PROJECT SUMMARY
Tamara Isakova, MD, MMSc is applying for the K24 Midcareer Investigator Award in Patient-Oriented
Research (POR). She is an Associate Professor of Medicine in the Division of Nephrology at the Northwestern
University Feinberg School of Medicine. She directs the Center for Translational Metabolism and Health within
the Institute for Public Health and Medicine and the Clinical and Translational Core of the O'Brien Kidney Core
Research Center. Dr. Isakova's research is focused on developing the evidence for novel approaches to
improve cardiovascular disease outcomes in patients with chronic kidney disease (CKD). She has expertise in
epidemiologic studies, POR and multi-center clinical trials, and she has served as a scientific mentor for
medical students, residents, fellows, and junior faculty. Support from the K24 will provide Dr. Isakova with
protected time 1) to devote more time to mentoring a diverse group of young investigators in POR; 2) to
improve her POR mentoring skills through mentor training and guidance from senior mentors; 3) to expand into
new scientific areas through cross-disciplinary collaborations; 4) to replenish support for her research program
through new NIH funding; and 5) to increase involvement in clinical trials, which will allow her to assume
leadership in collaborative POR. A large body of evidence implicates disordered mineral metabolism as a
mechanistic contributor to the pathogenesis of cardiovascular disease in CKD. The current proposal builds
upon this scientific premise and extends the R01-supported work of the PI. Project 1 leverages ongoing work
in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial, which is a multi-center,
randomized, double-blinded, placebo-controlled trial that tested the hypothesis that nicotinamide (blocks active
phosphate transport in the gut) and lanthanum carbonate (phosphate binder) would safely lower serum
phosphate and fibroblast growth factor (FGF23) levels compared to placebo over 12 months in 205 patients
with CKD stages 3b–4. With support from the K24, the PI will ascertain whether the efficacy of lanthanum
carbonate was more pronounced in certain subgroups, determine the relationship of phosphate and FGF23
lowering with myocardial strain, and investigate the effects of interventions on downstream products of
nicotinamide and other metabolites and on T50, a calcification biomarker. Project 2 leverages ongoing work in
the Chronic Renal Insufficiency Cohort (CRIC) Study, which is an observational study of ~4,000 patients with
CKD stages 2 – 4. With support from the K24, the PI will determine whether a combined assessment of T50
and other intermediate cardiovascular disease end-points could help identify a CKD-specific cardiovascular
disease phenotype, and she will examine possible modifiable determinants of deoxycholic acid, a secondary
bile acid implicated in the pathogenesis of vascular calcification in CKD. Conduct of the proposed Aims will
advance the field of non-traditional risk factors for cardiovascular disease, suggest potential therapeutic
approaches that the PI will test in future interventional studies and will provide a fertile ground for POR training.