Preanalytical Pitfalls in Untargeted Plasma Nuclear Magnetic Resonance Metabolomics of Endocrine Hypertension

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Nikolaos G. Bliziotis - , Radboud University Nijmegen (Author)
  • Leo A.J. Kluijtmans - , Radboud University Nijmegen (Author)
  • Gerjen H. Tinnevelt - , Radboud University Nijmegen (Author)
  • Parminder Reel - , University of Dundee (Author)
  • Smarti Reel - , University of Dundee (Author)
  • Katharina Langton - , University Medicine (Faculty of Medicine and University Hospital), Department of Gynecology and Obstetrics, TUD Dresden University of Technology (Author)
  • Mercedes Robledo - , Instituto de Salud Carlos III (Author)
  • Christina Pamporaki - , Center for Information Services and High Performance Computing (ZIH), Department of internal Medicine 3, TUD Dresden University of Technology (Author)
  • Alessio Pecori - , University of Turin (Author)
  • Josie Van Kralingen - , University of Glasgow (Author)
  • Martina Tetti - , University of Turin (Author)
  • Udo F.H. Engelke - , Radboud University Nijmegen (Author)
  • Zoran Erlic - , University of Zurich (Author)
  • Jasper Engel - , Wageningen University & Research (WUR) (Author)
  • Timo Deutschbein - , University of Würzburg, Medicover Oldenburg MVZ (Author)
  • Svenja Nölting - , Ludwig Maximilian University of Munich (Author)
  • Aleksander Prejbisz - , Cardinal Stefan Wyszynski Institute of Cardiology (Author)
  • Susan Richter - , Institute of Clinical Chemistry and Laboratory Medicine (Author)
  • Jerzy Adamski - , University of Ljubljana, Technical University of Munich, National University of Singapore, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Andrzej Januszewicz - , Cardinal Stefan Wyszynski Institute of Cardiology (Author)
  • Filippo Ceccato - , Azienda Ospedaliera di Padova (Author)
  • Carla Scaroni - , Azienda Ospedaliera di Padova (Author)
  • Michael C. Dennedy - , University of Galway (Author)
  • Tracy A. Williams - , University of Turin (Author)
  • Livia Lenzini - , University of Padua (Author)
  • Anne Paule Gimenez-Roqueplo - , Université Paris Cité, Hopital Europeen Georges-Pompidou (Author)
  • Eleanor Davies - , University of Glasgow (Author)
  • Martin Fassnacht - , University of Würzburg (Author)
  • Hanna Remde - , University of Würzburg (Author)
  • Graeme Eisenhofer - , Institute of Clinical Chemistry and Laboratory Medicine (Author)
  • Felix Beuschlein - , University of Zurich, Ludwig Maximilian University of Munich (Author)
  • Matthias Kroiss - , University of Würzburg, Ludwig Maximilian University of Munich (Author)
  • Emily Jefferson - , University of Dundee, University of Glasgow (Author)
  • Maria Christina Zennaro - , Université Paris Cité, Hopital Europeen Georges-Pompidou (Author)
  • Ron A. Wevers - , Radboud University Nijmegen (Author)
  • Jeroen J. Jansen - , Radboud University Nijmegen (Author)
  • Jaap Deinum - , Radboud University Nijmegen (Author)
  • Henri J.L.M. Timmers - , Radboud University Nijmegen (Author)

Abstract

Despite considerable morbidity and mortality, numerous cases of endocrine hypertension (EHT) forms, including primary aldosteronism (PA), pheochromocytoma and functional paraganglioma (PPGL), and Cushing’s syndrome (CS), remain undetected. We aimed to establish signatures for the different forms of EHT, investigate potentially confounding effects and establish unbiased disease biomarkers. Plasma samples were obtained from 13 biobanks across seven countries and analyzed using untargeted NMR metabolomics. We compared unstratified samples of 106 PHT patients to 231 EHT patients, including 104 PA, 94 PPGL and 33 CS patients. Spectra were subjected to a multivariate statistical comparison of PHT to EHT forms and the associated signatures were obtained. Three approaches were applied to investigate and correct confounding effects. Though we found signatures that could separate PHT from EHT forms, there were also key similarities with the signatures of sample center of origin and sample age. The study design restricted the applicability of the corrections employed. With the samples that were available, no biomarkers for PHT vs. EHT could be identified. The complexity of the confounding effects, evidenced by their robustness to correction approaches, highlighted the need for a consensus on how to deal with variabilities probably attributed to preanalytical factors in retrospective, multicenter metabolomics studies.

Details

Original languageEnglish
Article number679
JournalMetabolites
Volume12
Issue number8
Publication statusPublished - Aug 2022
Peer-reviewedYes

External IDs

ORCID /0000-0002-3549-2477/work/142244887

Keywords

Sustainable Development Goals

Keywords

  • confounders, metabolomics, multicenter, plasma NMR, preanalytical conditions