Vitamin D deficiency is highly prevalent in patients with advanced chronic kidney disease (CKD). Cardiovascular disease (CVD) and infection are the top causes of morbidity and mortality in CKD and end- stage renal disease (ESRD). Evidence generated by the candidate's (Ravi Thadhani, MD, MPH) laboratory has linked CVD progression and altered immune response to inadequate vitamin D levels in CKD/ESRD. Under Dr. Thadhani's direction, a comprehensive patient-oriented research program seeks to investigate the relationship between vitamin D biology and supplementation strategies in terms of mechanistic and clinically relevant endpoints. This application describes three unique aims in three studies (each backed by separate funding sources) that will be pursued by the candidate and his trainees: (1) in DIVINE - an NIH sponsored trial of nutritional vitamin D - his team will determine whether nutritional vitamin D deficiency in ESRD patients leads to altered macrophage function and ex-vivo response to infection;(2) in PRIMO - an industry sponsored trial of active vitamin D and left ventricular hypertrophy [LVH], diastolic function, and cardiac hospitalization in patients with stage 3/4 CKD - his team will determine if baseline levels of 25-hydroxy vitamin D (25D) and fibroblast growth factor-23 (FGF-23) are linked to progression or lack of regression of LVH;and (3) in LUCID - a prospective cohort of incident ESRD subjects supported by the Canadian Institutes of Health - his team will examine whether active vitamin D leads to excess coronary artery calcification. By supporting the candidate's request for this K24 award, important patient-oriented questions will be addressed. Moreover, Dr. Thadhani, with an exemplary record of mentorship, teaching and research, will be afforded the necessary protected time to mentor individuals who comprise a new generation of clinical research fellows and students in Nephrology.

Public Health Relevance

Cardiovascular disease and infection are the primary causes of death in individuals with advanced chronic kidney disease (CKD). Evidence suggests that vitamin D deficiency, which is both highly prevalent and profound in CKD patients, may influence the rate of cardiovascular disease progression and may also mediate immune response to infection in CKD. We have established a comprehensive patient oriented research program that is engaged in testing well-defined hypotheses in patients with late and end-stage renal disease linking vitamin D biology to clinically relevant endpoints. In addition to serving th public health by investigating important patient-oriented questions, this program is a platform for intensive training of clinical research fellows and students by Ravi Thadhani, MD, MPH, whose mentoring efforts will be supported by this K24 award.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24DK094872-02
Application #
8459458
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2012-04-15
Project End
2017-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$109,186
Indirect Cost
$8,088
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Bentley-Lewis, Rhonda; Powe, Camille; Ankers, Elizabeth et al. (2014) Effect of race/ethnicity on hypertension risk subsequent to gestational diabetes mellitus. Am J Cardiol 113:1364-70
Welles, Christine C; Whooley, Mary A; Karumanchi, S Ananth et al. (2014) Vitamin D deficiency and cardiovascular events in patients with coronary heart disease: data from the Heart and Soul Study. Am J Epidemiol 179:1279-87
Kalim, Sahir; Karumanchi, S Ananth; Thadhani, Ravi I et al. (2014) Protein carbamylation in kidney disease: pathogenesis and clinical implications. Am J Kidney Dis 64:793-803
Bello, Aminu K; Stenvinkel, Peter; Lin, Meng et al. (2014) Serum testosterone levels and clinical outcomes in male hemodialysis patients. Am J Kidney Dis 63:268-75
Nigwekar, Sagar U; Solid, Craig A; Ankers, Elizabeth et al. (2014) Quantifying a rare disease in administrative data: the example of calciphylaxis. J Gen Intern Med 29 Suppl 3:S724-31
Nigwekar, Sagar U; Tamez, Hector; Thadhani, Ravi I (2014) Vitamin D and chronic kidney disease-mineral bone disease (CKD-MBD). Bonekey Rep 3:498
Bentley-Lewis, Rhonda; Dawson, Deanna L; Wenger, Julia B et al. (2014) Placental histomorphometry in gestational diabetes mellitus: the relationship between subsequent type 2 diabetes mellitus and race/ethnicity. Am J Clin Pathol 141:587-92
Powe, Camille E; Karumanchi, S Ananth; Thadhani, Ravi (2014) Vitamin D-binding protein and vitamin D in blacks and whites. N Engl J Med 370:880-1
Berg, Anders H; Drechsler, Christiane; Wenger, Julia et al. (2013) Carbamylation of serum albumin as a risk factor for mortality in patients with kidney failure. Sci Transl Med 5:175ra29
de Boer, Ian H; Thadhani, Ravi (2013) Vitamin D deficiency: consequence or cause of CKD? Clin J Am Soc Nephrol 8:1844-6

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