Elisabet Van Loon1,2, Evelyne Lerut3,4, Aleksandar Senev1,5, Maarten Coemans1,6, Jacques Pirenne1,7, Diethard Monbaliu1,7, Ina Jochmans1,7, Mauricio Sainz Barriga1,7, Katrien De Vusser1,2, Amaryllis H Van Craenenbroeck1,2, Ben Sprangers1,2,8, Marie-Paule Emonds1,4,5, Dirk Kuypers1,2, Maarten Naesens9,2. 1. Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, Leuven, Belgium. 2. Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. 3. Department of Imaging and Pathology, Katholieke Universiteit Leuven, Leuven, Belgium. 4. Department of Pathology, University Hospitals Leuven, Leuven, Belgium. 5. Histocompatibility and Immunogenetics Laboratory, Red Cross-Flanders, Mechelen, Belgium. 6. Department of Public Health and Primary Care, Leuven Biostatistics and Statistical Bioinformatics Centre, Katholieke Universiteit Leuven, Leuven, Belgium. 7. Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium. 8. Laboratory of Molecular Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium. 9. Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, Leuven, Belgium maarten.naesens@kuleuven.be.
Abstract
BACKGROUND AND OBJECTIVES: In preclinical studies, ischemia-reperfusion injury and older donor age are associated with graft inflammation in the early phase after transplantation. In human kidney transplantation, impaired allograft function in the first days after transplantation is often adjudicated to donor- and procedure-related characteristics, such as donor age, donor type, and ischemia times. DESIGN: , setting, participants, & measurementsIn a cohort of 984 kidney recipients, 329 indication biopsies were performed within the first 14 days after transplantation. The histologic picture of these biopsies and its relationship with alloimmune risk factors and donor- and procedure-related characteristics were studied, as well as the association with graft failure. Multivariable Cox models were applied to quantify the cause-specific hazard ratios for early rejection and early inflammatory scores, adjusted for potential confounders. For quantification of hazard ratios of early events for death-censored graft failure, landmark analyses starting from day 15 were used. RESULTS: Early indication biopsy specimens displayed microvascular inflammation score ≥2 in 30% and tubulointerstitial inflammation score ≥2 in 49%. Rejection was diagnosed in 186 of 329 (57%) biopsies and associated with the presence of pretransplant donor-specific HLA antibodies and the number of HLA mismatches, but not nonimmune risk factors in multivariable Cox proportional hazards analysis. In multivariable Cox proportional hazards analysis, delayed graft function, the graft dysfunction that prompted an early indication biopsy, HLA mismatches, and pretransplant donor-specific HLA antibodies were significantly associated with a higher risk for death-censored graft failure, whereas early acute rejection was not. CONCLUSIONS: Indication biopsies performed early after kidney transplantation display inflammatory changes related to alloimmune risk factors. Nonimmune risk factors for ischemia-reperfusion injury, such as cold and warm ischemia time, older donor age, and donor type, were not identified as strong risk factors for early inflammation after human kidney transplantation.
BACKGROUND AND OBJECTIVES: In preclinical studies, ischemia-reperfusion injury and older donor age are associated with graft inflammation in the early phase after transplantation. In human kidney transplantation, impaired allograft function in the first days after transplantation is often adjudicated to donor- and procedure-related characteristics, such as donor age, donor type, and ischemia times. DESIGN: , setting, participants, & measurementsIn a cohort of 984 kidney recipients, 329 indication biopsies were performed within the first 14 days after transplantation. The histologic picture of these biopsies and its relationship with alloimmune risk factors and donor- and procedure-related characteristics were studied, as well as the association with graft failure. Multivariable Cox models were applied to quantify the cause-specific hazard ratios for early rejection and early inflammatory scores, adjusted for potential confounders. For quantification of hazard ratios of early events for death-censored graft failure, landmark analyses starting from day 15 were used. RESULTS: Early indication biopsy specimens displayed microvascular inflammation score ≥2 in 30% and tubulointerstitial inflammation score ≥2 in 49%. Rejection was diagnosed in 186 of 329 (57%) biopsies and associated with the presence of pretransplant donor-specific HLA antibodies and the number of HLA mismatches, but not nonimmune risk factors in multivariable Cox proportional hazards analysis. In multivariable Cox proportional hazards analysis, delayed graft function, the graft dysfunction that prompted an early indication biopsy, HLA mismatches, and pretransplant donor-specific HLA antibodies were significantly associated with a higher risk for death-censored graft failure, whereas early acute rejection was not. CONCLUSIONS: Indication biopsies performed early after kidney transplantation display inflammatory changes related to alloimmune risk factors. Nonimmune risk factors for ischemia-reperfusion injury, such as cold and warm ischemia time, older donor age, and donor type, were not identified as strong risk factors for early inflammation after human kidney transplantation.
Authors: Christian Denecke; Xiaodong Yuan; Xupeng Ge; Irene K Kim; Daman Bedi; Olaf Boenisch; Anne Weiland; Anke Jurisch; Katja Kotsch; Johann Pratschke; Anja Reutzel-Selke; Stefan G Tullius Journal: Surgery Date: 2012-10-09 Impact factor: 3.982
Authors: Johan W DE Fijter; Marko J K Mallat; Ilias I N Doxiadis; Jan Ringers; Frits R Rosendaal; Frans H J Claas; Leendert C Paul Journal: J Am Soc Nephrol Date: 2001-07 Impact factor: 10.121
Authors: B Mirshekar-Syahkal; D Summers; L L Bradbury; M Aly; V Bardsley; M Berry; J M Norris; N Torpey; M R Clatworthy; J A Bradley; G J Pettigrew Journal: Am J Transplant Date: 2016-08-26 Impact factor: 8.086
Authors: Merve Postalcioglu; Arnaud D Kaze; Benjamin C Byun; Andrew Siedlecki; Stefan G Tullius; Edgar L Milford; Julie M Paik; Reza Abdi Journal: Transplantation Date: 2018-07 Impact factor: 4.939
Authors: Alexander Schaapherder; Leonie G M Wijermars; Dorottya K de Vries; Aiko P J de Vries; Frederike J Bemelman; Jacqueline van de Wetering; Arjan D van Zuilen; Maarten H L Christiaans; Luuk H Hilbrands; Marije C Baas; Azam S Nurmohamed; Stefan P Berger; Ian P Alwayn; Esther Bastiaannet; Jan H N Lindeman Journal: EClinicalMedicine Date: 2018-10-09
Authors: M Haas; A Loupy; C Lefaucheur; C Roufosse; D Glotz; D Seron; B J Nankivell; P F Halloran; R B Colvin; Enver Akalin; N Alachkar; S Bagnasco; Y Bouatou; J U Becker; L D Cornell; J P Duong van Huyen; I W Gibson; Edward S Kraus; R B Mannon; M Naesens; V Nickeleit; P Nickerson; D L Segev; H K Singh; M Stegall; P Randhawa; L Racusen; K Solez; M Mengel Journal: Am J Transplant Date: 2018-01-21 Impact factor: 8.086
Authors: Mayuko Uehara; Zhabiz Solhjou; Naima Banouni; Vivek Kasinath; Ye Xiaqun; Li Dai; Osman Yilmam; Mine Yilmaz; Takaharu Ichimura; Paolo Fiorina; Paulo N Martins; Shunsuke Ohori; Indira Guleria; Omar H Maarouf; Stefan G Tullius; Martina M McGrath; Reza Abdi Journal: Sci Rep Date: 2018-02-06 Impact factor: 4.379
Authors: João Batista Saldanha De Castro Filho; Jeferson De Castro Pompeo; Rafael Berlezi Machado; Luiz Felipe Santos Gonçalves; Andrea Carla Bauer; Roberto Ceratti Manfro Journal: Transpl Int Date: 2022-03-24 Impact factor: 3.782