International (Pediatric) Peritoneal Biobank
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age1-90
SponsorHeidelberg University
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
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
Trial population
See eligibility data
Trial design
Design model
Other
Time perspective
Prospective
Treatments tested in this trial
biopsy sampling
Procedure/SurgeryTwo 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.
Treatment groups
500 Participants
are divided into 4 treatment groupsGroup A: Control0 interventions
Group B: chronic kidney disease1 intervention
Group C: Peritoneal dialysis1 intervention
Group D: Post PD and with functioning graft1 intervention
Trial outcomes
Primary outcomes
1
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)
Time frame
Two years (Mean PD treatment time)Secondary outcomes
1
Number of vessels per peritoneal membrane area (per mm²)
Digital histomorphometry of small vessel density per mm² submesothelial section area analysed.
Time frame
at time of catheter insertion, intercurrent abdominal surgery and at time of renal transplantationOther outcomes
1
Submesothelial thickness (µm)
Digital imaging analysis of submesothelial thickness as a marker of peritoneal fibrosis (distance between mesothelium and adjacent muscle/adipos tissue)
Time frame
2 years (average PD duration)2
Submesothelial lymphocyte, macrophage, MMT cell count
Quantification of peritoneal leucocyte Infiltration, i.e. number of CD45 positive lymphocytes and CD68 positive macrophages per mm² of submesothelial section area . The number of cells that underwent mesothelial-mesenchymal transition per mm² submesothelial section are quantified by immunohistochemical co-staining of mesothelial and fibroblast marker (cytokeratin and FSP1).
Time frame
2 years (mean PD duration)3
Peritoneal VEGF and pSMAD abundance
Key cytokines involved in peritoneal membrane transformation will be measured immunohistochemically. These are VEGF and TGF-beta induced p-SMAD (%positive area per section area analysed).
Time frame
2 years (mean PD duration)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov