International (Pediatric) Peritoneal Biobank

Study Overview
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Brief Summary
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Within few years the peritoneal membrane of adult peritoneal dialysis (PD) patients undergoes substantial morphological transformation, including progressive fibrosis, vasculopathy and neoangiogenesis. Ultrafiltration capacity steadily declines and ultimately results in PD failure. In children, peritoneal biopsies demonstrating PD associated alterations have not yet been obtained. They, however, should be particularly informative, since secondary tissue and vascular pathology related to ageing or diabetes is absent. An international, prospective peritoneal membrane biopsy study in children on PD will therefore be performed. Biopsies will be obtained at time of PD catheter insertion, on occasion of intercurrent abdominal surgery (e.g. hernia repair, catheter exchange) and at time of renal transplantation. Quantitative histomorphometry and tissue protein expression analyses will be correlated with time integrated PD treatment modalities and functional characteristics as well as inflammatory and cardiovascular comorbidity surrogate parameter. Blood will be obtained during clinical routine sampling. Biopsies will be obtained during clinically indicated operations, without substantially increasing operation time and associated surgical risks. The detailed histomorphometry of the PD membrane will give additional information, potentially impacting on the individual PD regime. 3/2018: The analyses of the pediatric PD biopsy demonstrated early and major transformation of the peritoneal membrane with neutral pH low GDP fluids, and significant vasculopathy already in children with CKD stage 5, further progressing with PD. The underlying mechanisms are partly understood, only. In view of these major findings and the numerous open questions, collection of biosamples will be continued in children and also in adult PD patients. The following questions will be addressed: Molecular counterparts of peritoneal semi-permeability, solute and water transport (beyond AQP1), pathomechanisms and molecular and functional impact of peritoneal transformation with low and high GDP fluids, and the respective pathomechanisms and molecular and functional impact of vascular disease in CKD and with different PD fluids. The impact of renal transplantation following PD will be assessed in a subgroup of patients with tenckhoff catheter removal several weeks after transplantation and a functioning graft.

Detailed Description
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Please see study protocol and http://www.pedpd.org

Official Title
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International (Pediatric) Peritoneal Biobank

Conditions
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Kidney Failure, Chronic, Peritoneal Dialysis Complication, Transplantation, Healthy

Intervention / Treatment
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* Procedure: biopsy sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age 0 to 90 years CKD 5D, peritoneal dialysis and Patients with normal renal function and elective abdominal surgery due to limited abdominal pathology (such as hernia repair, gallstones….) Patients post PD and post Tx Oral and written consent Ability to consent of the adult patient and of the parents and legal guardian of patients not yet of legal age, respectively Exclusion Criteria: Abdominal adhesions, malformation and inflammation beyond PD induced changes Patients with disseminated tumour disease Patients with critical heart failure and other medical conditions, where the additional procedure may confer an increased increase risk Pregnancy Preterm babies (below 37 weeks of gestational age) Serum hemoglobin < 10 g/dl in newborns and < 8 g/dl in children and adults

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br>'Biopsy sampling': Peritoneal biopsies without kidney disease, i.e. diseases not related to the kidney and not affecting the peritoneum. This group is accomplished. | |
| chronic kidney disease<br>Samples will obtained from patients with chronic kidney disease stage 5 (at time of catheter Insertion) | Procedure: biopsy sampling<br>* Two parietal peritoneal samples, each 1 cm² x 0.3 cm in depth and three omental tissue samples, each 1 cm² in size will be obtained. Biopsy sampling will be performed in all groups. This is an observational not an interventional trial.<br>|
| Peritoneal dialysis<br>Patients on PD with different PD fluids and intercurrent abdominal surgery and at time of renal transplantation. | Procedure: biopsy sampling<br>* Two parietal peritoneal samples, each 1 cm² x 0.3 cm in depth and three omental tissue samples, each 1 cm² in size will be obtained. Biopsy sampling will be performed in all groups. This is an observational not an interventional trial.<br>|
| Post PD and with functioning graft<br>Samples will also be collected and analysed from patients with renal transplantation after PD at time of and tenckhoff catheter removal several weeks after Tx or other intercurrent abdominal surgery. | Procedure: biopsy sampling<br>* Two parietal peritoneal samples, each 1 cm² x 0.3 cm in depth and three omental tissue samples, each 1 cm² in size will be obtained. Biopsy sampling will be performed in all groups. This is an observational not an interventional trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peritoneal vasculopathy (lumen vessel ratio) | Digital quantification of degree of vasculopathy, i.e the lumen vessel ratio. Healthy children have a L/V ratio of about 0.7. lower values represent vasculopathy with lumen narrowing, 0 is complete obliteration of the vessel. This measurements will be accompanied by molecular analysis of pathomechanisms (including omics Technology) | Two years (Mean PD treatment time) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of vessels per peritoneal membrane area (per mm²) | Digital histomorphometry of small vessel density per mm² submesothelial section area analysed. | at time of catheter insertion, intercurrent abdominal surgery and at time of renal transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peritoneal dialysis, parietal peritoneum, omentum, chronic kidney disease, vasculopathy