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Urinary Hepcidin Excretion in Patients with Myelodysplastic Syndrome (MDS) and Myelofibrosis (MF).

2006; Elsevier BV; Volume: 108; Issue: 11 Linguagem: Inglês

10.1182/blood.v108.11.2620.2620

1528-0020

Asher Winder, Rafi Lefkowitz, Hussam Ghoti, Merav Leiba, Tomas Ganz, Elizabeta Nemeth, E. A. Rachmilewitz,

Erythropoietin and Anemia Treatment

Abstract One of the main features of patients with Myelodysplastic Syndrome (MDS) is severe anemia which requires multiple blood transfusions with consequent iron overload. Moreover, iron metabolism is impaired particularly in refractory anemia with ring sideroblasts (RARS). Hepcidin is a small, cysteine-rich cationic peptide produced by hepatocytes, secreted into plasma and excreted in the urine. Hepcidin control iron absorption in the gut, release of iron from macrophages and is a key regulator of iron metabolism. Patients with iron overload have elevated urinary hepcidin levels but patients with anemia or increased erythropoietic precursors have suppressed hepcidin. The purpose of this study was to measure hepcidin excretion in the urine of patients with MDS and Myelofibrosis (MF). The assay of urinary Hepcidin was performed by the method of Nemeth et al (J. Clin.Invest113:1271–1276, 2004) and expressed per mg urinary creatinine. The samples were obtained from 20 patients, 16 with MDS and 4 with MF. Their subtypes and age, ranging from 54 to 87 years, are shown in the table. Nine MDS patients received less than 10 units of blood and the rest, between 13 and 147 units. Seven MDS patients had ferritin levels above 1000 ng/ml and their transferrin saturation in most of them was more than 50%. The urinary excretion of hepcidin was low (less then 1 ng/mg creatinine) in 3 MDS and 3 MF patients, while in the rest, with the exception of 2 patients, the levels were less than 50 ng/mg creatinine. Although the degree of iron overload was not related directly to the subtype and to the number of blood units, in some patients mainly with RARS it was quite severe. More importantly, the urinary hepcidin excretion had a more consistent pattern of low levels in all the patients even in those with high ferritin or high transferrin saturation levels. Hepcidin concentrations correlated well with serum ferritin (r2 = 0.62 on a log-log plot) but the slope of the correlation was only 0.05 (normal ~ 1) indicating marked suppression of hepcidin relative to ferritin. Suppression of hepcidin in MDS and MF suggests that hepcidin deficiency could worsen the maldistribution of iron from the nontoxic form in macrophages to toxic forms in parenchymal cells, and that intestinal iron absorption as well as transfusional iron could contribute to their iron overload. Age Gender Diagnosis/ MDS WHO subtype No. of transfused PC Transferrin saturation % Ferritin ng/ml Hepcidin ng/mg creat 76 F RA 7 65 422 32 76 M RA 2 28 87 10 76 M RA 0 44 1350 20 65 F RA 0 43 420 24 69 M RARS 147 87 5600 137 69 F RARA 76 45 2100 49 84 F RARS 87 57 4450 16 77 F RCMD 4 16 90 <1 75 M RCMD 4 88 307 21 77 F RCMD 65 48 2870 138 72 M RAEB I 5 44 102 <1 87 M RAEB I 62 87 3190 48 77 M RAEB II 13 20 152 20 79 M RAEB II 0 26 202 <1 75 F RAEB II 4 9 104 23 71 M RAEB II 80 53 2100 35 68 F MF 17 17 111 13 73 M MF 26 27 618 27 71 F MF 7 5 19 <1 54 F MF 0 12 42 <1