International (Pediatric) Peritoneal Biobank

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Kidney Failure, Chronic; Transplantation; Peritoneal Dialysis Complication
• Intervention / Treatment: Procedure: biopsy sampling

Detailed Description

Please see study protocol and

http://www.pedpd.org

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Claus P Schmitt, Prof; Phone Number: 39313 +49 6221 56; Email: claus.peter.schmitt@med.uni-heidelberg.de

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Department of Pediatrics, Medical University Vienna
    • Contact: Klaus Arbeiter, MD; Phone Number: +43 1404003257; Email: klaus.arbeiter@meduniwien.ac.at
    • Principal Investigator: Klaus Arbeiter, MD
• Belgium
  • Ghent, Belgium, 9890
    • Recruiting
    • UZ Ghent
    • Contact: Johan Van de Walle, MD; Phone Number: +32 93322483; Email: Johan.VandeWalle@uzgent.be
    • Principal Investigator: Johan Van de Walle, MD
• Czechia
  • Prague, Czechia, 15006
    • Recruiting
    • University Children's Hospital
    • Contact: Karel Vondrak, MD; Phone Number: +42 0224432078; Email: 8080@seznam.cz
    • Principal Investigator: Karel Vondrak, MD
• France
  • Lyon, France, 69677
    • Recruiting
    • Service de Néphrologie Pédiatrique, Hôpital Femme Mere Enfant
    • Contact: Bruno Ranchin, MD; Phone Number: +33 427856129; Email: bruno.ranchin@chu-lyon.fr
    • Principal Investigator: Bruno Ranchin, MD
  • Strasbourg, France, 67098
    • Recruiting
    • University Children's Hospital
    • Contact: Ariane Zaloszyc, MD; Phone Number: +333388127742; Email: ariane.zaloszyc@chru-strasbourg.fr
    • Principal Investigator: Ariane Zaloszyc, MD
• Germany
  • Berlin, Germany, 10117
    • Active, not recruiting
    • University Children's Hospital
  • Cologne, Germany, 50931
    • Recruiting
    • University Children's Hospital
    • Contact: Christina Taylan, MD; Phone Number: +49 2214784391; Email: christina.taylan@uk-koeln.de
    • Principal Investigator: Christina Taylan, MD
  • Essen, Germany, 45122
    • Recruiting
    • University Children's Hospital
    • Contact: Rainer Büscher, MD; Phone Number: +49 201 723-2738; Email: Rainer.Buescher@uk-essen.de
    • Principal Investigator: Rainer Büscher, MD
  • Hamburg, Germany, 20251
    • Recruiting
    • UKE, University Children´s Hospital
    • Contact: Jun Oh, MD; Phone Number: +49 40 7410 0; Email: j.oh@uke.de
    • Sub-Investigator: Christian Brix, MD
  • Marburg, Germany, 35043
    • Recruiting
    • KfH Pediatric Kidney Center, Department of Pediatric Nephrology, University of Marburg
    • Contact: Günter Klaus, Prof; Phone Number: +49 64215862254; Email: Guenter.Klaus@kfh-dialyse.de
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Recruiting
      • Department of Medicine I (Nephrology), University of Heidelberg
      • Contact: Katrin Klein, MD; Phone Number: +49 62215639776; Email: katrin.klein@med.uni-heidelberg.de
• Hungary
  • Budapest, Hungary, 1083
    • Recruiting
    • University Children's Hospital
    • Contact: Peter Sallay, MD; Phone Number: +36 13343186; Email: sallay.peter@med.semmelweis-univ.hu
    • Principal Investigator: Peter Sallay, MD
• Italy
  • Genova, Italy, 16147
    • Active, not recruiting
    • University Children'Hospital
  • Milan, Italy, 20122
    • Recruiting
    • University Children's Hospital
    • Contact: Sara Testa, MD; Phone Number: +39 0257992471; Email: saratesta@tiscali.it
    • Principal Investigator: Sara Testa, MD
  • Padova, Italy, 35128
    • Active, not recruiting
    • Pediatric Nephrology, Dialysis and Transplant Unit
• Lithuania
  • Vilnius, Lithuania, 08406
    • Recruiting
    • University Children's Hospital
    • Contact: Rimante Cerkauskiene, MD; Phone Number: +37 052720427; Email: rimantec@yahoo.com
    • Principal Investigator: Rimante Cerkauskiene, MD
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Active, not recruiting
    • Paediatric CAPD unit, Kuala Lumpur Hospital
• Poland
  • Krakow, Poland, 30663
    • Recruiting
    • Krakow, Jagiellonian University Medical College
    • Contact: Dorota Drozdz, MD; Phone Number: +48 12 658 11 59; Email: dadrozdz@cm-uj.krakow.pl
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Materno-Infantil Vall d' Hebron
    • Contact: Gema Ariceta, MD; Phone Number: +34 934893082; Email: gariceta@vhebron.net
    • Principal Investigator: Gema Ariceta, MD
• Sweden
  • Stockholm, Sweden, 17176
    • Active, not recruiting
    • Karolinska University Hospital
• Switzerland
  • Bern, Switzerland, 3010
    • Active, not recruiting
    • Children's Hospital, Inselspital, Bern University Hospital and University of Bern
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01330
    • Recruiting
    • University Children's Hospital
    • Contact: Aysun K Bayazit, MD; Phone Number: +90 3223386935; Email: ayskar@cu.edu.tr
    • Principal Investigator: Aysun K Bayazit, MD
  • Istanbul, Turkey (Türkiye), 34303
    • Active, not recruiting
    • Cerrahpasa School of Medicine
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Active, not recruiting
      • University of Alabama at Birmingham
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Recruiting
      • Children's Mercy Hospital
      • Principal Investigator: Bradley A. Warady, MD
      • Contact: Bradley A. Warady, MD; Phone Number: +1 8162343010; Email: bwarady@cmh.edu
  • Pennsylvania
    • Narberth, Pennsylvania, United States, 19104
      • Active, not recruiting
      • The Children´s Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

See eligibility data

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Submesothelial thickness (µm)	Digital imaging analysis of submesothelial thickness as a marker of peritoneal fibrosis (distance between mesothelium and adjacent muscle/adipos tissue)	2 years (average PD duration)
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).	2 years (mean PD duration)
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).	2 years (mean PD duration)

Collaborators and Investigators

• Sponsor: Heidelberg University
• Investigators: Principal Investigator: Claus P Schmitt, MD, University of Heidelberg, Center for Pediatric and Adolescent Medicine

Publications and helpful links

General Publications

• Catar RA, Bartosova M, Kawka E, Chen L, Marinovic I, Zhang C, Zhao H, Wu D, Zickler D, Stadnik H, Karczewski M, Kamhieh-Milz J, Jorres A, Moll G, Schmitt CP, Witowski J. Angiogenic Role of Mesothelium-Derived Chemokine CXCL1 During Unfavorable Peritoneal Tissue Remodeling in Patients Receiving Peritoneal Dialysis as Renal Replacement Therapy. Front Immunol. 2022 Feb 4;13:821681. doi: 10.3389/fimmu.2022.821681. eCollection 2022.
• Bartosova M, Zhang C, Schaefer B, Herzog R, Ridinger D, Damgov I, Levai E, Marinovic I, Eckert C, Romero P, Sallay P, Ujszaszi A, Unterwurzacher M, Wagner A, Hildenbrand G, Warady BA, Schaefer F, Zarogiannis SG, Kratochwill K, Schmitt CP. Glucose Derivative Induced Vasculopathy in Children on Chronic Peritoneal Dialysis. Circ Res. 2021 Aug 20;129(5):e102-e118. doi: 10.1161/CIRCRESAHA.121.319310. Epub 2021 Jul 8.
• Levai E, Marinovic I, Bartosova M, Zhang C, Schaefer B, Jenei H, Du Z, Drozdz D, Klaus G, Arbeiter K, Romero P, Schwenger V, Schwab C, Szabo AJ, Zarogiannis SG, Schmitt CP. Human peritoneal tight junction, transporter and channel expression in health and kidney failure, and associated solute transport. Sci Rep. 2023 Oct 13;13(1):17429. doi: 10.1038/s41598-023-44466-z.

Helpful Links

• International Pediatric Peritoneal Dialysis Network

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2011
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 27, 2013
• First Submitted That Met QC Criteria: July 2, 2013
• First Posted (Estimated): July 9, 2013

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: chronic kidney disease; peritoneal dialysis; vasculopathy; omentum; parietal peritoneum
• Additional Relevant MeSH Terms: Urogenital Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Biopsy; Cytodiagnosis; Diagnostic Techniques, Surgical; Diagnostic Techniques, Obstetrical and Gynecological; Prenatal Diagnosis; Chorionic Villi Sampling
• Other Study ID Numbers: IPPB Biobank; University of Heidelberg (Other Identifier: University of Heidelberg, Medical Faculty)