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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK081677-03
Application #
8109419
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2009-08-24
Project End
2014-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
3
Fiscal Year
2011
Total Cost
$137,160
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Allegretti, Andrew S; Hundemer, Gregory; Chorghade, Rajeev et al. (2015) Perspectives of continuous renal replacement therapy in the intensive care unit: a paired survey study of patient, physician, and nurse views. BMC Nephrol 16:105
Bhan, Ishir; Dobens, Dorothy; Tamez, Hector et al. (2015) Nutritional vitamin D supplementation in dialysis: a randomized trial. Clin J Am Soc Nephrol 10:611-9
Quraishi, Sadeq A; De Pascale, Gennaro; Needleman, Joseph S et al. (2015) Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis: A Randomized, Placebo-Controlled Trial. Crit Care Med 43:1928-37
Quraishi, Sadeq A; Bittner, Edward A; Blum, Livnat et al. (2014) Prospective study of vitamin D status at initiation of care in critically ill surgical patients and risk of 90-day mortality. Crit Care Med 42:1365-71
Leaf, David E; Waikar, Sushrut S; Wolf, Myles et al. (2013) Dysregulated mineral metabolism in patients with acute kidney injury and risk of adverse outcomes. Clin Endocrinol (Oxf) 79:491-8
Bhan, Ishir; Tamez, Hector; Thadhani, Ravi (2013) Impact of new vitamin D data on future studies and treatment. Curr Opin Nephrol Hypertens 22:377-82
Allegretti, Andrew S; Steele, David J R; David-Kasdan, Jo Ann et al. (2013) Continuous renal replacement therapy outcomes in acute kidney injury and end-stage renal disease: a cohort study. Crit Care 17:R109
Bhan, Ishir; Powe, Camille E; Berg, Anders H et al. (2012) Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int 82:84-9
Bhan, Ishir; Camargo Jr, Carlos A; Wenger, Julia et al. (2011) Circulating levels of 25-hydroxyvitamin D and human cathelicidin in healthy adults. J Allergy Clin Immunol 127:1302-4.e1
Powe, Camille E; Ricciardi, Catherine; Berg, Anders H et al. (2011) Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 26:1609-16

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