Dr. Bhan is a physician with a diverse research background spanning both basic and clinical science, supplemented by formal training in public health, nephrology, and medical informatics. His long-term career goal is to use basic laboratory findings to guide novel clinical studies aimed at improving outcomes in patients with chronic kidney disease (CKD). This research-oriented career will be complemented by continued work in applied medical informatics and clinical medicine. Research training will be aided by the extensive resources of Massachusetts General Hospital, mentorship of veteral clinical scientist Ravi Thadhani, an advisory committee of experienced senior scientists, and a relevant didactic program in biostatistics, epidemiology, and research design at the Harvard School of Public Health. Dr. Bhan's goal over the next 5 years is to develop an independent research career focused on infectious disease, the second-leading cause of death in the CKD population. This project aims to define a specific mechanism that may contribute to the increased risk of morbidity and mortality in these patients. Individuals with CKD are deficient in the active form of vitamin D and thus may be deficient in human cathelicidin (hCAP18), a vitamin-D regulated protein with potentent antibacterial properties. Treatment with vitamin D has been associated with a reduce risk of all-cause, cardiovascular, and infection-associated mortality. An important mechanism may be the upregulation of hCAP18. This project will use a large (n=10,044) cohort of incident hemodialysis patients which provides blood samples, demographic and clinical data to examine if hCAP18 levels are linked with mortality. In addition, a general clinical research center (GCRC)-based study will elucidate the relationship between systemic levels of hCAP18 and vitamin D in populations with varying degrees of renal function. The ability of two different forms of vitamin D therapy (ergocalciferol and calcitriol) to modify hCAP18 levels will be determined. PUBLIC HEALTH RELEVANCE: This research examines if an increased risk of death associated with kidney disease is related to deficiency of a specific protein, and whether this deficiency can be corrected with inexpensive and well-tolerated vitamin D therapy.