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Advancing the Approach to Subclinical Diastolic Dysfunction in Youth with Chronic Kidney Disease

Award Number: K23DK138313
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/16/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Advancing the Approach to Subclinical Diastolic Dysfunction in Youth with Chronic Kidney Disease - Project Summary: Dr. Alex Kula, MD, MHS, is an Assistant Professor in the Department of Pediatrics at Northwestern University Feinberg School of Medicine (NU) and attending physician in the Division of Pediatric Nephrology at the Ann and Robert H. Lurie Children’s Hospital of Chicago (LCH). The K23 award will help Dr. Kula become an independent physician-scientist who applies patient-oriented research (POR) methods to advance our understanding and treatment of subclinical cardiovascular disease (CVD) in youth with chronic kidney disease (CKD). Evidence of subclinical CVD is present in youth with CKD, and risk for CVD is carried and compounded into adulthood. Adults with CKD are at notably high risk for heart failure with preserved ejection fraction (HFpEF). Transition from subclinical diastolic dysfunction to symptomatic HFpEF may be prevented with medications, including sodium glucose co-transporter 2 inhibitors (SGLT2i). Yet, advanced echocardiographic parameters used to identify diastolic dysfunction in adults have not been studied in pediatric CKD. The objective of this proposal is to leverage insights developed in adults with CKD to define a phenotype of subclinical diastolic dysfunction in pediatric CKD and to begin to test the reversibility of this phenotype in an interventional study. Dr. Kula will pursue this objective through 2 complementary POR aims: 1) an in-depth physiologic study of diastolic function at rest and with exercise using echocardiography in youth with stage 3-4 CKD (n=50) and age- and sex- matched healthy controls (n= 25); 2) a feasibility study of SGLT2i in youth with stages 3-4 CKD (n=40) that will assess primary end-points of feasibility and secondary end-points of SGLT2i effect on intermediate measures associated with risk of HFpEF. The results will impact our understanding of subclinical CVD in youth with CKD and serve as preliminary data for future R01 proposals. To ensure his transition to scientific independence, Dr. Kula has designed a robust career development plan, with the following goals: 1) gain expertise in conducting POR studies; 2) learn about cardiovascular phenotyping using echocardiography; 3) develop proficiency in clinical trials; 4) strengthen cross-disciplinary collaborations, enrich research portfolio and master scientific management skills. Dr. Kula’s scientific and training goals will be overseen by a multi-disciplinary and experienced mentorship team. His primary mentor, Dr. Tamara Isakova, is a leader in POR methods and clinical trials in nephrology. His co-mentor, Dr. Sanjiv Shah, has expertise in clinical phenotyping of diastolic dysfunction and HFpEF. External advisory committee members will provide expertise in pediatric POR, cardiac phenotyping in youth (Dr. Luc Mertens), and studies of CVD in pediatric CKD (Dr. Rulan Parekh). Dr. Kula will benefit from the exceptional institutional environment of LCH and NU, including: 1) high-volume of youth with CKD seen in LCH nephrology clinic; 2) research infrastructure of the Stanley Manne Children’s Research Institute at LCH; 3)robust and collaborative academic environment within LCH and NU. Upon completing the K23, Dr. Kula will be uniquely positioned to study interventions for CVD risk reduction in a high-risk, but understudied, population.


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: 2026 ( Subtotal = $184,335 )
2026	2026	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/23/2026	NON-COMPETING CONTINUATION	$184,335
														Subtotal = $184,335

Issue Date FY: 2025 ( Subtotal = $184,776 )
2025	2025	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/25/2025	NON-COMPETING CONTINUATION	$184,776
														Subtotal = $184,776

Issue Date FY: 2024 ( Subtotal = $191,143 )
2024	2024	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/16/2024	NEW	$191,143
														Subtotal = $191,143

Grand Total All Awards = $560,254

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Advancing the Approach to Subclinical Diastolic Dysfunction in Youth with Chronic Kidney Disease

Award Number: K23DK138313

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/16/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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