Molecular Transcriptomics in Diagnosing Pediatric Kidney Transplant Rejection: the PANDA-Kids-ATLAS Study

NCT07091214 | Not Yet Recruiting

• 1 other identifier: Transcriptomics_PED_001
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Children with kidney failure have markedly increased mortality and face repeated transplantation over their lifetime due to limited allograft half-life (12-15 years). Current biopsy-based diagnoses of rejection (using Banff 2022 criteria) suffer from variability and limited sensitivity. PANDA-Kids-ATLAS will analyze up to 600 pediatric FFPE kidney biopsies across multiple centres using the Banff Human Organ Transplant (B-HOT) NanoString panel to develop and validate molecular classifiers of AMR, TCMR and related phenotypes. A secure REDCap database will integrate molecular, pathological and clinical data, aiming to improve early detection, personalize therapy, and enhance long-term graft survival and patient quality of life.

Conditions

Kidney Rejection Transplant

Keywords

transcriptomics; pediatric kidney transplantation; allograft rejection; precision diagnosis; molecular classifiers

Outcome Measures

Primary Outcomes (1)

• Identification of Molecular Classifiers for Kidney Allograft Rejection Using Banff Human Organ Transplant (B-HOT) Gene Panel via NanoString nCounter®

  Molecular signatures (molecular classifiers) will be identified through bulk transcriptomic analysis utilizing the validated Banff Human Organ Transplant (B-HOT) gene panel, consisting of 770 rejection- and tolerance-related genes. Formalin-fixed, paraffin-embedded (FFPE) biopsy samples from pediatric kidney transplant recipients will be processed and analyzed using the NanoString nCounter® platform. Specifically, molecular classifiers distinguishing classical antibody-mediated rejection (AMR), T-cell mediated rejection (TCMR), and novel Banff 2022 antibody-mediated rejection-related categories-including microvascular inflammation with donor-specific antibodies and negative C4d staining (MVI+DSA-C4d-) and probable antibody-mediated rejection (pABMR)-will be quantified and reported. Classifier results will be summarized as normalized gene expression profiles, enabling clear discrimination among different categories of rejection and non-rejection biopsies.

  3 years

Secondary Outcomes (2)

• Integration of Molecular Classifiers with Clinical Parameters into an Archetype-based Diagnostic System for Kidney Allograft Rejection

  3 years

• Integration of Molecular Classifiers with Biological and Immunological Parameters into an Archetype-based Diagnostic System for Kidney Allograft Rejection

  3 years

Other Outcomes (1)

• Correlation of Archetype-based Diagnostic Profiles with Kidney Allograft Clinical Outcomes

  3 years

Study Arms (4)

Group 1: Classic rejection profile

Active/chronic AMR or TCMR

Group 2: Other rejection profiles

Probable AMR, MVI+DSA- C4d-, borderline or mixed rejection

Group 3: Other diagnoses

CMV, CNI toxicity, recurrence, BK nephropathy

Group 4: Normal biopsies

No lesions (normal biopsy results)

Eligibility Criteria

• Age: 0 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Pediatric kidney transplant recipients

You may qualify if:

• Age ≤ 21 years
• Single kidney transplant recipients (deceased or living donor)
• Written informed consent from patients/guardians

You may not qualify if:

• Multi-organ transplantation history
• Biopsies with insufficient tissue

Sponsors & Collaborators

• Paris Translational Research Center for Organ Transplantation: lead
• Paris Cardiovascular Research Center (Inserm U970): collaborator

Study Sites (1)

Paris Institute for Transplantation and Organ Regeneration (PITOR)

Paris, 75015, France

Location

Related Publications (5)

• Sablik M, Sannier A, Raynaud M, Goutaudier V, Divard G, Astor BC, Weng P, Smith J, Garro R, Warady BA, Zahr RS, Twombley K, Dharnidharka VR, Dandamudi RS, Fila M, Huang E, Sellier-Leclerc AL, Tonshoff B, Rabant M, Verine J, Del Bello A, Berney T, Boyer O, Catar RA, Danger R, Giral M, Yoo D, Girardin FR, Alsadi A, Gourraud PA, Morelon E, Le Quintrec M, Try M, Villard J, Zhong W, Bestard O, Budde K, Chauveau B, Couzi L, Brouard S, Hogan J, Legendre C, Anglicheau D, Aubert O, Kamar N, Lefaucheur C, Loupy A. Microvascular Inflammation of Kidney Allografts and Clinical Outcomes. N Engl J Med. 2025 Feb 20;392(8):763-776. doi: 10.1056/NEJMoa2408835. Epub 2024 Oct 24.

  PMID: 39450752 BACKGROUND

• Halloran PF, Madill-Thomsen KS, Bohmig G, Bromberg J, Budde K, Barner M, Mackova M, Chang J, Einecke G, Eskandary F, Gupta G, Myslak M, Viklicky O, Akalin E, Alhamad T, Anand S, Arnol M, Baliga R, Banasik M, Bingaman A, Blosser CD, Brennan D, Chamienia A, Chow K, Ciszek M, de Freitas D, Deborska-Materkowska D, Debska-Slizien A, Djamali A, Domanski L, Durlik M, Fatica R, Francis I, Fryc J, Gill J, Gill J, Glyda M, Gourishankar S, Grenda R, Gryczman M, Hruba P, Hughes P, Jittirat A, Jurekovic Z, Kamal L, Kamel M, Kant S, Kasiske B, Kojc N, Konopa J, Lan J, Mannon R, Matas A, Mazurkiewicz J, Miglinas M, Muller T, Narins S, Naumnik B, Patel A, Perkowska-Ptasinska A, Picton M, Piecha G, Poggio E, Bloudickova SR, Samaniego-Picota M, Schachtner T, Shin S, Shojai S, Sikosana MLN, Slatinska J, Smykal-Jankowiak K, Solanki A, Veceric Haler Z, Vucur K, Weir MR, Wiecek A, Wlodarczyk Z, Yang H, Zaky Z. Subthreshold rejection activity in many kidney transplants currently classified as having no rejection. Am J Transplant. 2025 Jan;25(1):72-87. doi: 10.1016/j.ajt.2024.07.034. Epub 2024 Aug 6.

  PMID: 39117038 BACKGROUND

• Mengel M, Loupy A, Haas M, Roufosse C, Naesens M, Akalin E, Clahsen-van Groningen MC, Dagobert J, Demetris AJ, Duong van Huyen JP, Gueguen J, Issa F, Robin B, Rosales I, Von der Thusen JH, Sanchez-Fueyo A, Smith RN, Wood K, Adam B, Colvin RB. Banff 2019 Meeting Report: Molecular diagnostics in solid organ transplantation-Consensus for the Banff Human Organ Transplant (B-HOT) gene panel and open source multicenter validation. Am J Transplant. 2020 Sep;20(9):2305-2317. doi: 10.1111/ajt.16059. Epub 2020 Jun 27.

  PMID: 32428337 BACKGROUND

• Zielinski D, Goutaudier V, Sablik M, Divard G, Aubert O, Piedrafita A, Mezine F, Dagobert J, Certain A, Robin B, Gueguen J, Rabant M, Duong van Huyen JP, Sannier A, Randoux-Lebrun C, Maanaoui M, Lionet A, Gibier JB, Gnemmi V, Le Quintrec M, Chauveau B, Vermorel A, Couzi L, Bestard O, Elias M, Louis K, Rosales IA, Smith RN, Kung VL, Anglicheau D, Legendre C, Del Bello A, Huang E, Adam B, Kamar N, Colvin RB, Mengel M, Lefaucheur C, Loupy A. Molecular diagnosis of kidney allograft rejection based on the Banff Human Organ Transplant gene panel: A multicenter international study. Am J Transplant. 2025 Aug;25(8):1631-1642. doi: 10.1016/j.ajt.2025.04.025. Epub 2025 May 8.

  PMID: 40345499 BACKGROUND

• Fichtner A, Gauche L, Susal C, Tran TH, Waldherr R, Krupka K, Guzzo I, Carraro A, Oh J, Zirngibl M, Weitz M, Konig J, Buscher A, Berta L, Simon T, Awan A, Rusai K, Topaloglu R, Peruzzi L, Printza N, Kim JJ, Weber LT, Melk A, Pape L, Rieger S, Patry C, Hocker B, Tonshoff B; CERTAIN study group. Incidence, risk factors, management strategies, and outcomes of antibody-mediated rejection in pediatric kidney transplant recipients-a multicenter analysis of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN). Pediatr Nephrol. 2025 Feb;40(2):491-503. doi: 10.1007/s00467-024-06487-2. Epub 2024 Sep 16.

  PMID: 39283519 BACKGROUND

Related Links

• CERTAIN registry protocol for participating centers via CERTAIN

Study Officials

• Evgenia Preka, MD, PhDc

  INSERM U970

  PRINCIPAL INVESTIGATOR

• Alexandre Loupy, MD, PhD

  INSERM U970

  STUDY CHAIR

• Valentin Goutaudier, MD, PhD

  INSERM U970

  STUDY CHAIR

Central Study Contacts

Evgenia Preka, MD, PhDc

CONTACT

+33 1 44 23 60 00; evgenia.preka@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2025
• First Posted: July 29, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: after the completion and publication of the study
• Access Criteria: Participating centres' PI can contact the PI of the study for access in their center's results.

Locations

FR (1)