Urinary Proteomics in Predicting Heart Transplantation Outcomes (uPROPHET)-Rationale and database description

Area of Science:

• Biochemistry
• Immunology
• Transplantation Science

Background:

• Heart transplantation (HTx) outcomes are challenging to monitor, necessitating advanced diagnostic tools.
• Urinary proteomics (UP) offers a non-invasive approach to assess graft health and patient status post-HTx.
• The uPROPHET study addresses the need for better methods to detect complications and guide immunosuppression.

Purpose of the Study:

• To develop multidimensional UP classifiers for detecting graft vasculopathy and monitoring immune activity after HTx.
• To identify key proteins involved in HTx complications through UP peptide fragment sequencing.
• To validate UP classifiers by comparing them with tissue proteomic (TP) signatures in explanted hearts and identify new drug targets.

Main Methods:

• Collection of mid-morning urine samples from HTx patients at the University Hospital Gasthuisberg.
• Acquisition of cardiac biopsies at the time of HTx for tissue proteomic analysis.
• Detailed description of UP and TP methodologies and statistical workflows within the study.

Main Results:

• The study enrolled 352 participants with diverse cardiomyopathy backgrounds.
• Baseline characteristics included a median age of 56.5 years and a median of 7.8 years post-HTx.
• A significant proportion of patients had a history of cellular or antibody-mediated rejection, highlighting the need for monitoring.

Conclusions:

• The uPROPHET database provides a robust resource for UP and TP research in heart transplantation.
• The study aims to establish the foundation for the clinical application of UP in risk stratification for HTx patients.
• This research has the potential to significantly improve patient management and outcomes after heart transplantation.