Calcium balance studies in children and young adults
Research type
Research Study
Full title
Assessing calcium balance in children with chronic kidney disease and healthy control
IRAS ID
219269
Contact name
Rukshana Shroff
Contact email
Sponsor organisation
Great Ormond Street Hospital for Children NHS Foundation Trust
Duration of Study in the UK
4 years, 11 months, 31 days
Research summary
Background: Childhood and adolescence are important periods for bone growth. The growing skeleton of children has a high requirement for two important minerals - calcium (Ca) and phosphate – in order to mineralize properly and for the bones to gain maximal strength. In healthy children the Ca content of the skeleton increases from ~25g at birth to ~1200g in adults. Approximately 25% of total skeletal mineralization occurs in adolescence, giving rise to a greatly increased Ca and P requirement. If the bones do not get enough Ca they can become weak and fracture easily even in children who are otherwise healthy.
Patients with chronic kidney disease (CKD) can have weak bones that fracture easily, and also a high risk of dying from heart failure. Bone disease and heart disease are linked, and happen because of changes in the balance between two important minerals in the body - calcium (Ca) and phosphate (P). Ca is removed from the bones, making bones soft, causing bone pain, bone deformities and a high risk of fractures. The growing bones of children are particularly vulnerable. Nearly 90% of children on dialysis (a treatment for severe CKD) have soft bones. Boys and girls with even early stages of CKD are at a 2 – 3 times greater risk of fractures compared to their healthy peers. However, it is also possible that too much Ca can get deposited in other parts of the body, such as the arteries. This can make the arteries thick and hard, which puts extra strain on the heart leading to heart failure.
Why we need this research: The total amount of Ca in the body can be measured by Ca balance. In order to develop this new way of measuring Ca balance, we need to know the normal Ca balance in healthy boys and girls. Ca balance can change in boys and girls at different ages and as they go through puberty, so we need to measure this in children of all ages, and see if it is linked with how much Ca is in the food. Ca balance measurements will be compared with special blood tests for bones.
We can then study the Ca balance in children with bone diseases or kidney problems so that we can give them the correct medicines they need to keep their bones strong. To prevent and treat bone disease, CKD patients are regularly given medicines called phosphate binders (P-binders) and vitamin D. Some P-binders and vitamin D increase Ca intake into the body. So, if a patient has less Ca in their body, this increased Ca goes into their bones and makes them stronger. But, if a patient has too much Ca already, the extra Ca can get dumped in the arteries. This means that the very medicines used to treat children may be causing them serious long-term harm. To prescribe medicines correctly, it is important that we know how their Ca balance.
A new test for Ca balance: We will use a new method to measure Ca balance that looks at the proportion of different natural forms of Ca (called isotopes; isotopes are different forms of the same atom) in the body. Natural Ca isotopes are found in food and taken up in the bones or passed out in urine and stool in fixed proportions. By measuring the proportion of different Ca isotopes in food, blood, urine and stool we can calculate if there is too much or too little Ca in the body.
Research goals:
In order to develop this new way of measuring Ca balance which could be used in day- to-day care, we will measure Ca balance in children with CKD and on dialysis and compare the results with healthy boys and girls of the same age. Ca balance measurements will also be compared with two different x-ray measurements of bone density (by peripheral quantitative CT scan (pQCT) and dual energy x-ray absorptiometry (DEXA)) and special blood tests for bones.Benefits of our research:
By measuring the Ca balance of children with CKD using a carefully developed technique, we can determine if a child has too little Ca for their bones (and therefore needs medications that provide more Ca), just the right amount, or too much (in which case Ca containing medicines can be harmful).
Our group of young people with kidney disease has urged us to perform this study as it focuses on outcomes that matter most to them: long-term bone and heart health.REC name
London - City & East Research Ethics Committee
REC reference
17/LO/0007
Date of REC Opinion
14 Feb 2017
REC opinion
Further Information Favourable Opinion