
Background. There are challenges in designing adequate, well-controlled studies of patients with active antibody-mediated rejection (AMR) after kidney transplantation (KTx). Methods. We assessed the functional relationship between change in estimated glomerular filtration rate (eGFR) following the diagnosis of AMR and the risk of subsequent death-censored graft failure using the joint modeling framework. We included recipients of solitary KTx between 1995 and 2013 at 4 transplant centers diagnosed with biopsy-proven active AMR at least 1 year post-KTx, who had a minimum of 3-year follow-up. Results. A total of 91 patients across participating centers were included in the analysis. Of the 91 patients, n = 54 patients (59%) met the death-censored graft failure endpoint and n = 62 patients (68%) met the all-cause graft failure composite endpoint. Kaplan-Meier death-censored graft survival rates at 12, 36, and 60 months postdiagnosis of AMR pooled across centers were 88.9%, 58.9%, and 36.4%, respectively. Spaghetti plots indicated a linear trend in the change in eGFR, especially in the first 12 months postdiagnosis of active AMR. A significant change in eGFR was observed within the first 12 months postdiagnosis of active AMR, getting worse by a factor of −0.757 mL/min/1.73 m2 per month during the 12-month analysis period (a delta of −9.084 mL/min/1.73 m2 at 1 y). Notably, an extrapolated 30% improvement in the slope of eGFR in the first 12 months was associated with a 10% improvement in death-censored graft failure at 5 years. Conclusions. If prospectively validated, this study may inform the design of pivotal clinical trials for therapies for late AMR.
Adult, Graft Rejection, Male, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::intervenciones quirúrgicas::trasplante::trasplante de órganos::intervenciones quirúrgicas::trasplante de riñón, Time Factors, Biopsy, Kidney, Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos, Humans, Retrospective Studies, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Surgical Procedures, Operative::Transplantation::Organ Transplantation::Surgical Procedures, Operative::Kidney Transplantation, Graft Survival, Allografts, Kidney Transplantation, Rebuig (Biologia), Other subheadings::Other subheadings::Other subheadings::/adverse effects, FENÓMENOS Y PROCESOS::fenómenos del sistema inmunitario::inmunología del trasplante::reacción huésped contra injerto::rechazo del injerto, Acute Disease, Female, PHENOMENA AND PROCESSES::Immune System Phenomena::Transplantation Immunology::Host vs Graft Reaction::Graft Rejection, Ronyons - Trasplantació - Complicacions, Follow-Up Studies, Glomerular Filtration Rate
Adult, Graft Rejection, Male, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::intervenciones quirúrgicas::trasplante::trasplante de órganos::intervenciones quirúrgicas::trasplante de riñón, Time Factors, Biopsy, Kidney, Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos, Humans, Retrospective Studies, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Surgical Procedures, Operative::Transplantation::Organ Transplantation::Surgical Procedures, Operative::Kidney Transplantation, Graft Survival, Allografts, Kidney Transplantation, Rebuig (Biologia), Other subheadings::Other subheadings::Other subheadings::/adverse effects, FENÓMENOS Y PROCESOS::fenómenos del sistema inmunitario::inmunología del trasplante::reacción huésped contra injerto::rechazo del injerto, Acute Disease, Female, PHENOMENA AND PROCESSES::Immune System Phenomena::Transplantation Immunology::Host vs Graft Reaction::Graft Rejection, Ronyons - Trasplantació - Complicacions, Follow-Up Studies, Glomerular Filtration Rate
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