[en] [en] BACKGROUND: Despite the increasing number of biomarker studies published in the transplant literature over the past 20 years, demonstrations of their clinical benefit and their implementation in routine clinical practice are lacking. We hypothesized that suboptimal design, data, methodology and reporting might contribute to this phenomenon.
METHODS: A systematic literature search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library between 1 January 2005 and 12 November 2022 (PROSPERO ID: CRD42020154747). All English language, original studies investigating the association between a biomarker and kidney-allograft outcome were included. The final set of publications was assessed by expert reviewers. After data collection, two independent reviewers randomly evaluated the inconsistencies for 30% of the references for each reviewer. If more than 5% of inconsistencies were observed for one given reviewer, a re-evaluation was conducted for all the references of the reviewer. The biomarkers were categorized according to their type and the biological milieu from which they were measured. The study characteristics related to the design, methods, results, and their interpretation were assessed, as well as reproducible research practices and transparency indicators.
RESULTS: A total of 7372 publications were screened and 804 studies met the inclusion criteria. A total of 1143 biomarkers were assessed among the included studies from blood (n=821, 71.8%), intragraft (n=169, 14.8%), or urine (n=81, 7.1%) compartments. The number of studies significantly increased, with a median, yearly number of 31.5 studies (IQR: 23.8-35.5) between 2005 and 2012, and 57.5 (IQR: 53.3-59.8) between 2013 and 2022 (p<0.001). A total of 655 studies (81.5%) were retrospective, while 595 (74.0%) used data from a single center. The median number of patients included was 232 (IQR: 96-629) with a median follow-up posttransplant of 4.8 years (IQR: 3.0-6.2). Only 4.7% of studies were externally validated. A total of 346 studies (43.0%) did not adjust their biomarker for key prognostic factors while only 3.1% of studies adjusted the biomarker for standard-of-care patient monitoring factors. Data sharing, code sharing, and registration occurred in 8.8%, 1.1%, and 4.6% of studies, respectively. A total of 158 studies (20.0%) emphasized the clinical relevance of the biomarker despite the reported nonsignificant association of the biomarker with the outcome measure. A total of 288 studies assessed rejection as an outcome. We showed that these rejection studies shared the same characteristics as other studies.
CONCLUSIONS: and Relevance Biomarker studies in kidney transplantation lack validation, rigorous design, methods and interpretation, and transparency. Higher standards in biomarker research may improve the clinical utility and clinical use.
Disciplines :
General & internal medicine
Author, co-author :
Raynaud, Marc; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France
Al-Awadhi, Solaf ; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France
Louis, Kevin ; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France
Zhang, Huanxi ; The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Su, Xiaojun; The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Goutaudier, Valentin ; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France
Wang, Jiali; The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Demir, Zeynep ; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France
Wei, Yongcheng ; The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Truchot, Agathe; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France
Bouquegneau, Antoine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de néphrologie
Del Bello, Arnaud ; Université Paul Sabatier, INSERM, Department of Nephrology and Organ Transplantation, CHU Rangueil & Purpan, Toulouse, France
Bailly, Élodie ; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France ; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Lombardi, Yannis ; Kidney Transplant Department, Tenon Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
Maanaoui, Mehdi; Lille University, CHU Lille, Nephrology Department, F-59037, Lille, France, INSERM U1190, Translational Research for Diabetes, Lille, France
Giarraputo, Alessia ; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France ; Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
Naser, Sofia ; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France
Divard, Gillian ; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France
Aubert, Olivier ; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France
Murad, Mohammad Hassan ; Evidence-Based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
Wang, Changxi; The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Liu, Longshan ; The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Naesens, Maarten ; Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium
Friedewald, John J ; Division of Transplantation, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Lefaucheur, Carmen ; Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
Riella, Leonardo ; Schuster Family Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Collins, Gary ; Center for Statistics in Medicine, NDORMS, Botnar Research Center, University of Oxford, Oxford, UK
Ioannidis, John P A ; Departments of Medicine, of Epidemiology and Population Health, of Biomedical Data Science, and of Statistics and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, USA
Loupy, Alexandre; Université de Paris Cité, INSERM, PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France
H2020 - 754995 - EU-TRAIN - The EUropean TRAnsplantation and INnovation (EU-TRAIN) consortium for improving diagnosis and risk stratification in kidney transplant patients
Funders :
ANR - Agence Nationale de la Recherche [FR] EU - European Union [BE] MSD Avenir [FR] OrganX [CH]
Funding text :
ANR-17-RHUS-0010/French government financial support managed by the National Research Agency (ANR) under the program for Investissements d'avenir KTD-Innov; 754995/European Union's Horizon 2020 research and innovation program EU-TRAIN
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