About this trial
Age related stiffening and hardening of the arteries is often a slow process, but some conditions such as chronic kidney disease (CKD), seem to increase the rate at which the arteries stiffen even during childhood. High blood pressure (BP) is well known to lead to arterial stiffening and is often seen in children and young people (CYP) with CKD.
A greater risk of arterial stiffening has been reported in children CYP with CKD compared to healthy CYP and this is thought to be related to the development of high BP, heart problems, and the worsening of kidney damage. The cause is unknown and is unlikely due to age related changes in the arterial wall seen in older adults. Potential mechanisms contributing to arterial stiffening in CYP with CKD include i) abnormalities in the interaction between the heart and the aorta (the large artery pumping blood away from the heart to the rest of the body), overactivity of the sympathetic nervous system (SNS), the body's "stress response", or iii) abnormal metabolism seen in CKD, where there are high levels of phosphate and other waste products circulating in the blood as a result of damage to the kidneys.
In this study, the investigators will use a variety of non invasive experimental methods to determine if arterial stiffening seen in CYP with CKD is due solely to increased BP, or whether the other potential factors listed above also contribute. This may help to eventually identify how to prevent or treat arterial stiffness in CYP with CKD and prevent its adverse impact on kidney and heart health in later life. The investigators will compare findings between those with CKD and an age, sex and BP matched control group. This control group will comprise CYP both with high BP (primary hypertension) and without high BP (healthy participants).
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Aged 10-25 years at study entry.
Diagnosis of CKD confirmed on at least two GFR assessments 3-months apart; eGFR will be estimated using routine bedside formulae (modified Schwartz). Participants may include those on dialysis or those with a functioning kidney transplant.
Able to tolerate study investigations including 24-hour ABPM, echocardiogram, vascular assessments and MRI.
Aged 10-25 years at study entry
Disqualifiers
Heart abnormalities or pre-existing cardiac disease including congenital heart disease, previous cardiac surgery or heart failure.
Cardiac dysrhythmia.
Inability to tolerate the required study investigations (out of office BP monitoring, applanation tonometry, cardiac MRI).
Trial population
Children and young adults with chronic kidney disease and age-, sex- and gender-matched healthy controls and those with primary hypertension.
Trial design
Cohort
Prospective
Treatments tested in this trial
Not listed
Trial groups
Trial outcomes
Primary outcomes
Difference in carotid femoral pulse wave velocity
The difference in carotid femoral pulse wave velocity (m/s) between children and young adults with CKD and age, sex and blood pressure (BP) matched controls.
Secondary outcomes
Difference in carotid femoral pulse wave velocity once blood pressure is normalised
The difference in carotid femoral pulse wave velocity (m/s) pre and post anti-hypertensive therapy in children and young adults with CKD.
Difference in sympathetic nerve activity
The difference in markers of sympathetic nerve activity between children and young people with CKD compared to age, sex and BP matched controls as follows: * Plasma catecholamines. * Pulse wave velocity (m/s) difference pre and post device guided slow breathing (DGB). * Pulse wave velocity (m/s) difference pre and post lower limb venous occlusion (LVO)
Difference in aortic pulse wave velocity
The difference in aortic pulse wave velocity (m/s) as measured by MRI between children and young adults with CKD and age, sex and BP matched controls.
Difference in cardiac output - echocardiography
The difference in cardiac output between CYP with CKD and age, sex and BP matched controls as measured by: Echocardiography
Sponsors and contacts
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King's College London
Lead sponsor
Guy's and St Thomas' NHS Foundation Trust
Collaborator