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Published in: Clinical and Experimental Nephrology 4/2016

01-08-2016 | Original Article

Impact of hemoglobin levels on renal and non-renal clinical outcomes differs by chronic kidney disease stages: the Gonryo study

Authors: Tae Yamamoto, Mariko Miyazaki, Masaaki Nakayama, Gen Yamada, Masato Matsushima, Mistuhiro Sato, Toshinobu Sato, Yoshio Taguma, Hiroshi Sato, Sadayoshi Ito

Published in: Clinical and Experimental Nephrology | Issue 4/2016

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Abstract

Background

Anemia greatly affects the development of renal and cardiovascular outcomes in chronic kidney disease (CKD) patients. However, the impact based on CKD stage remains unclear.

Methods

We prospectively followed 2,602 Japanese CKD patients under the care of nephrologists. CKD was defined according to cause, estimated glomerular filtration rate <60 mL/min, and/or proteinuria. Patient outcomes [primary end-points: cardiovascular events (CVEs), all-cause mortality, and end-stage kidney disease (ESKD) requiring renal replacement therapy] were assessed in association with basal hemoglobin (Hb) levels (<10, 10–12 and ≥12 g/dL), stratified by CKD stages.

Results

During follow-up, 123 patients developed CVEs, 41 died, and 220 progressed to ESKD. For stages G3, G4 and G5, ESKD frequencies were 2.8, 64.4, and 544.8 person-years, while CVEs and death were 25.6, 45.6, and 76.3 person-years, respectively. The combined endpoint rate was significantly higher in patients with Hb <10 versus Hb 10–12 g/dL, but a higher risk for CVEs and death with Hb <10 g/dL was found only in G3 [hazard ratio (HR) 4.49, (95 % confidence interval (95 % CI) 2.06–9.80)]. In contrast, risk for ESKD with Hb <10 g/dL was found only in G4 [HR 3.08 (95 % CI 1.40–6.79)] and G5 [HR 1.43 (95 % CI 1.01–2.05)]. No increased risks with higher Hb levels were found.

Conclusion

The impact of renal anemia of Hb <10 g/dL on clinical outcomes differed by CKD stage, with a significantly high risk for CVEs and all-cause mortality in G3 and progression to ESKD in G4 and G5.
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Literature
1.
go back to reference Go AS, Yang J, Ackerson LM, Lepper K, Robbins S, Massie BM, et al. Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. Circulation. 2006;113:2713–23.CrossRefPubMed Go AS, Yang J, Ackerson LM, Lepper K, Robbins S, Massie BM, et al. Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. Circulation. 2006;113:2713–23.CrossRefPubMed
2.
go back to reference Silverberg DS, Wexler D, Blum M, Tchebiner JZ, Sheps D, Keren G, 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 Transplant. 2003;18:141–6.CrossRefPubMed Silverberg DS, Wexler D, Blum M, Tchebiner JZ, Sheps D, Keren G, 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 Transplant. 2003;18:141–6.CrossRefPubMed
3.
go back to reference Tseng CL, Kern EF, Miller DR, Tiwari A, Maney M, Rajan M, et al. Survival benefit of nephrologic care in patients with diabetes mellitus and chronic kidney disease. Arch Intern Med. 2008;168:55–62.CrossRefPubMed Tseng CL, Kern EF, Miller DR, Tiwari A, Maney M, Rajan M, et al. Survival benefit of nephrologic care in patients with diabetes mellitus and chronic kidney disease. Arch Intern Med. 2008;168:55–62.CrossRefPubMed
4.
go back to reference De Nicola L, Minutolo R, Chiodini P, Zamboli P, Cianciaruso B, Nappi F, et al. Prevalence and prognosis of mild anemia in non-dialysis chronic kidney disease: a prospective cohort study in outpatient renal clinics. Am J Nephrol. 2010;32:533–40.CrossRefPubMed De Nicola L, Minutolo R, Chiodini P, Zamboli P, Cianciaruso B, Nappi F, et al. Prevalence and prognosis of mild anemia in non-dialysis chronic kidney disease: a prospective cohort study in outpatient renal clinics. Am J Nephrol. 2010;32:533–40.CrossRefPubMed
5.
go back to reference De Nicola L, Chiodini P, Zoccali C, Borrelli S, Cianciaruso B, Di Iorio B, et al. Prognosis of CKD patients receiving outpatient nephrology care in Italy. Clin J Am Soc Nephrol. 2011;6:2421–8.CrossRefPubMedPubMedCentral De Nicola L, Chiodini P, Zoccali C, Borrelli S, Cianciaruso B, Di Iorio B, et al. Prognosis of CKD patients receiving outpatient nephrology care in Italy. Clin J Am Soc Nephrol. 2011;6:2421–8.CrossRefPubMedPubMedCentral
6.
go back to reference Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355:2071–84.CrossRefPubMed Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355:2071–84.CrossRefPubMed
7.
go back to reference Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355:2085–98.CrossRefPubMed Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355:2085–98.CrossRefPubMed
8.
go back to reference Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361:2019–32.CrossRefPubMed Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361:2019–32.CrossRefPubMed
9.
go back to reference KDIGO Clinical Practice Guideline for Anemia in Chronic. Kidney disease. Kidney Int Suppl. 2012;2:279–335.CrossRef KDIGO Clinical Practice Guideline for Anemia in Chronic. Kidney disease. Kidney Int Suppl. 2012;2:279–335.CrossRef
10.
go back to reference Japanese Society of Nephrology. Evidence-based practice guideline for the treatment of CKD. Clin Exp Nephrol. 2009;13:537–66.CrossRef Japanese Society of Nephrology. Evidence-based practice guideline for the treatment of CKD. Clin Exp Nephrol. 2009;13:537–66.CrossRef
11.
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;14:240–75.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;14:240–75.CrossRefPubMed
12.
go back to reference Kuriyama S, Tomonari H, Yoshida H, Hashimoto T, Kawaguchi Y, Sakai O. Reversal of anemia by erythropoietin therapy retards the progression of chronic renal failure, especially in nondiabetic patients. Nephron. 1997;77:176–85.CrossRefPubMed Kuriyama S, Tomonari H, Yoshida H, Hashimoto T, Kawaguchi Y, Sakai O. Reversal of anemia by erythropoietin therapy retards the progression of chronic renal failure, especially in nondiabetic patients. Nephron. 1997;77:176–85.CrossRefPubMed
13.
go back to reference Tsubakihara Y, Gejyo F, Nishi S, Iino Y, Watanabe Y, Suzuki M, et al. High target hemoglobin with erythropoiesis-stimulating agents has advantages in the renal function of non-dialysis chronic kidney disease patients. Ther Apher Dial. 2012;16:529–40.CrossRefPubMed Tsubakihara Y, Gejyo F, Nishi S, Iino Y, Watanabe Y, Suzuki M, et al. High target hemoglobin with erythropoiesis-stimulating agents has advantages in the renal function of non-dialysis chronic kidney disease patients. Ther Apher Dial. 2012;16:529–40.CrossRefPubMed
14.
go back to reference Akizawa T, Gejyo F, Nishi S, Iino Y, Watanabe Y, Suzuki M, et al. Positive outcomes of high hemoglobin target in patients with chronic kidney disease not on dialysis: a randomized controlled study. Ther Apher Dial. 2011;15:431–40.CrossRefPubMed Akizawa T, Gejyo F, Nishi S, Iino Y, Watanabe Y, Suzuki M, et al. Positive outcomes of high hemoglobin target in patients with chronic kidney disease not on dialysis: a randomized controlled study. Ther Apher Dial. 2011;15:431–40.CrossRefPubMed
15.
go back to reference Akaishi M, Hiroe M, Hada Y, Suzuki M, Tsubakihara Y, Akizawa T, KRN321 Study Group. Effect of anemia correction on left ventricular hypertrophy in patients with modestly high hemoglobin level and chronic kidney disease. J Cardiol. 2013;62:249–56.CrossRefPubMed Akaishi M, Hiroe M, Hada Y, Suzuki M, Tsubakihara Y, Akizawa T, KRN321 Study Group. Effect of anemia correction on left ventricular hypertrophy in patients with modestly high hemoglobin level and chronic kidney disease. J Cardiol. 2013;62:249–56.CrossRefPubMed
16.
go back to reference Iseki K, Ikemiya Y, Iseki C, Takishita S. Haematocrit and the risk of developing end-stage renal disease. Nephrol Dial Transplant. 2003;18:899–905.CrossRefPubMed Iseki K, Ikemiya Y, Iseki C, Takishita S. Haematocrit and the risk of developing end-stage renal disease. Nephrol Dial Transplant. 2003;18:899–905.CrossRefPubMed
17.
go back to reference Mohanram A, Zhang Z, Shahinfar S, Keane WF, Brenner BM, Toto RD. Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy. Kidney Int. 2004;66:1131–8.CrossRefPubMed Mohanram A, Zhang Z, Shahinfar S, Keane WF, Brenner BM, Toto RD. Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy. Kidney Int. 2004;66:1131–8.CrossRefPubMed
18.
go back to reference Nakayama M, Sato T, Sato H, Yamaguchi Y, Obara K, Kurihara I. Different clinical outcomes for cardiovascular events and mortality in chronic kidney disease according to underlying renal disease: the Gonryo study. Clin Exp Nephrol. 2010;14:333–9.CrossRefPubMed Nakayama M, Sato T, Sato H, Yamaguchi Y, Obara K, Kurihara I. Different clinical outcomes for cardiovascular events and mortality in chronic kidney disease according to underlying renal disease: the Gonryo study. Clin Exp Nephrol. 2010;14:333–9.CrossRefPubMed
19.
go back to reference Nakayama M, Sato T, Miyazaki M, Matsushima M, Sato H, Taguma Y, et al. Increased risk of cardiovascular events and mortality among non-diabetic chronic kidney disease patients with hypertensive nephropathy: the Gonryo study. Hypertens Res. 2011;34:1106–10.CrossRefPubMed Nakayama M, Sato T, Miyazaki M, Matsushima M, Sato H, Taguma Y, et al. Increased risk of cardiovascular events and mortality among non-diabetic chronic kidney disease patients with hypertensive nephropathy: the Gonryo study. Hypertens Res. 2011;34:1106–10.CrossRefPubMed
20.
go back to reference Special report from the National Institute of Neurological. Disorders and Stroke. Classification of cerebrovascular diseases III. Stroke. 1990;21:637–76.CrossRef Special report from the National Institute of Neurological. Disorders and Stroke. Classification of cerebrovascular diseases III. Stroke. 1990;21:637–76.CrossRef
21.
go back to reference Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefPubMed Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefPubMed
22.
go back to reference Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706.CrossRefPubMed Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706.CrossRefPubMed
23.
go back to reference Akizawa T, Saito A, Gejyo F, Suzuki M, Nishizawa Y, Tomino Y, et al. Impacts of recombinant human erythropoietin treatment during predialysis periods on the progression of chronic kidney disease in a large-scale cohort study (Co-JET study). Ther Apher Dial. 2014;18:140–8.CrossRefPubMed Akizawa T, Saito A, Gejyo F, Suzuki M, Nishizawa Y, Tomino Y, et al. Impacts of recombinant human erythropoietin treatment during predialysis periods on the progression of chronic kidney disease in a large-scale cohort study (Co-JET study). Ther Apher Dial. 2014;18:140–8.CrossRefPubMed
24.
go back to reference Gouva C, Nikolopoulos P, Ioannidis JP, Siamopoulos KC. Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kidney Int. 2004;66:753–60.CrossRefPubMed Gouva C, Nikolopoulos P, Ioannidis JP, Siamopoulos KC. Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kidney Int. 2004;66:753–60.CrossRefPubMed
25.
go back to reference Solomon SD, Uno H, Lewis EF, Eckardt KU, Lin J, Burdmann EA, et al. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med. 2010;363:1146–55.CrossRefPubMed Solomon SD, Uno H, Lewis EF, Eckardt KU, Lin J, Burdmann EA, et al. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med. 2010;363:1146–55.CrossRefPubMed
26.
go back to reference Skali H, Lin J, Pfeffer MA, Chen CY, Cooper ME, McMurray JJ, et al. Hemoglobin stability in patients with anemia, CKD, and type 2 diabetes: an analysis of the TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) placebo arm. Am J Kidney Dis. 2013;61:238–46.CrossRefPubMed Skali H, Lin J, Pfeffer MA, Chen CY, Cooper ME, McMurray JJ, et al. Hemoglobin stability in patients with anemia, CKD, and type 2 diabetes: an analysis of the TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) placebo arm. Am J Kidney Dis. 2013;61:238–46.CrossRefPubMed
27.
go back to reference Akizawa T, Makino H, Matsuo S, Watanabe T, Imai E, Nitta K, et al. Management of anemia in chronic kidney disease patients: baseline findings from Chronic Kidney Disease Japan Cohort Study. Clin Exp Nephrol. 2011;15:248–57.CrossRefPubMed Akizawa T, Makino H, Matsuo S, Watanabe T, Imai E, Nitta K, et al. Management of anemia in chronic kidney disease patients: baseline findings from Chronic Kidney Disease Japan Cohort Study. Clin Exp Nephrol. 2011;15:248–57.CrossRefPubMed
Metadata
Title
Impact of hemoglobin levels on renal and non-renal clinical outcomes differs by chronic kidney disease stages: the Gonryo study
Authors
Tae Yamamoto
Mariko Miyazaki
Masaaki Nakayama
Gen Yamada
Masato Matsushima
Mistuhiro Sato
Toshinobu Sato
Yoshio Taguma
Hiroshi Sato
Sadayoshi Ito
Publication date
01-08-2016
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 4/2016
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-015-1190-3

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