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Principal Investigator: Alexander James Kula
Organization: LURIE CHILDREN'S HOSPITAL OF CHICAGO
Fiscal Year: 2024
Award: $191,143
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
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.
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