Uraemic Toxins in Chronic Kidney Disease Paediatric Patients: Interventional Study (UToPaed_3)

Part 3 of: 'Conceptualisation and Validation of a Paradigm Based on Uraemic Toxins for Management of Chronic Kidney Disease in Paediatric Patients (UToPaed)'

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 UToPaed (part 1), 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). Those toxins of which concentrations are best correlated with comorbidities during the progress of CKD and those having representative kinetics (UToPaed - part 2: Kinetic analysis) will be selected as markers. During this third part of UToPaed, these markers will be, together with the comorbidities, further tracked after interventions, i.e. starting on dialysis, transplantation, changes in dialysis strategy.

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).

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Other: Change in treatment strategy

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium
    • Ghent University Hospital - Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Subject 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.

Subject Exclusion Criteria:

• N.A.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CKD - no dialysis; Change in treatment strategy: Start on dialysis, transplantation	Other: Change in treatment strategy; Start on dialysis, transplantation, change of PD prescription, change of HD prescription
Experimental: Patients on PD; Change in treatment strategy: Change of PD prescription, start on HD, transplantation	Other: Change in treatment strategy; Start on dialysis, transplantation, change of PD prescription, change of HD prescription
Experimental: Patients on HD; Change in treatment strategy: Change of HD prescription, transplantation	Other: Change in treatment strategy; Start on dialysis, transplantation, change of PD prescription, change of HD prescription

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of concentrations of uraemic toxins as measured in HD patients after interventions with those as will be predicted by the kinetic model (model validation)	up to 4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Decrease of blood concentrations of uraemic toxins in PD and HD patients by changing dialysis prescription to the optimal dialysis strategy	up to 4 years

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Agentschap voor Innovatie door Wetenschap en Technologie; University Ghent
• Investigators: Principal Investigator: Sunny Eloot, Prof Dr, Ghent University Hospital - Nephrology; Study Chair: Johan Vande Walle, Prof Dr, Ghent University Hospital - Paediatric Nephrology; Study Chair: Ann Raes, Prof Dr, Ghent University Hospital - Paediatric Nephrology; Study Chair: Wim Van Biesen, Prof Dr, Ghent University Hospital - Nephrology; Study Chair: Evelien Snauwaert, Ghent University Hospital - Paediatric Nephrology

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: December 1, 2015
• First Submitted That Met QC Criteria: December 16, 2015
• First Posted (Estimate): December 18, 2015

Study Record Updates

• Last Update Posted (Actual): August 16, 2021
• Last Update Submitted That Met QC Criteria: August 9, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Pediatrics; Dialysis; Nephrology
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: UGent_UToPaed_3