Joshua J. Zaritsky, MD, PhD

Assistant Professor

Pediatrics Division of Pediatric Nephrology
Mattel Children's Hospital, UCLA

Project: Hepcidin and the anemia of chronic kidney disease

Mentors:
Isidro Salusky, MD - UCLA
Tomas Ganz, MD, PhD - UCLA
Kamyar Kalantar-Zadeh, MD, MPH, PhD - Lundquist/Harbor-UCLA Medical Center

Multidisciplinary Expertise:
Nephrology, Pediatrics

Project Description:
Erythropoiesis-stimulating agents (ESA)(drugs used to spur red blood cell production), are an important component of anemia therapy in patients with chronic kidney disease (CKD). ESA hyporesponsiveness, however, occurs frequently and is often associated with iron deficiency and inflammation as well as poor outcomes. Given the urgent need to explore novel approaches that can allow ESA dose reduction as recently recommended by the FDA, it is crucial to understand the molecular mechanisms that link inflammation, iron balance and erythropoiesis in CKD. Hepcidin, a protein produced in the liver, is a key regulator of iron homeostasis. Preliminary data indicates that hepcidin accumulates in CKD, making it likely that hepcidin plays a major role in the anemia of CKD as well as ESA hyporesponsiveness. This project aims to expand our knowledge of hepcidin biology in the setting of CKD. It will examine two hypotheses: (1) Does progressive loss of kidney function directly lead to increased hepcidin levels? and (2) Do these increased hepcidin levels contribute to iron restriction and anemia in experimental animals with CKD? This project will provide crucial knowledge as to whether hepcidin contributes to the anemia of renal disease and ESA hyporesponsiveness and thus will help to optimize anemia treatment of CKD.