Growth differentiation factor 15 is related to anemia and iron metabolism in heart allograft recipients and patients with chronic heart failure.

BACKGROUND: Growth differentiation factor (GDF) 15 was recently identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. The aim of this study was to assess GDF15 levels and its correlation with iron parameters in 134 stable heart transplant recipients compared with 157 patients with chronic heart failure (CHF).

METHODS: Complete blood count, urea, creatinine, lipids, fasting glucose, and iron status were studied with the use of standard laboratory methods. We assessed GDF15, hepcidin, and soluble transferrin receptor (sTfR) with commercially available assays.

RESULTS: Mean levels of GDF15 and hepcidin were significantly higher in heart allograft recipients compared with patients with chronic heart failure (P < .001). GDF15 was significantly higher in patients with anemia compared with nonanemic counterparts in both groups. In univariate analysis in heart transplant recipients, GDF15 was related to kidney function, age, time after transplantation, hepcidin, sTfR, hemoglobin, transferrin saturation, ejection fraction (EF), and New York Heart Association functional class. GDF15 was not related to serum iron or ferritin in both groups. In multivariate analysis, sTfR, creatinine, and age were found to be predictors of GDF15. In univariate analysis in CHF patients, GDF15 was related to creatinine, erythrocyte count, hemoglobin, hepcidin, and total iron binding capacity and tended to correlate with EF. In multivariate analysis, hepcidin, creatinine, and EF were found to be predictors of GDF15 in CHF.

CONCLUSIONS: GDF15, by affecting iron status, might be involved in the pathogenesis of anemia in patients with cardiovascular pathology.