Thursday, April 3, 2025
4/3/2025
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.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).