Clinical trial NCT01893710: International (Pediatric) Peritoneal Biobank
Official title: International (Pediatric) Peritoneal Biobank
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Kidney Failure, Chronic
Peritoneal Dialysis Complication
Transplantation
Healthy
Keywords: peritoneal dialysis
parietal peritoneum
omentum
chronic kidney disease
vasculopathy
Lead sponsor: Heidelberg University
Sponsor class: OTHER
First posted: 2013-07-09
Enrollment: 500
Sex: ALL
Minimum age (years): 1
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: See eligibility data

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.

Detailed description: Please see study protocol and

http://www.pedpd.org

Eligibility criteria: 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

Primary outcomes:
measure: Peritoneal vasculopathy (lumen vessel ratio)
timeFrame: Two years (Mean PD treatment time)
Secondary outcomes:
measure: Number of vessels per peritoneal membrane area (per mm²)
timeFrame: at time of catheter insertion, intercurrent abdominal surgery and at time of renal transplantation
Other outcomes:
measure: Submesothelial thickness (µm)
timeFrame: 2 years (average PD duration)
measure: Submesothelial lymphocyte, macrophage, MMT cell count
timeFrame: 2 years (mean PD duration)
measure: Peritoneal VEGF and pSMAD abundance
timeFrame: 2 years (mean PD duration)
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Narberth
country: United States
facility: The Children´s Hospital of Philadelphia
state: Pennsylvania
city: Vienna
country: Austria
facility: Department of Pediatrics, Medical University Vienna
city: Ghent
country: Belgium
facility: UZ Ghent
city: Prague
country: Czechia
facility: University Children's Hospital
city: Lyon
country: France
facility: Service de Néphrologie Pédiatrique, Hôpital Femme Mere Enfant
city: Strasbourg
country: France
facility: University Children's Hospital
city: Heidelberg
country: Germany
facility: Department of Medicine I (Nephrology), University of Heidelberg
state: BW
city: Berlin
country: Germany
facility: University Children's Hospital
city: Cologne
country: Germany
facility: University Children's Hospital
city: Essen
country: Germany
facility: University Children's Hospital
city: Hamburg
country: Germany
facility: UKE, University Children´s Hospital
city: Marburg
country: Germany
facility: KfH Pediatric Kidney Center, Department of Pediatric Nephrology, University of Marburg
city: Budapest
country: Hungary
facility: University Children's Hospital
city: Genova
country: Italy
facility: University Children'Hospital
city: Milano
country: Italy
facility: University Children's Hospital
city: Padova
country: Italy
facility: Pediatric Nephrology, Dialysis and Transplant Unit
city: Vilnius
country: Lithuania
facility: University children's Hospital
city: Kuala Lumpur
country: Malaysia
facility: Paediatric CAPD unit, Kuala Lumpur Hospital
city: Krakow
country: Poland
facility: Krakow, Jagiellonian University Medical College
city: Barcelona
country: Spain
facility: Hospital Universitario Materno-Infantil Vall d' Hebron
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Bern
country: Switzerland
facility: Children's Hospital, Inselspital, Bern University Hospital and University of Bern
city: Adana
country: Turkey
facility: University Children's Hospital
city: Istanbul
country: Turkey
facility: Cerrahpasa School of Medicine
Study officials:
affiliation: University of Heidelberg, Center for Pediatric and Adolescent Medicine
name: Claus P Schmitt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.