Part 1 of: 'Conceptualisation and Validation of a Paradigm Based on Uraemic Toxins for Management of Chronic Kidney Disease in Paediatric Patients (UToPaed)'
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University Hospital, Ghent
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Detect whether uraemic toxin concentrations are correlated with the different measured co-morbidities
Study Overview
Brief Summary
Children with chronic kidney disease (CKD) suffer from one of the most devastating diseases in childhood resulting in a lifelong need for health care, and a 3 times decreased life expectancy. In addition, they have important comorbidities that negatively impact on their quality of life and integration in society, jeopardizing their future even after a potential transplantation. Retention of uraemic toxins is accepted to play a major role in the pathogenesis of the comorbid conditions, but studies in children are lacking. Furthermore, there are currently no good tools to evaluate severity and monitor adequacy of treatment, resulting in suboptimal management.
The overall scientific objective of this four years UToPaed IWT-TBM project is to provide the clinician with new diagnostic and therapeutic tools for the management of children with CKD, based on the improved understanding of uraemic toxicity.
In this first part of UToPaed, the investigators will associate concentrations of a wide variety of uraemic toxins with different comorbidities in CKD children, i.e. growth, protein-energy wasting, quality of life, cardiovascular risk factors, circadian rhythm, sleep quality, and psychosocial and neurocognitive functioning (i.e. cross-sectional and longitudinal). The toxins of which concentrations are best correlated with comorbidities during the progress of CKD and eventually have representative kinetics (UToPaed - part 2: Kinetic analysis) will be selected as markers. These markers will be, together with the comorbidities, further tracked after interventions, i.e. starting on dialysis, transplantation, changes in dialysis strategy (UToPaed - part 3 - intervention study).
From the validated kinetic models (UToPaed - part 2 and 3), an open access user-friendly prediction simulator (PAEDSIM) based on patient characteristics and marker concentrations will be developed to optimise and individualise the dialysis therapy.
By providing clinicians with more advanced and appropriate tools to improve management of all children with CKD, i.e. better assessment of the degree of renal dysfunction, better determination of the ideal time to start renal replacement therapy, and more accurate monitoring of dialysis adequacy, the investigators aim to improve neurocognitive and psychosocial functioning (short term), growth, maturation into puberty, and social integration (median term) and survival (long term).
Detailed Description
This is a prospective observational multicenter study in children (≤ 18 years) with chronic kidney disease (CKD) stage 2 to 5D with or without renal replacement therapy. In this study, 60 children with CKD stage 2 - 5 (without renal replacement therapy)(GROUP 1), 30 children with CKD stage 5D treated with peritoneal dialysis (GROUP 2) and 30 children with CKD stage 5D treated with haemodialysis (GROUP 3) will be followed for a total duration of 24 months.
The study participants are evaluated on their standard visit at the outpatient clinic every 3 months. At this visit, a blood sample for uraemic toxin concentration is withdrawn and several co-morbidities (growth, protein-energy wasting, cardiovascular disease, quality of life, psychosocial functioning, sleep, attention and executive functions) are assessed. Anthropometric parameters, dietary assessment, stool evaluation, nail evaluation, office and 24 hours ambulatory blood pressure monitoring, echocardiography and questionnaires are used to map out the several co-morbidities.
Blood analyses are performed to get the concentrations of a wide variety of uraemic toxins: i.e. small water soluble solutes, middle molecules and protein-bound solutes. All blood analyses within this project are performed in the Ghent University Hospital: i.e. urea, creatinine, calcium, and phosphorus are determined in the routine laboratory of the Ghent University Hospital using standard methods, while all other uraemic toxins are determined in the laboratory of the Nephrology Section using ELISA and (in-house developed) HPLC/UPLC techniques. For the protein-bound solutes two runs are needed to distinguish between total and free fractions of the protein-bound solutes.
The following actions are performed prior to enrolment:
- Review medical history to determine eligibility based on inclusion/exclusion criteria
- Obtain document consent from participant (>12 years) and parent/representative on study consent form
- Schedule study visits for individuals who are eligible and available for the duration of the study
- Provide potential participants with instructions needed to prepare for first study visit
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- — to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Provide signed and dated informed consent form.
- •Willing to comply with all study procedures and be available for the duration of the study
- •Male or female, aged ≤ 18 years
- •Diagnosed with chronic kidney disease stage 2 to 5D, according to the K/DOQI guidelines.
Exclusion Criteria
- •Partially exclusion of children and/or parents who cannot fill in the questionnaires due to language barriers. They will be excluded only from the questionnaires; the other comorbidities will be followed.
- •Partially exclusion of children who cannot fill in the questionnaires due to mental retardation. They will be excluded only from the questionnaires; the other comorbidities will be followed.
Outcomes
Primary Outcomes
Detect whether uraemic toxin concentrations are correlated with the different measured co-morbidities
Time Frame: 2 years
Secondary Outcomes
No secondary outcomes reported