TY - JOUR
T1 - Hepcidin-25 in Chronic Hemodialysis Patients Is Related to Residual Kidney Function and Not to Treatment with Erythropoiesis Stimulating Agents
AU - van der Weerd, Neelke C.
AU - Grooteman, Muriel P. C.
AU - Bots, Michiel L.
AU - van den Dorpel, Marinus A.
AU - den Hoedt, Claire H.
AU - Mazairac, Albert H. A.
AU - Nubé, Menso J.
AU - Penne, E. Lars
AU - Gaillard, Carlo A.
AU - Wetzels, Jack F. M.
AU - Wiegerinck, Erwin T.
AU - Swinkels, Dorine W.
AU - Blankestijn, Peter J.
AU - ter Wee, Piet M.
AU - AUTHOR GROUP
AU - Koopman, M. G.
AU - Kooistra, M.
AU - van Jaarsveld, B.
AU - Feith, G. W.
AU - van Buren, M.
AU - Hoogeveen, E. K.
AU - van de Ven, P. J.
AU - Hovinga, T. K. Kremer
AU - Bax, W. A.
AU - Groeneveld, J. O.
AU - Reichert, L. J. M.
AU - Huussen, J.
AU - van Hamersvelt, H. W.
AU - Boer, W. H.
AU - van Kuijk, W. H.
AU - Vervloet, M. G.
AU - Wauters, I. M. P. M. J.
PY - 2012
Y1 - 2012
N2 - Hepcidin-25, the bioactive form of hepcidin, is a key regulator of iron homeostasis as it induces internalization and degradation of ferroportin, a cellular iron exporter on enterocytes, macrophages and hepatocytes. Hepcidin levels are increased in chronic hemodialysis (HD) patients, but as of yet, limited information on factors associated with hepcidin-25 in these patients is available. In the current cross-sectional study, potential patient-, laboratory-and treatment-related determinants of serum hepcidin-20 and -25, were assessed in a large cohort of stable, prevalent HD patients. Baseline data from 405 patients (62% male; age 63.7 +/- 13.9 [mean SD]) enrolled in the CONvective TRAnsport STudy (CONTRAST; NCT00205556) were studied. Predialysis hepcidin concentrations were measured centrally with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patient-, laboratory-and treatment related characteristics were entered in a backward multivariable linear regression model. Hepcidin-25 levels were independently and positively associated with ferritin (p <0.001), hsCRP (p <0.001) and the presence of diabetes (p = 0.02) and inversely with the estimated glomerular filtration rate (p = 0.01), absolute reticulocyte count (p = 0.02) and soluble transferrin receptor (p <0.001). Men had lower hepcidin-25 levels as compared to women (p = 0.03). Hepcidin-25 was not associated with the maintenance dose of erythropoiesis stimulating agents (ESA) or iron therapy. In conclusion, in the currently studied cohort of chronic HD patients, hepcidin-25 was a marker for iron stores and erythropoiesis and was associated with inflammation. Furthermore, hepcidin-25 levels were influenced by residual kidney function. Hepcidin-25 did not reflect ESA or iron dose in chronic stable HD patients on maintenance therapy. These results suggest that hepcidin is involved in the pathophysiological pathway of renal anemia and iron availability in these patients, but challenges its function as a clinical parameter for ESA resistance
AB - Hepcidin-25, the bioactive form of hepcidin, is a key regulator of iron homeostasis as it induces internalization and degradation of ferroportin, a cellular iron exporter on enterocytes, macrophages and hepatocytes. Hepcidin levels are increased in chronic hemodialysis (HD) patients, but as of yet, limited information on factors associated with hepcidin-25 in these patients is available. In the current cross-sectional study, potential patient-, laboratory-and treatment-related determinants of serum hepcidin-20 and -25, were assessed in a large cohort of stable, prevalent HD patients. Baseline data from 405 patients (62% male; age 63.7 +/- 13.9 [mean SD]) enrolled in the CONvective TRAnsport STudy (CONTRAST; NCT00205556) were studied. Predialysis hepcidin concentrations were measured centrally with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patient-, laboratory-and treatment related characteristics were entered in a backward multivariable linear regression model. Hepcidin-25 levels were independently and positively associated with ferritin (p <0.001), hsCRP (p <0.001) and the presence of diabetes (p = 0.02) and inversely with the estimated glomerular filtration rate (p = 0.01), absolute reticulocyte count (p = 0.02) and soluble transferrin receptor (p <0.001). Men had lower hepcidin-25 levels as compared to women (p = 0.03). Hepcidin-25 was not associated with the maintenance dose of erythropoiesis stimulating agents (ESA) or iron therapy. In conclusion, in the currently studied cohort of chronic HD patients, hepcidin-25 was a marker for iron stores and erythropoiesis and was associated with inflammation. Furthermore, hepcidin-25 levels were influenced by residual kidney function. Hepcidin-25 did not reflect ESA or iron dose in chronic stable HD patients on maintenance therapy. These results suggest that hepcidin is involved in the pathophysiological pathway of renal anemia and iron availability in these patients, but challenges its function as a clinical parameter for ESA resistance
U2 - https://doi.org/10.1371/journal.pone.0039783
DO - https://doi.org/10.1371/journal.pone.0039783
M3 - Article
C2 - 22808058
SN - 1932-6203
VL - 7
SP - e39783
JO - PLOS ONE
JF - PLOS ONE
IS - 7
M1 - e39783
ER -