Anaemia management and mortality risk in newly visiting patients with chronic kidney disease in Japan: The CKD-ROUTE study

Nephrology (Carlton). 2015 Sep;20(9):601-8. doi: 10.1111/nep.12493.


Aim: To investigate the association between iron deficiency anaemia and mortality risk and assess the changes in anaemia and iron status after primary management by a nephrologist.

Methods: In this prospective cohort study, we stratified 951 non-dialysis chronic kidney disease (CKD) G2-G5 patients newly visiting 16 nephrology centres into four groups according to the presence of anaemia with or without iron deficiency. All-cause mortality, cardiovascular (CV)-related mortality, and a change in anaemia and iron status after specialized primary care were the endpoints evaluated.

Results: During a median follow-up time of 19 months, the number of all-cause deaths and CV-related deaths were 56 and 26, respectively. Compared with the control group, the groups with isolated anaemia and iron deficiency anaemia had significantly higher all-cause mortalities (isolated anaemia: hazard ratio (HR), 3.37; 95% confidence intervals (CI), 1.76-6.44; iron deficiency anaemia: HR, 3.11; 95% CI, 1.21-8.01) and CV-related mortalities (isolated anaemia: HR, 3.64; 95% CI, 1.36-9.73; iron deficiency anaemia: HR, 3.86; 95% CI, 1.11-13.41). In the isolated anaemia group, erythropoietin-stimulating agent (ESA) prescriptions significantly increased to approximately 70%. However, in patients with both anaemia and iron deficiency, iron prescriptions only increased to 48.1%.

Conclusions: Iron deficiency anaemia and isolated anaemia were associated with all-cause and CV-related mortality. The absence of relative increase in iron prescriptions suggests that iron deficiency should be accurately assessed and iron supplementation should be appropriately used to manage anaemia in non-dialysis patients with CKD.

Keywords: anaemia; cardiovascular disease; chronic kidney disease; iron deficiency; mortality.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anemia, Iron-Deficiency / blood
  • Anemia, Iron-Deficiency / diagnosis
  • Anemia, Iron-Deficiency / drug therapy*
  • Anemia, Iron-Deficiency / mortality*
  • Biomarkers / blood
  • Cardiovascular Diseases / mortality
  • Cause of Death
  • Chi-Square Distribution
  • Dietary Supplements*
  • Disease Progression
  • Female
  • Hematinics / therapeutic use*
  • Humans
  • Iron / blood
  • Iron / therapeutic use*
  • Japan / epidemiology
  • Kidney Failure, Chronic / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Primary Health Care
  • Proportional Hazards Models
  • Prospective Studies
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / mortality*
  • Renal Insufficiency, Chronic / therapy*
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Hematinics
  • Iron