Association of Renal Tubular Damage With Cardio-Renal Anemia Syndrome in Patients With Heart Failure

Int J Cardiol. 2014 May 1;173(2):222-8. doi: 10.1016/j.ijcard.2014.02.044. Epub 2014 Feb 28.


Background: Cardio-renal anemia syndrome (CRAS) has begun to gather attention as a vicious circle since chronic heart failure (CHF), chronic kidney disease (CKD), and anemia are all able to be caused and exacerbated by each other. However, it remains unclear whether renal tubular damage (RTD), another type of kidney dysfunction, is associated with this vicious circle. The aim of the present study was to assess the association of RTD with CRAS in patients with CHF.

Methods and results: We included 300 consecutive patients with CHF. RTD was defined as a urinary β2-microglobulin to creatinine ratio ≥ 300 μg/g. Patients with RTD had lower serum iron and higher levels of high sensitivity C-reactive protein than those without it. Multivariate logistic analysis showed that RTD was closely associated with anemia in patients with CHF, after adjustment for confounding factors. During a median period of 1,098 days, there were 86 cardiac events, including 14 cardiac deaths and 72 re-hospitalizations for worsening heart failure. Net reclassification improvement was significantly improved by addition of RTD to the model including age, New York Heart Association functional class, brain natriuretic peptide, anemia, and CKD. All patients were divided into 3 groups: CRAS+RTD group, CRAS group, and control group. Kaplan-Meier analysis demonstrated that CRAS+RTD had the greatest risk in patients with CHF.

Conclusions: RTD was associated with normocytic anemia, accompanying iron deficiency and inflammation. RTD added prognostic information to conventional CRAS, suggesting the importance of RTD in cardio-renal anemia interaction.

Keywords: Anemia; Cardio-renal anemia syndrome; Heart failure; Renal tubular damage.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anemia, Iron-Deficiency / epidemiology
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Cardio-Renal Syndrome / epidemiology*
  • Cardio-Renal Syndrome / metabolism
  • Confounding Factors, Epidemiologic
  • Creatinine / urine
  • Female
  • Heart Failure / epidemiology*
  • Humans
  • Iron / blood
  • Kaplan-Meier Estimate
  • Kidney Tubules / metabolism*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • beta 2-Microglobulin / urine


  • Biomarkers
  • beta 2-Microglobulin
  • C-Reactive Protein
  • Creatinine
  • Iron