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

PLoS One. 2017 Sep 7;12(9):e0184443. doi: 10.1371/journal.pone.0184443. eCollection 2017.

Abstract

Objectives: Urinary Proteomics in Predicting Heart Transplantation Outcomes (uPROPHET; NCT03152422) aims: (i) to construct new multidimensional urinary proteomic (UP) classifiers that after heart transplantation (HTx) help in detecting graft vasculopathy, monitoring immune system activity and graft performance, and in adjusting immunosuppression; (ii) to sequence UP peptide fragments and to identify key proteins mediating HTx-related complications; (iii) to validate UP classifiers by demonstrating analogy between UP profiles and tissue proteomic signatures (TP) in diseased explanted hearts, to be compared with normal donor hearts; (iv) and to identify new drug targets. This article describes the uPROPHET database construction, follow-up strategies and baseline characteristics of the HTx patients.

Methods: HTx patients enrolled at the University Hospital Gasthuisberg (Leuven) collected mid-morning urine samples. Cardiac biopsies were obtained at HTx. UP and TP methods and the statistical work flow in pursuit of the research objectives are described in detail in the Data supplement.

Results: Of 352 participants in the UP study (24.4% women), 38.9%, 40.3%, 5.7% and 15.1% had ischemic, dilated, hypertrophic or other cardiomyopathy. The median interval between HTx and first UP assessment (baseline) was 7.8 years. At baseline, mean values were 56.5 years for age, 25.2 kg/m2 for body mass index, 142.3/84.8 mm Hg and 124.2/79.8 mm Hg for office and 24-h ambulatory systolic/diastolic pressure, and 58.6 mL/min/1.73 m2 for the estimated glomerular filtration rate. Of all patients, 37.2% and 6.5% had a history of mild (grade = 1B) or severe (grade ≥ 2) cellular rejection. Anti-body mediated rejection had occurred in 6.2% patients. The number of follow-up urine samples available for future analyses totals over 950. The TP study currently includes biopsies from 7 healthy donors and 15, 14, and 3 patients with ischemic, dilated, and hypertrophic cardiomyopathy.

Conclusions: uPROPHET constitutes a solid resources for UP and TP research in the field of HTx and has the ambition to lay the foundation for the clinical application of UP in risk stratification in HTx patients.

MeSH terms

  • Cardiomyopathies / surgery
  • Cardiomyopathies / urine
  • Databases, Factual*
  • Female
  • Graft Rejection
  • Heart Transplantation*
  • Humans
  • Immunosuppression
  • Male
  • Proteomics / methods*

Grant support

This work was supported by the European Union (HEALTH-F7-305507 HOMAGE, URL: http://www.homage-hf.eu/) and the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET; URL: http://cordis.europa.eu/project/rcn/104182_en.html and http://cordis.europa.eu/project/rcn/205861_en.html) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13, URL: http://www.fwo.be/) currently support the Studies Coordinating Centre in Leuven. The EPLORE grant paid for the urinary proteomic measurements at Mosaiques Diagnostics AG (Hannover, Germany). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.