Uraemic Toxins in Chronic Kidney Disease Paediatric Patients: Interventional Study

This is an interventional multicenter study in children (≤ 18 years) with chronic kidney disease (CKD) stage 2 to 5D with or without renal replacement therapy. They will be followed for a total duration of 24 months. Concentrations of the uraemic toxin markers and the different comorbidities will be followed after an intervention. Some interventions will just happen in the treatment of the CKD child: e.g. transplantation, start on dialysis, needed switch from PD to HD. In the patients on PD, different approaches will be followed: more frequent exchanges overnight, PET-directed dialysis regimes, adapted PD, using a mix of short, small volume dwells, with longer, high volume dwells. These different strategies have so far only been tested using the classic adequacy parameters urea and creatinine. The intervention is that the children, as included in the longitudinal study, will be studied while on at least two different PD strategies, serving as their own control, whereby the strategy will be linked with the concentration of the uraemic toxin markers and comorbidities. In the patients on HD, different dialysis strategies will be studied: conventional haemodialysis 3x/week, daily haemodialysis, haemodiafiltration 3x/week, nocturnal 8h dialysis 3x/week, and the optimal dialysis regime as derived from the kinetic analysis (UToPaed\_2). The intervention is that the children, as included in the longitudinal study, will be studied with at least 2 of the strategies, and that differences in plasma concentrations and removal rate of the uraemic toxin markers will be measured. The measured predialysis concentrations, time averaged concentrations (TACs), and total solute removal with the different strategies will be compared to the results of the kinetic simulations in order to validate the calibrated kinetic models of the uraemic toxin markers. Based on the results, guidance on the most optimal dialysis strategy for each child will be developed, and the child will consequently be treated on that modality during 1 year, to allow evaluation of the longer term impact on quality of life, catch up growth, study results and emergence of new comorbidities. The therapeutic tool comprises an open access user-friendly prediction simulator, based on the kinetics of the new markers (PAEDSIM) to simulate different dialysis strategies. With different patient characteristics and uraemic toxin concentrations as input for the simulation model, the program will derive the optimal dialysis strategy for the individual patient striving for low predialysis concentrations and TACs. The clinical use of these findings will be promoted by the organisation of a 'CKD Academy' with workshops about the prediction simulator (PAEDSIM) and the related laboratory techniques (see utilisation strategies).