1. ¹Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China
2. ²Tianjin Medical University, Tianjin, China
3. ³Molecular Cardiology, Nephrology and Hypertension, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA

Correspondence: Yiqing Zhou, Cyrus Tang Hematology Center, First Affiliated Hospital, Soochow University, Suzhou, Jiangsu 215007, China. E-mail: zhou3560@roadrunner.com; Qingyu Wuc, Molecular Cardiology/Nephrology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. E-mail: wuq@ccf.org

Received 5 May 2009; Revised 17 June 2009; Accepted 28 July 2009; Published online 23 September 2009.

Abstract

Iron deficiency anemia is a common complication in end-stage renal disease (ESRD) and impairs the therapeutic efficacy of recombinant erythropoietin. Oral or parental iron supplements usually are effective in treating iron deficiency anemia. Some patients, however, respond poorly to iron supplements and are diagnosed as having iron-refractory iron deficiency anemia. The condition exacerbates ESRD but its underlying mechanism was unclear. Hepcidin is a central player in iron homeostasis. It downregulates the iron exporter ferroportin, thereby inhibiting iron absorption, release, and recycling. In ESRD, plasma hepcidin levels are elevated, which contributes to iron deficiency in patients. Matriptase-2, a liver transmembrane serine protease, has been found to have a major role in controlling hepcidin gene expression. In mice, defects in the Tmprss6 gene encoding matriptase-2 result in high hepcidin expression and cause severe microcytic anemia. Similarly, mutations in the human TMPRSS6 gene have been identified in patients with iron-refractory iron deficiency. Thus, matriptase-2 is critical for iron homeostasis and may have an important role in ESRD.