Development and Validation of HistoMX, a Gene-Expression Platform for Molecular Interpretation of Kidney Allograft Biopsies

NCT07700563 | Completed

• 1 other identifier: HistoMXv3
• Study Type: observational
• Target: 2,410
• Locations: 0 countries
• Sites: N/A

Brief Summary

This retrospective multicentre observational study developed and validated HistoMX, an automated gene-expression-based platform for multidimensional molecular interpretation of kidney allograft biopsies. The study included 2,410 archived post-transplant kidney allograft biopsy samples from adult kidney transplant recipients. Formalin-fixed paraffin-embedded biopsy tissue was profiled using the Banff Human Organ Transplant panel on the NanoString nCounter platform. HistoMX integrates locked preprocessing, quality control, single-sample normalization, diagnostic classification, Banff lesion-level modelling, molecular lesion-severity scores, composite injury indices, immune-cell estimation, pathway-enrichment analysis, and automated clinician-facing reporting. The platform was evaluated against reference histology based on the Banff classification. HistoMX was designed to complement, not replace, conventional histopathology by providing standardized molecular evidence across diagnostic, lesion-level, continuous injury, and biological dimensions of kidney allograft injury.

Conditions

Kidney Transplant; Rejection of Renal Transplant; Antibody Mediated Rejection; BK Virus Nephropathy; T-Cell Mediated Rejection; Chronic Kidney Disease (CKD) Stage 5; Kidney Allograft Injury

Keywords

kidney transplantation; kidney allograft biopsy; allograft rejection; antibody-mediated rejection; T-cell mediated rejection; BK virus Nephropathy; Acute tubular injury; Banff Classification; Molecular diagnostics; transcriptomic; gene expression; B-HOT panel; nCounter; FFPE tissue; machine learning; precision medicine; HistoMX

Outcome Measures

Primary Outcomes (2)

• Discrimination of molecular diagnostic classifiers (AUROC)

  Area under the ROC curve for prediction of each main diagnostic category (antibody-mediated rejection, T cell-mediated rejection, any rejection, BK virus nephropathy, acute tubular injury without rejection, no-active-inflammatory complication) versus the Banff reference histological diagnosis, in internal and external validation cohorts.

  At baseline defined by kidney allograft biopsy (single time-point assessment).

• Calibration of molecular diagnostic classifiers (Brier score, log loss)

  Calibration of predicted diagnostic probabilities for each main diagnostic endpoint, assessed using calibration plots, calibration intercept and slope, Brier score, and log loss, compared with the Banff reference histological diagnosis.

  At baseline defined by kidney allograft biopsy (single time-point assessment).

Secondary Outcomes (6)

• Precision-recall performance (AUPRC) of molecular diagnostic classifiers

  At baseline defined by kidney allograft biopsy (single time-point assessment).

• Discrimination of Banff lesion classifiers (AUROC) for binary lesion.

  At baseline defined by kidney allograft biopsy (single time-point assessment).

• Correlation of continuous molecular lesion-severity scores with histological Banff grades.

  At baseline defined by kidney allograft biopsy (single time-point assessment).

• Performance of composite molecular injury indices (AMR/MVI, TCMR/TI, activity, chronicity).

  At baseline defined by kidney allograft biopsy (single time-point assessment).

• Validation of cell-deconvolution estimates

  At baseline defined by kidney allograft biopsy (single time-point assessment).

Study Arms (4)

Development cohort

Multicenter Development cohort. Retrospective. No intervention.

Alberta cohort

Monocenter External validation cohort. Retrospective. No intervention.

Massachussets General Hospital cohort

Monocenter External validation cohort. Retrospective. No intervention.

Arkana Laboratories cohort

External validation cohort. Retrospective available on NCBI. No extervention.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Post-transplant kidney allograft biopsies from adult recipients submitted for B-HOT transcriptomic profiling across eleven European and North American centers.

You may qualify if:

• Adult kidney transplant recipient, defined as age 18 years or older at transplantation
• Post-transplant kidney allograft biopsy
• Archived FFPE kidney allograft biopsy tissue is available and suitable for transcriptomic profiling
• Biopsy submitted for B-HOT nCounter transcriptomic profiling
• Available Banff reference pathology diagnosis
• Available Banff lesion information required for endpoint definition
• Sample meeting prespecified nCounter assay quality-control criteria

You may not qualify if:

• Recipient age \<18 years at transplantation
• Multi-organ transplantation
• Pre-transplant biopsy
• Missing Banff reference pathology diagnosis
• Failure of prespecified nCounter quality-control criteria
• Missing or insufficient data required to define the relevant reference endpoint

Sponsors & Collaborators

• Paris Translational Research Center for Organ Transplantation: lead
• OrganX: collaborator
• Université Paris Cité: collaborator
• Arkana Labs: collaborator
• Cedars-Sinai Medical Center: collaborator
• University of Alberta: collaborator
• CareDx: collaborator
• Massachusetts General Hospital: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

Archived formalin-fixed paraffin-embedded post-transplant kidney allograft biopsy tissue and RNA extracted from FFPE tissue for B-HOT nCounter gene-expression profiling. Samples were collected as part of clinical biopsy practice and analysed retrospectively under approved institutional governance.

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: June 24, 2026
• First Posted: July 14, 2026
• Study Start: January 1, 2004
• Primary Completion: May 15, 2026
• Study Completion: May 15, 2026
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share