title: A joint model for longitudinal and time-to-event data to better assess the specific role of donor and recipient factors on long-term kidney transplantation outcomes.
abstract: In renal transplantation, serum creatinine (SCr) is the main biomarker routinely measured to assess patient's health, with chronic increases being strongly associated with long-term graft failure risk (death with a functioning graft or return to dialysis). Joint modeling may be useful to identify the specific role of risk factors on chronic evolution of kidney transplant recipients: some can be related to the SCr evolution, finally leading to graft failure, whereas others can be associated with graft failure without any modification of SCr. Sample data for 2749 patients transplanted between 2000 and 2013 with a functioning kidney at 1-year post-transplantation were obtained from the DIVAT cohort. A shared random effect joint model for longitudinal SCr values and time to graft failure was performed. We show that graft failure risk depended on both the current value and slope of the SCr. Deceased donor graft patient seemed to have a higher SCr increase, similar to patient with diabetes history, while no significant association of these two features with graft failure risk was found. Patient with a second graft was at higher risk of graft failure, independent of changes in SCr values. Anti-HLA immunization was associated with both processes simultaneously. Joint models for repeated and time-to-event data bring new opportunities to improve the epidemiological knowledge of chronic diseases. For instance in renal transplantation, several features should receive additional attention as we demonstrated their correlation with graft failure risk was independent of the SCr evolution.
authors.affiliation: EA4275 SPHERE - bioStatistics, Pharmacoepidemiology and Human sciEnces REsearch, Nantes University, 1 rue Gaston Veil, 44035, Nantes, France.|Labex Transplantex, Inserm U1064, Institut de Transplantation Urologie Néphrologie (ITUN), Nantes University Hospital, Nantes, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Fournier
authors.affiliation: EA4275 SPHERE - bioStatistics, Pharmacoepidemiology and Human sciEnces REsearch, Nantes University, 1 rue Gaston Veil, 44035, Nantes, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Foucher
authors.affiliation: Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Paul
authors.initials: P
authors.lastname: Blanche
authors.affiliation: Service de Néphrologie, Transplantation et Immunologie Clinique, Hôpital Edouard Herriot, Lyon, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Buron
authors.affiliation: Labex Transplantex, Inserm U1064, Institut de Transplantation Urologie Néphrologie (ITUN), Nantes University Hospital, Nantes, France.|Centre d'investigation clinique biothérapie, Nantes, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Giral
authors.affiliation: EA4275 SPHERE - bioStatistics, Pharmacoepidemiology and Human sciEnces REsearch, Nantes University, 1 rue Gaston Veil, 44035, Nantes, France. Etienne.Dantan@univ-nantes.fr.
authors.forename: Etienne
authors.initials: E
authors.lastname: Dantan
mesh_terms: D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood*; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D019520:Living Donors; D008954:Models, Biological; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D003404:Creatinine
keywords: Graft failure; Joint modeling; Kidney transplantation; Repeated measurements; Serum creatinine; Time-to-event data
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