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Mentored patient-oriented research of novel mechanisms for cardiovascular disease in patients with chronic kidney disease

Award Number: K24HL150235
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/01/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Mentored patient-oriented research of novel mechanisms for cardiovascular disease in patients with chronic kidney disease - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	000	5	5/6/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $114,404 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	000	5	12/14/2023	NON-COMPETING CONTINUATION	$114,404
														Subtotal = $114,404

Issue Date FY: 2023 ( Subtotal = $115,490 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	000	4	1/12/2023	NON-COMPETING CONTINUATION	$115,490
														Subtotal = $115,490

Issue Date FY: 2022 ( Subtotal = $116,349 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	000	3	12/29/2021	NON-COMPETING CONTINUATION	$116,349
														Subtotal = $116,349

Issue Date FY: 2021 ( Subtotal = $117,507 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	000	2	4/7/2021	NON-COMPETING CONTINUATION	$117,507
														Subtotal = $117,507

Issue Date FY: 2020 ( Subtotal = $118,605 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	000	1	12/15/2019	NEW	$118,605
														Subtotal = $118,605

Grand Total All Awards = $582,355

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Mentored patient-oriented research of novel mechanisms for cardiovascular disease in patients with chronic kidney disease

Award Number: K24HL150235

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/01/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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