulness of relative hypochromia in risk stratification for nonanemic patients with chronic heart failure. Am J Cardiol 117:1299–1304

    Article  Google Scholar 

  22. Hameed SM, Aird WC, Cohn SM (2003) Oxygen delivery. Crit Care Med 31:S658-667

    Article  CAS  Google Scholar 

  23. Hansen ES, Gellett S, Kirkegård L, Hjortdal V, Gottrup F (1989) Tissue oxygen tension in random pattern skin flaps during normovolemic hemodilution. J Surg Res 47:24–29

    Article  CAS  Google Scholar 

  24. Mason DT, Awan NA, Joye JA, Lee G, DeMaria AN, Amsterdam EA (1980) Treatment of acute and chronic congestive heart failure by vasodilator-afterload reduction. Arch Intern Med 140:1577–1581

    Article  CAS  Google Scholar 

  25. Kannel WB (1987) Epidemiology and prevention of cardiac failure: Framingham Study insights. Eur Heart J 8:23–26

    Article  Google Scholar 

  26. Simbaqueba C, Shrestha K, Patarroyo M et al (2013) Prognostic implications of relative hypochromia in ambulatory patients with chronic systolic heart failure. Congest Heart Fail 19:180–185

    Article  Google Scholar 

  27. Kleber M, Kozhuharov N, Sabti Z, Glatz B, Isenreich R, Wussler D et al (2019) Relative hypochromia and mortality in acute heart failure. Int J Cardiol 286:104–110

    Article  Google Scholar 

  28. Ebrahimi V, Khademian MH, Masoumi SJ, Morvaridi MR, Ezzatzadegan JS (2019) Factors influencing survival time of hemodialysis patients; time to event analysis using parametric models: a cohort study. BMC Nephrol 20:215

    Article  Google Scholar 

  29. Aslinia F, Mazza JJ, Yale SH (2006) Megaloblastic anemia and other causes of macrocytosis. Clin Med Res 4:236–241

    Article  Google Scholar 

  30. Hsieh YP, Chang CC, Kor CT, Yang Y, Wen YK, Chiu PF (2017) Mean corpuscular volume and mortality in patients with CKD. Clin J Am Soc Nephrol 12:237–244

    Article  CAS  Google Scholar 

  31. Tennankore KK, Soroka SD, West KA, Kiberd BA (2011) Macrocytosis may be associated with mortality in chronic hemodialysis patients: a prospective study. BMC Nephrol 12:19

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr. Shihomi Maeda, Dr. Fumiyuki Morioka, Dr. Syou Matsui, Dr. Sayaka Katou, Dr. Akane Ito, Dr. Eriko Iwahashi, (JCHO Osaka Hospital), Dr. Kiyoshi Shozu (Aino Hospital), Dr. Yutaro Azuma (Azuma Dialysis Clinic), Dr. Akira Wada (Azuma Renal Clinic), Dr. Jong Il Kim (Chibune Kidney and Dialysis Clinic), Dr. Sachiko Yamada (Saiseikai Ibaraki Hospital), Dr. Yasuhiro Enomoto (Enomoto Clinic), Dr. Ryoichi Miyazaki (Fujita Memorial Hospital), Dr. Yuji Murata (Harbor-Town Clinic), Dr. Toshiaki Hirabayashi (Heimeikai Clinic), Dr. Isao Fukuhara (Heisei Urologic Clinic), Dr. Shigeru Yamaguchi (Hokusetsu General Hospital), Dr. Takashi Tomokuni (Ibaraki Iseikai Hospital), Dr. Toyohumi Fukuda (Ibuki Clinic), Dr. Kazuyuki Hayashi (Ikeda Municipal Hospital), Dr. Nobuyuki Imai (Imai Naika Clinic), Dr. Yasuji Kuroda (Inadera Dialysis Clinic), Dr. Yuko Fujiwara, Dr. Yoshihiro Tsujimoto (Inoue Hospital), Dr. Takahisa Hotta (Iseikai Fuzoku Clinic), Dr. Takahiro Fujii (Itami Bara Clinic), Dr. Tomoko Yokokawa (Itami Gardens Clinic), Dr. Kazuo Yasuda (Jinyuukai Yasuda Clinic), Dr. Masanori Joko (Joko Clinic), Dr. Yukiomi Namba (Jouto Iseikai Clinic), Dr. Jyunya Takahara (Takahara Clinic), Dr. Mayumi Sakurai (Jyurakukai Clinic), Dr. Masato Baden (Kaiseikai Takarazuka Hospital), Dr. Hisato Nakamori (Katano Hospital), Dr. Hironori Kawamura (Kawamura Clinic), Dr. Chikako Monden (Kisei Hospital), Dr. Ken Kishida (Kishida Clinic), Dr. Eikun Maruyama (Kitagawa Clinic), Dr. Fumi Sato (KKR Otemae Hospital), Dr. Shigeru Hanada (Koseikai Taisei Clinic), Dr. Akihisa Kuki (Kuki Clinic), Dr. Takayuki Okamoto (Kyoritsu Hospital), Dr. Mitsuru Kubo (Kyowakai Hospital), Dr. Haruki Fuse (Maizuru Kyosai Hospital), Dr. Yutaka Matsui (Matsui Dietary & Dementia Clinic), Dr. Noriko Mikami (Mikami Clinic), Dr. Hiroshi Miyao (Miyo Urology Clinic), Dr. Mutsuko Mori (Mori Clinic), Dr. Rumi Sakai (Motoyama Sakai Rumi Clinic), Dr. Shunro Agata (Nagahara Hospital), Dr. Takanori Nagai (Nagai Clinic), Dr. Hideyuki Nakagawa (Nakagawa Clinic), Dr. Masashi Shinozaki (Nakano Clinic), Dr. Yasuo Ohyama (Neyagawa Keijinkai Clinic), Dr. Kanji Nozaki (Nozaki Clinic), Dr. Tetsuya Kaneko (NTT West Osaka Hospital), Dr. Takeshi Omichi (Ohmichi Clinic), Dr. Motohiro Okamura (Okamuraiin Jin Clinic), Dr. Akira Okasho (Okasho Urology Clinic), Dr. Kiyoshi Goto (Ono-Naika Clinic), Dr. Hidekazu Shimizu (Onoyama Clinic), Dr. Masahiro Kyo (Osaka Umeda Iseikai Dialysis Clinic), Dr. Nobuhiko Narukawa (Sakuragaoka Hospital), Dr. Kei Hirai (Sanko Clinic), Dr. Kazuhisa Yamamoto (Sanko hospital), Dr. Satoshi Sasaki (Sasaki Medical Clinic), Dr. Masugi Satoh (Satoh Clinic Kuzuha), Dr. Daisuke Nakagawa (Second Rokushima Clinic), Dr. Hiroyuki Araki (Settsu Iseikai Hospital), Dr. Shintaro Yamanaka (Shingu Municipal Medical Center), Dr. Atsushi Yokota (Shin-Osaka Iseikai Clinic), Dr. Ken Takahara (Sone Hospital), Dr. Zenzo Fujii (St. Hill Hospital), Dr. Jun Matsuda (Suita City Hospital), Dr. Yoshinori Sai (Suminodo Clinic), Dr. Kanji Yoshida (Suzawa Clinic), Dr. Tadashi Hatayama (Neyagawaikunobyouinn), Dr. Yukito Kokado, Dr. Tohru Takahashi (Takahashi Clinic), Dr. Kazuyuki Takahashi (Takahashi Kazuyuki Clinic), Dr. Yoshiaki Hirosue (Takasago Municipal Hospital), Dr. K.Y. (Tanaka Clinic), Dr. Masatou Tanaka (Tanaka Urology Clinic Dialysis Center Furuedai), Dr. Hiroko Tokizane (Tokizane Clinic), Dr. Keiji Isshiki (Tomita Clinic), Dr. Jun Tomita (Toyonaka Watanabe Clinic, Kansai Medical Hospital), Dr. Yumiko Honda (Toyonakamidorigaoka Hospital), Dr. Takahide Sugiyama (Tsukuno Fujii Clinic), Dr. Akira Moriguchi (Umeda-Higashi Blood Purification Clinic), Dr. Takatoshi Yamamoto (Yamamoto Clinic), Dr. Masaru Shin (Yao Tokushukai General Hospital), and Dr. Toru Yoshie (Yoshie Hospital) for their assistance in collecting data.

Funding

This study was supported by Osaka Heart Club. Funders had no role in analysis and interpretation of the data or approval of the manuscript.

Author information

Authors and Affiliations

  1. Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Satoshi Yamaguchi, Takayuki Hamano, Tatsufumi Oka, Yohei Doi, Sachio Kajimoto, Karin Shimada, Ayumi Matsumoto, Isao Matsui & Yoshitaka Isaka

  2. Department of Internal Medicine, Japan Community Health care Organization Osaka Hospital, Osaka, Japan

    Satoshi Yamaguchi & Akira Suzuki

  3. Department of Nephrology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8602, Japan

    Takayuki Hamano

  4. Department of Inter-Organ Communication Research in Kidney Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Yusuke Sakaguchi

Authors
  1. Satoshi Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takayuki Hamano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tatsufumi Oka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yohei Doi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sachio Kajimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Karin Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ayumi Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yusuke Sakaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Isao Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Akira Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yoshitaka Isaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SY, TH, YD, TO, YS, AS, and YI contributed to the study design. All authors were involved in data acquisition and interpretation of the results. Data analysis was done by SY. Supervision was done by TH and YI. SY and TH drafted the report, and the other authors gave critical revision of the manuscript for scientific and factual content.

Corresponding author

Correspondence to Takayuki Hamano.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

We enrolled patients with CKD stage 5 who started hemodialysis from January 2008 to December 2016 at Osaka University Hospital or from January 2007 to July 2018 at the Japan Community Health care Organization (JCHO) Osaka Hospital. We excluded patients aged < 20 years and those who started dialysis at the intensive care unit of Osaka University Hospital. This study was approved by the Osaka University Hospital Ethics Committee (No. 18026) and was performed according to the tenets of the Helsinki Declaration.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamaguchi, S., Hamano, T., Oka, T. et al. Mean corpuscular hemoglobin concentration: an anemia parameter predicting cardiovascular disease in incident dialysis patients. J Nephrol 35, 535–544 (2022). https://doi.org/10.1007/s40620-021-01107-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-021-01107-w

Keywords

Search

Navigation