Clinical and Experimental Nephrology

, Volume 14, Issue 1, pp 28–35 | Cite as

Maintaining high hemoglobin levels improved the left ventricular mass index and quality of life scores in pre-dialysis Japanese chronic kidney disease patients

  • Hideki HirakataEmail author
  • Yoshiharu Tsubakihara
  • Fumitake Gejyo
  • Shinichi Nishi
  • Yasuhiko Iino
  • Yuzou Watanabe
  • Masashi Suzuki
  • Akira Saito
  • Takashi Akiba
  • Daijo Inaguma
  • Shunichi Fukuhara
  • Satoshi Morita
  • Michiaki Hiroe
  • Yoshiyuki Hada
  • Makoto Suzuki
  • Makoto Akaishi
  • Kazutaka Aonuma
  • Tadao Akizawa
Original Article



Anemia is common among patients with chronic kidney disease (CKD). The introduction of erythropoietin treatment has changed anemia management, but the therapeutic hemoglobin (Hb) target is still under debate, and clinical evidence for its effect on cardiac functions and QOL is sparse.


A 16-week dose–response study and a 32-week follow-Up study were combined. After correcting anemia of less than 10 g/dl in pre-dialysis Japanese CKD patients, a higher Hb target (12–13 g/dl) by darbepoetin alfa (DPO) was compared with the conventional Hb target by epoetin alfa (EPO). Outcomes were anemia correction, management of the left ventricular mass index (LVMI) and QOL scores.


No significant difference was seen in Hb at baseline and week 16, but a significant difference was recorded at week 34 (12.34 ± 0.93 g/dl for DPO and 10.43 ± 0.90 g/dl for EPO). In both groups, LVMI decreased similarly until week 16, but the decrease of EPO was retarded, and a significant difference between LVMI was seen only in DPO at week 34 (100.7 ± 16.6 g/m2 for DPO and 110.9 ± 25.2 g/m2 for EPO). Relationships between Hb and LVMI change at week 34 were examined by stratifying Hb into four groups (Hb <10 g/dl, 10 g/dl ≤ Hb <11 g/dl, 11 g/dl ≤ Hb <12 g/dl and 12 g/dl ≤ Hb), and a decrease of LVMI was prominent in the 12 g/dl ≤ Hb group. Correction of anemia to 11 g/dl or more led to improved QOL scores. No safety difference was observed among the treatments.


Targeting a higher Hb around 12 g/dl was more beneficial than targeting conventional Hb in terms of reduction of LVMI and QOL. Further studies to determine the appropriate Hb target are necessary.


Anemia Cardiac functions Chronic kidney disease Erythropoietin Quality of life 



The dose–response and follow-up studies were sponsored by Kirin Pharma Company, Ltd.


  1. 1.
    Vella JP, O’Neill D, Atkins N, Donohoe JF, Walshe JJ. Sensitization to human leukocyte antigen before and after the introduction of erythropoietin. Nephrol Dial Transpl. 1998;13:2027–32.CrossRefGoogle Scholar
  2. 2.
    National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease in adults. Am J Kidney Dis. 2006;47 Suppl 3:S16–85.Google Scholar
  3. 3.
    Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355:2085–98.CrossRefPubMedGoogle Scholar
  4. 4.
    Roger SD, Levin A. Epoetin trials: randomized controlled trials don’t always mimic observational data. Nephrol Dial Transpl. 2007;22:684–6.CrossRefGoogle Scholar
  5. 5.
    Strippoli GFM, Tognoni G, Navaneethan SD, Nicolucci A, Craig JC. Haemoglobin targets: we were wrong, time to move on. Lancet. 2007;369:346–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Li S, Collins AJ. Association of hematocrit value with cardiovascular morbidity and mortality in incident hemodialysis patients. Kidney Int. 2004;65:626–33.CrossRefPubMedGoogle Scholar
  7. 7.
    Pisoni RL, Bragg-Gresham JL, Young EW, et al. Anemia management and outcomes from 12 countries in the dialysis outcomes and practice patterns study (DOPPS). Am J Kidney Dis. 2004;44:94–111.CrossRefPubMedGoogle Scholar
  8. 8.
    Amaral S, Hwang W, Fivush B, et al. Association of mortality and hospitalization with achievement of adult hemoglobin targets in adolescents maintained on hemodialysis. J Am Soc Nephrol. 2006;17:2878–85.CrossRefPubMedGoogle Scholar
  9. 9.
    Regidor DL, Kopple JD, Kovesdy CP, et al. Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients. J Am Soc Nephrol. 2006;17:1181–91.CrossRefPubMedGoogle Scholar
  10. 10.
    Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355:2071–84.CrossRefPubMedGoogle Scholar
  11. 11.
    Fukuhara S, Yamazaki S, Marumo F, et al. Health-related quality of life of predialysis patients with chronic renal failure. Nephron Clin Pract. 2007;105:c1–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Locatelli F, Aljama P, Barany P, et al.: Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transpl. 2004;19 Suppl 2:ii1–47.Google Scholar
  13. 13.
    Hayashi T, Suzuki A, Shoji T, et al. Cardiovascular effect of normalizing the hematocrit level during erythropoietin therapy in predialysis patients with chronic renal failure. Am J Kidney Dis. 2000;35:250–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Macdougall IC, Matcham J, Gray SJ, et al. Correction of anaemia with darbepoetin alfa in patients with chronic kidney disease receiving dialysis. Nephrol Dial Transpl. 2003;18:576–81.CrossRefGoogle Scholar
  15. 15.
    Parfrey PS, Foley RN, Wittreich BH, et al. Double-blind comparison of full and partial anemia correction in incident hemodialysis patients without symptomatic heart disease. J Am Soc Nephrol. 2005;16:2180–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Rossert J, Levin A, Roger SD, et al. Effect of early correction of anemia on the progression of CKD. Am J Kidney Dis. 2006;47:738–50.CrossRefPubMedGoogle Scholar
  17. 17.
    Mac dougall IC, Gray SJ, Elston O, et al. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. J Am Soc Nephrol. 1999;10(11):2392–5.Google Scholar
  18. 18.
    Vanrenterghem Y, Barany P, Mann JFE, et al. Randomized trial of darbepoetin alfa for treatment of renal anemia at a reduced dose frequency compared with rHuEPO in dialysis patients. Kidney Int. 2002;62:2167–75.CrossRefPubMedGoogle Scholar
  19. 19.
    Locatelli F, Pisoni RL, Combe C, et al. Anaemia in haemodialysis patients of five European countries: association with morbidity and mortality in the dialysis outcomes and practice patterns study (DOPPS). Nephrol Dial Transpl. 2004;19:121–32.CrossRefGoogle Scholar
  20. 20.
    Silverberg DS, Wexler D, Blum M, et al. The effect of correction of anaemia in diabetics and non-diabetics with severe resistant congestive heart failure and chronic renal failure by subcutaneous erythropoietin and intravenous iron. Nephrol Dial Transpl. 2003;18:141–6.CrossRefGoogle Scholar
  21. 21.
    Ritz E, Laville M, Bilous RW, et al. Target level for hemoglobin correction in patients with diabetes and CKD: primary results of the anemia correction in diabetes (ACORD) Study. Am J Kidney Dis. 2007;49:194–207.CrossRefPubMedGoogle Scholar
  22. 22.
    National Kidney Foundation. KDOQI clinical practice guideline and clinical practice recommendations for anemia in chronic kidney disease: update of hemoglobin target. Am J Kidney Dis. 2007;50:471–530.CrossRefGoogle Scholar
  23. 23.
    Mix TC, Brenner RM, Cooper ME, et al. Trial to reduce cardiovascular events with aranesp therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease. Am Heart J. 2005;149:408–13.CrossRefPubMedGoogle Scholar
  24. 24.
    Pfeffer MA, for the TREAT executive committee. An Ongoing Study of Anemia Correction in Chronic Kidney Disease. N Engl J Med. 2007;356:959–61.Google Scholar
  25. 25.
    Szczech L, Barnhart H, Inrig J, et al. Secondary analysis of the CHOIR trial epoetin-alfa dose and achieved hemoglobin outcomes. Kidney Int. 2008. doi: 10.1038/ki.2008.295.

Copyright information

© Japanese Society of Nephrology 2009

Authors and Affiliations

  • Hideki Hirakata
    • 1
    Email author
  • Yoshiharu Tsubakihara
    • 2
  • Fumitake Gejyo
    • 3
  • Shinichi Nishi
    • 3
  • Yasuhiko Iino
    • 4
  • Yuzou Watanabe
    • 5
  • Masashi Suzuki
    • 6
  • Akira Saito
    • 7
  • Takashi Akiba
    • 8
  • Daijo Inaguma
    • 9
  • Shunichi Fukuhara
    • 10
  • Satoshi Morita
    • 11
  • Michiaki Hiroe
    • 12
  • Yoshiyuki Hada
    • 13
  • Makoto Suzuki
    • 14
  • Makoto Akaishi
    • 15
  • Kazutaka Aonuma
    • 16
  • Tadao Akizawa
    • 17
  1. 1.Fukuoka Red Cross HospitalFukuokaJapan
  2. 2.Osaka General Medical CenterOsakaJapan
  3. 3.Niigata University Medical and Dental HospitalNiigataJapan
  4. 4.Nippon Medical University HospitalTokyoJapan
  5. 5.Kasugai Municipal HospitalKasugaiJapan
  6. 6.Shinrakuen HospitalNiigataJapan
  7. 7.Tokai University HospitalTokyoJapan
  8. 8.Tokyo Women’s Medical UniversityTokyoJapan
  9. 9.Tosei General HospitalAichiJapan
  10. 10.Kyoto University Graduate School of MedicineKyotoJapan
  11. 11.Yokohama City University General Medical CenterYokohamaJapan
  12. 12.International Medical Center of JapanTokyoJapan
  13. 13.Sakakibara Memorial ClinicTokyoJapan
  14. 14.Ohashi Medical CenterToho UniversityTokyoJapan
  15. 15.Kitasato Institute HospitalKitasato UniversityTokyoJapan
  16. 16.Tsukuba University HospitalTsukubaJapan
  17. 17.Showa University School of MedicineTokyoJapan

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