Metabolites (Jul 2022)
Preanalytical Pitfalls in Untargeted Plasma Nuclear Magnetic Resonance Metabolomics of Endocrine Hypertension
- Nikolaos G. Bliziotis,
- Leo A. J. Kluijtmans,
- Gerjen H. Tinnevelt,
- Parminder Reel,
- Smarti Reel,
- Katharina Langton,
- Mercedes Robledo,
- Christina Pamporaki,
- Alessio Pecori,
- Josie Van Kralingen,
- Martina Tetti,
- Udo F. H. Engelke,
- Zoran Erlic,
- Jasper Engel,
- Timo Deutschbein,
- Svenja Nölting,
- Aleksander Prejbisz,
- Susan Richter,
- Jerzy Adamski,
- Andrzej Januszewicz,
- Filippo Ceccato,
- Carla Scaroni,
- Michael C. Dennedy,
- Tracy A. Williams,
- Livia Lenzini,
- Anne-Paule Gimenez-Roqueplo,
- Eleanor Davies,
- Martin Fassnacht,
- Hanna Remde,
- Graeme Eisenhofer,
- Felix Beuschlein,
- Matthias Kroiss,
- Emily Jefferson,
- Maria-Christina Zennaro,
- Ron A. Wevers,
- Jeroen J. Jansen,
- Jaap Deinum,
- Henri J. L. M. Timmers
Affiliations
- Nikolaos G. Bliziotis
- Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
- Leo A. J. Kluijtmans
- Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
- Gerjen H. Tinnevelt
- Department of Analytical Chemistry, Institute for Molecules and Materials, Radboud University, 6500 HB Nijmegen, The Netherlands
- Parminder Reel
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee DD2 4BF, UK
- Smarti Reel
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee DD2 4BF, UK
- Katharina Langton
- Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
- Mercedes Robledo
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain
- Christina Pamporaki
- Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
- Alessio Pecori
- Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Torino, 10124 Torino, Italy
- Josie Van Kralingen
- British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), Institute of Cardiovascular & Medical Sciences (ICAMS), University of Glasgow, Glasgow G12 8TA, UK
- Martina Tetti
- Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Torino, 10124 Torino, Italy
- Udo F. H. Engelke
- Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
- Zoran Erlic
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ), University of Zurich (UZH), 8006 Zurich, Switzerland
- Jasper Engel
- Biometris, Wageningen University & Research, 6708 PB Wageningen, The Netherlands
- Timo Deutschbein
- Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Würzburg, Germany
- Svenja Nölting
- Department of Medicine IV, University Hospital, LMU Munich, 80336 Munich, Germany
- Aleksander Prejbisz
- Department of Hypertension, Institute of Cardiology, 04-628 Warsaw, Poland
- Susan Richter
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the Technische Universität Dresden, 01307 Dresden, Germany
- Jerzy Adamski
- Research Unit Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Center München, German Research Center for Environmental Health, 85764 Neuherberg, Germany
- Andrzej Januszewicz
- Department of Hypertension, Institute of Cardiology, 04-628 Warsaw, Poland
- Filippo Ceccato
- Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, 35128 Padova, Italy
- Carla Scaroni
- Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, 35128 Padova, Italy
- Michael C. Dennedy
- The Discipline of Pharmacology and Therapeutics, School of Medicine, National University of Ireland, H91 CF50 Galway, Ireland
- Tracy A. Williams
- Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Torino, 10124 Torino, Italy
- Livia Lenzini
- Department of Medicine-DIMED, Emergency and Hypertension Unit, University of Padova, University Hospital, 35126 Padova, Italy
- Anne-Paule Gimenez-Roqueplo
- INSERM, PARCC, Université de Paris, 75015 Paris, France
- Eleanor Davies
- British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), Institute of Cardiovascular & Medical Sciences (ICAMS), University of Glasgow, Glasgow G12 8TA, UK
- Martin Fassnacht
- Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Würzburg, Germany
- Hanna Remde
- Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Würzburg, Germany
- Graeme Eisenhofer
- Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
- Felix Beuschlein
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ), University of Zurich (UZH), 8006 Zurich, Switzerland
- Matthias Kroiss
- Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Würzburg, Germany
- Emily Jefferson
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee DD2 4BF, UK
- Maria-Christina Zennaro
- INSERM, PARCC, Université de Paris, 75015 Paris, France
- Ron A. Wevers
- Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
- Jeroen J. Jansen
- Department of Analytical Chemistry, Institute for Molecules and Materials, Radboud University, 6500 HB Nijmegen, The Netherlands
- Jaap Deinum
- Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
- Henri J. L. M. Timmers
- Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
- DOI
- https://doi.org/10.3390/metabo12080679
- Journal volume & issue
-
Vol. 12,
no. 8
p. 679
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.
Keywords
