The purpose of this proposal is to support protected time for Dr. Sharon Moe to continue her own clinical research and to mentor new investigators in the musculoskeletal diseases observed in dialysis patients. Dr Moe has a proven track record in patient oriented research with strong extramural funding of several projects. She has a successful record in mentoring Nephrology Fellows in this area, and is active at both the divisional and Departmental levels in clinical research education. She has been active in the development of a core curriculum and will serve as a course director. Thus, her dedication to mentoring young investigators is strong. The proposed Investigator initiated projects examine two important diseases that affect the musculoskeletal system in dialysis patients: Renal Osteodystrophy and beta2-microglobulin amyloidosis. The first project aims to evaluate the immunomodulatory effects of the new Vitamin D derivative paricalcitol in patients not receiving vitamin D due to low levels of parathyroid hormone. The study is a placebo controlled trial with ex-vivo evaluations of lymphocyte function and in vivo evaluations of B and T cell function. The second study is a cross-over study evaluating the effect of a new phosphate binder, sevelamer, on calcium balance in peritoneal dialysis patients. The study will compare calcium balance and parathyroid function in peritoneal dialysis patients with adynamic bone disease. The third study involves the examination of adhesion molecules in the pathogenesis of beta2-microglobulin amyloidosis utilizing fibroblasts and monocytes isolated from control patients, patients with osteoarthritis, and patients with renal failure. The final study evaluates monocycline as a possible therapy for beta2-microglobulin amyloidosis in a pilot study that also will evaluate the feasibility of measuring response to therapy with several different indicators of amyloid deposition and patient quality of life. These important studies into the pathogenesis of musculoskeletal disorders in dialysis patients are important studies that will advance our understanding and management of these disabling disease. In addition, they serve as an excellent environment to mentor young investigators. These studies, Dr. Moe, and the strong clinical research environment at Indiana University should prove fertile for the development of future investigators in patient oriented research.
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