Cardiovascular risk assessment and management in the paediatric population is a relatively uncharted territory. However, atherogenesis starts during childhood, making childhood and adolescence an important window of opportunity to prevent atherosclerotic cardiovascular disease (ASCVD) later in life. An emerging group at risk for early ASCVD are children with chronic conditions. This paper describes the rationale, design and methods for the Secondary Manifestations of ARTerial diseases in the Young with a chronic condition (SMART-Youth) study. This study aims to identify disease-associated and lifestyle-associated cardiovascular risk factors for preclinical atherosclerosis in children with a chronic condition. The results of this study may fuel development of tailored cardiovascular risk assessment and management strategies in children at-risk.

This is a prospective longitudinal cohort study including children aged 8–18 years with various chronic conditions (cystic fibrosis, juvenile idiopathic arthritis, systemic autoimmune disease, chronic kidney disease, primary immunodeficiency, autoinflammatory conditions, inflammatory bowel disease, congenital heart disease, premature birth, fetal growth restriction and children with persistent somatic symptoms) at the Wilhelmina Children’s Hospital of the University Medical Center Utrecht in The Netherlands. Assessment of cardiovascular risk factors includes blood pressure, body mass index, visceral and subcutaneous abdominal adipose tissue, nutrition, physical activity, stress, circulating lipids, HbA1c and C-reactive protein measurements. Preclinical atherosclerosis is measured by carotid intima-media thickness, carotid distension and carotid-femoral pulse wave velocity. These assessments are performed at baseline, 2-year follow-up and 17–18 years of age. Enrollment runs from August 2024 onwards, with a minimal study duration of 15 years and an estimated final sample of more than 2000 children. State-of-the-art regression-based methods will be used to examine the association of cardiovascular risk factors and preclinical atherosclerosis. Longitudinal data analysis methods will be used to model these associations over time.

Ethical approval was granted by the Medical Ethics Review Board of the University Medical Center Utrecht (NL84874.041.23). Written informed consent by participants and their parents is required for participation. Collected data will be made available to researchers upon reasonable request to the Steering Committee. Study findings will be disseminated through peer-reviewed publications, presentations at scientific meetings and meetings with patient organisations.

Recent studies have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease in people at high cardiovascular risk, with or without type 2 diabetes. To date, all published studies have excluded kidney transplant recipients (KTRs). The Dapagliflozin Early After Kidney Transplantation (DEAK) study aims to prospectively evaluate the effects of the SGLT2 inhibitor dapagliflozin on kidney function, histopathology and metabolic outcomes among de novo KTRs.

This nationwide, investigator-initiated, single-transplant-centre, randomised, placebo-controlled, prospective clinical trial with two parallel groups aims to enrol 330 de novo adult KTRs (aged 18–75 years) with an estimated glomerular filtration rate (eGFR) of at least 25 mL/min/1.73 m². Participants are enrolled 6–8 weeks after transplantation and randomised 1:1 to receive dapagliflozin 10 mg/day or placebo for 3 years. Recipients with conditions that may intermittently affect kidney function, such as recent acute rejection or ongoing infection, are ineligible for inclusion.

The primary endpoint of the study is the difference in the chronic eGFR slope between treatment groups over 3 years, estimated using the European Kidney Function Consortium equation. Secondary and safety endpoints include changes in measured GFR (iohexol clearance), urinary albumin/creatinine ratio, blood pressure, infections and safety clinical chemistry. Exploratory endpoints evaluated after 1.5 years include changes in body composition and glucose tolerance; between-group differences in urinary metabolomics; transplant kidney biopsy inflammation and fibrosis scores (n=140) and kidney biopsy messenger RNA and protein expression (n=50). The protocol also includes a 10-year poststudy registry follow-up of eGFR slope, cardiovascular events and graft and patient survival.

The study protocol (EudraCT number: 2022-002428-10) has been approved by the Norwegian Medical Products Agency, the Regional Committee for Medical Research Ethics in Southeast Norway (REK Southeast number 426076) and by the data protection offices at the participating hospitals. The main results will be published in international, peer-reviewed scientific journals.

NCT05788276.