International (Pediatric) Peritoneal Biobank

Sponsor

Heidelberg University (Other)

Overall Status

Recruiting

CT.gov ID

NCT01893710

Collaborator

(none)

500

Enrollment

Locations

214

Duration (Months)

19.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Failure, Chronic Peritoneal Dialysis Complication Transplantation Healthy	Procedure: biopsy sampling

Detailed Description

Please see study protocol and

http://www.pedpd.org

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

500 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

International (Pediatric) Peritoneal Biobank

Study Start Date :

Feb 1, 2011

Anticipated Primary Completion Date :

Oct 1, 2028

Anticipated Study Completion Date :

Dec 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Control '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 Samples will obtained from patients with chronic kidney disease stage 5 (at time of catheter Insertion)	Procedure: biopsy sampling 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.
Peritoneal dialysis Patients on PD with different PD fluids and intercurrent abdominal surgery and at time of renal transplantation.	Procedure: biopsy sampling 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.
Post PD and with functioning graft 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 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.

Outcome Measures

Primary Outcome Measures

Peritoneal vasculopathy (lumen vessel ratio) [Two years (Mean PD treatment time)]
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)

Secondary Outcome Measures

Number of vessels per peritoneal membrane area (per mm²) [at time of catheter insertion, intercurrent abdominal surgery and at time of renal transplantation]
Digital histomorphometry of small vessel density per mm² submesothelial section area analysed.

Other Outcome Measures

Submesothelial thickness (µm) [2 years (average PD duration)]
Digital imaging analysis of submesothelial thickness as a marker of peritoneal fibrosis (distance between mesothelium and adjacent muscle/adipos tissue)
Submesothelial lymphocyte, macrophage, MMT cell count [2 years (mean PD duration)]
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).
Peritoneal VEGF and pSMAD abundance [2 years (mean PD duration)]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
3	The Children´s Hospital of Philadelphia	Narberth	Pennsylvania	United States	19104
4	Department of Pediatrics, Medical University Vienna	Vienna		Austria	1090
5	UZ Ghent	Ghent		Belgium	9890
6	University Children's Hospital	Prague		Czechia	15006
7	Service de Néphrologie Pédiatrique, Hôpital Femme Mere Enfant	Lyon		France	69677
8	University Children's Hospital	Strasbourg		France	67098
9	Department of Medicine I (Nephrology), University of Heidelberg	Heidelberg	BW	Germany	69120
10	University Children's Hospital	Berlin		Germany	10117
11	University Children's Hospital	Cologne		Germany	50931
12	University Children's Hospital	Essen		Germany	45122
13	UKE, University Children´s Hospital	Hamburg		Germany	20251
14	KfH Pediatric Kidney Center, Department of Pediatric Nephrology, University of Marburg	Marburg		Germany	35043
15	University Children's Hospital	Budapest		Hungary	1083
16	University Children'Hospital	Genova		Italy	16147
17	University Children's Hospital	Milano		Italy	20122
18	Pediatric Nephrology, Dialysis and Transplant Unit	Padova		Italy	35128
19	University children's Hospital	Vilnius		Lithuania	08406
20	Paediatric CAPD unit, Kuala Lumpur Hospital	Kuala Lumpur		Malaysia	50586
21	Krakow, Jagiellonian University Medical College	Krakow		Poland	30663
22	Hospital Universitario Materno-Infantil Vall d' Hebron	Barcelona		Spain	08035
23	Karolinska University Hospital	Stockholm		Sweden	17176
24	Children's Hospital, Inselspital, Bern University Hospital and University of Bern	Bern		Switzerland	3010
25	University Children's Hospital	Adana		Turkey	01330
26	Cerrahpasa School of Medicine	Istanbul		Turkey	34303