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.
Department of Cardiovascular Surgery and Transplantology, Jagiellonian University Medical College, John Paul II Hospital, Cracow, Poland. Electronic address: piotr.przybylowski@uj.edu.pl.
P
P
Przybyłowski
Department of Cardiovascular Surgery and Transplantology, Jagiellonian University Medical College, John Paul II Hospital, Cracow, Poland.
G
G
Wasilewski
Department of Invasive Cardiology, Medical University, Bialystok, Poland.
H
H
Bachorzewska-Gajewska
2nd Department of Nephrology, Medical University of Bialystok, Poland.
K
K
Golabek
2nd Department of Nephrology, Medical University of Bialystok, Poland.
S
S
Dobrzycki
2nd Department of Nephrology, Medical University of Bialystok, Poland.
J
J
Małyszko
D000328:Adult; D000368:Aged; D064591:Allografts; D000740:Anemia / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D003404:Creatinine; D004906:Erythrocyte Count; D004920:Erythropoiesis; D005260:Female; D005293:Ferritins / Q000097:blood*; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006333:Heart Failure / Q000097:blood; D016027:Heart Transplantation; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000150:complications; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000097:blood
D055436:Growth Differentiation Factor 15; D064451:Hepcidins; D011990:Receptors, Transferrin; D005293:Ferritins; D003404:Creatinine; D007501:Iron