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| ID | Type | Description | Link |
|---|---|---|---|
| University of Heidelberg | Other Identifier | University of Heidelberg, Medical Faculty |
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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.
Please see study protocol and
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
| |
| Peritoneal dialysis | Patients on PD with different PD fluids and intercurrent abdominal surgery and at time of renal transplantation. |
| |
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| biopsy sampling | Procedure | 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. |
| 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) |
| 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 |
| 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 |
Inclusion Criteria
Exclusion Criteria:
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See eligibility data
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Claus P Schmitt, Prof | Contact | +49 6221 56 | 39313 | claus.peter.schmitt@med.uni-heidelberg.de |
| Name | Affiliation | Role |
|---|---|---|
| Claus P Schmitt, MD | University of Heidelberg, Center for Pediatric and Adolescent Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Active, not recruiting | Birmingham | Alabama | 35233 | United States | |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37833387 | Derived | 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. | |
| 35185912 |
| Label | URL |
|---|---|
| International Pediatric Peritoneal Dialysis Network | View source |
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Parietal ond omental peritoneal membrane specimen will be collected in all groups
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) |
| Children's Mercy Hospital |
| Recruiting |
| Kansas City |
| Missouri |
| 64108 |
| United States |
|
| The Children´s Hospital of Philadelphia | Active, not recruiting | Narberth | Pennsylvania | 19104 | United States |
| Department of Pediatrics, Medical University Vienna | Recruiting | Vienna | 1090 | Austria |
|
| UZ Ghent | Recruiting | Ghent | 9890 | Belgium |
|
| University Children's Hospital | Recruiting | Prague | 15006 | Czechia |
|
| Service de Néphrologie Pédiatrique, Hôpital Femme Mere Enfant | Recruiting | Lyon | 69677 | France |
|
| University Children's Hospital | Recruiting | Strasbourg | 67098 | France |
|
| Department of Medicine I (Nephrology), University of Heidelberg | Recruiting | Heidelberg | Baden-Wurttemberg | 69120 | Germany |
|
| University Children's Hospital | Active, not recruiting | Berlin | 10117 | Germany |
| University Children's Hospital | Recruiting | Cologne | 50931 | Germany |
|
| University Children's Hospital | Recruiting | Essen | 45122 | Germany |
|
| UKE, University Children´s Hospital | Recruiting | Hamburg | 20251 | Germany |
|
| KfH Pediatric Kidney Center, Department of Pediatric Nephrology, University of Marburg | Recruiting | Marburg | 35043 | Germany |
|
| University Children's Hospital | Recruiting | Budapest | 1083 | Hungary |
|
| University Children'Hospital | Active, not recruiting | Genova | 16147 | Italy |
| University Children's Hospital | Recruiting | Milan | 20122 | Italy |
|
| Pediatric Nephrology, Dialysis and Transplant Unit | Active, not recruiting | Padova | 35128 | Italy |
| University children's Hospital | Recruiting | Vilnius | 08406 | Lithuania |
|
| Paediatric CAPD unit, Kuala Lumpur Hospital | Active, not recruiting | Kuala Lumpur | 50586 | Malaysia |
| Krakow, Jagiellonian University Medical College | Recruiting | Krakow | 30663 | Poland |
|
| Hospital Universitario Materno-Infantil Vall d' Hebron | Recruiting | Barcelona | 08035 | Spain |
|
| Karolinska University Hospital | Active, not recruiting | Stockholm | 17176 | Sweden |
| Children's Hospital, Inselspital, Bern University Hospital and University of Bern | Active, not recruiting | Bern | 3010 | Switzerland |
| University Children's Hospital | Recruiting | Adana | 01330 | Turkey (Türkiye) |
|
| Cerrahpasa School of Medicine | Active, not recruiting | Istanbul | 34303 | Turkey (Türkiye) |
| 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. |
| 34233458 | Derived | 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. |
| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| D051436 | Renal Insufficiency, Chronic |
| D014652 | Vascular Diseases |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D015193 | Chorionic Villi Sampling |
| ID | Term |
|---|---|
| D001706 | Biopsy |
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D013048 | Specimen Handling |
| D011296 | Prenatal Diagnosis |
| D003944 | Diagnostic Techniques, Obstetrical and Gynecological |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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