Uraemic Toxins in Chronic Kidney Disease Paediatric Patients: Observational Study

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 At this visit, a blood sample for uraemic toxin concentration is withdrawn and several co-morbidities (growth, protein-energy wasting, cardiovascular disease, quality of life, psychosocial functioning, sleep, attention and executive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 Baseline visit: * Verify inclusion/exclusion criteria. * Obtain and record general patient information: age, sex, medical history, underlying kidney disease, medication history, current medication chart, dialysis settings and demographic information * Assessment of dietary assessment by a skilled dietician by means of 3-day diet diary or three 24-hours recall * Perform clinical assessment including anthropometric parameters and office blood pressure * Perform a body composition monitoring (BCM) in children \> 10 kg * Collection of blood sample (all groups; EDTA immediately on ice; serum 15-30 minutes rest and subsequently on ice), 24 hours urine sample (group 2; 24 hours prior to visit), intradialytic urine sample (group 3) and 24 hours dialysate collection (group 2; 24 hours prior to visit) for determination of uraemic toxin concentration Intermediate visits: * Obtain general patient information: medication chart, changes in medical situation and dialysis settings * Assessment of dietary intake by a skilled dietician by means of 3-day diet diary or three 24-hours recall every 3 months * Perform clinical assessment including anthropometric parameters and office blood pressure * Perform BCM 3-monthly in children \> 10 kg with renal replacement therapy (group 2 and 3) and 1-yearly in children \> 10 kg without renal replacement therapy (group 1) * Collection of blood sample (group 1 to 3; EDTA immediately on ice; serum 15-30 minutes rest and subsequently on ice), 24 hours urine sample (group 2 and 3; 24 hours prior to visit) and 24 hours dialysate collection (group 2; 24 hours prior to visit) every 3 months for determination of uraemic toxin concentration. * Collection of stool sample for determination of microbiota and metabolome 1-yearly (only participants of Ghent University Hospital) * Collection of nails for determination of carbamylation process every 6 months (only participants of Ghent University Hospital) * Perform echocardiography by a skilled paediatric cardiologist every year (visit 2, 5) * Withdraw questionnaires from the parent and/or child assessing quality of life, attention, sleep, executive function and parental functioning every 6 months (visit 2, 4, 6, 8) * Perform 24 hours ambulatory blood pressure measurement in children \> 6 years once a year (visit 2, 5) Final Study Visit: * Obtain general patient information: medication chart, changes in medical situation and dialysis settings (detailed overview appendix 2) * Assessment of dietary assessment by a skilled dietician by means of 3-day diet diary or three 24-hours recall * Perform clinical assessment including anthropometric parameters and office blood pressure * Perform a body composition monitoring (BCM) in children \> 10 kg * Collection of blood sample (group 1 to 3; EDTA immediately on ice; serum 15-30 minutes rest and subsequently on ice), 24 hours urine sample (group 2 and 3; 24 hours prior to visit) and 24 hours dialysate collection (group 2; 24 hours prior to visit) for determination of uraemic toxin concentration * Perform echocardiography by a skilled paediatric cardiologist * Perform 24 hours ambulatory blood pressure measurement in children \> 6 years The following socio-demographic questionnaires are asked to be completed: 1. Assessment of quality of life (QoL) * PedsQL for children (5-18 years) * PedsQL for children, disease specific (8-12 years, 13-18 years) * Parent Proxy Report by parents (2-4 years, 5-7 years, 8-12 years, 13-18 years) * Parent Proxy Report, disease specific by parents (8-12 years, 13-18 years) 2. Assessment of psychological wellbeing * YSR for children (\> 11 years) * CBCL/TRF by parent/teachers (1,5-5 years, 6-18 years) * CBSK for children (8-12 years), CBSA for children (13-18 years) 3. Assessment of attention \& executive functions * DBDRS by parents, teachers (6-16 years) * BRIEF by parents/teachers (5-18 years) 4. Assessment of sleep * ESS questionnaire by parents * CSHQ questionnaire by parents 5. Assessment of family functioning * PIP by parents * HADS by parents * PSI-S by parents * PPS by parents * CVS by parents