Systemic inflammation early after kidney transplantation is associated with long-term graft loss: a cohort study

Frontiers in Immunology

Immunology

Søren E. Pischke¹  Tom E. Mollnes²  Kristian Heldal³  Torbjørn F. Heldal⁴  Finn Reinholt⁵  Anna V. Reisæter⁶  Anders Åsberg⁷  Anders Hartmann⁸  Trond G. Jenssen⁸  Thor Ueland⁹  Pål Aukrust^1,10 

[1] Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway;Department of Anesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway;Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway;Research Laboratory, Nordland Hospital Bodø, Bodø, Norway;Department of Internal Medicine, Telemark Hospital Trust, Skien, Norway;Department of Transplantation Medicine, Oslo University Hospital – Rikshospitalet, Oslo, Norway;Institute of Health and Society, University of Oslo, Oslo, Norway;Department of Internal Medicine, Telemark Hospital Trust, Skien, Norway;Institute of Clinical Medicine, University of Oslo, Oslo, Norway;Department of Transplantation Medicine, Oslo University Hospital – Rikshospitalet, Oslo, Norway;Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway;Department of Transplantation Medicine, Oslo University Hospital – Rikshospitalet, Oslo, Norway;Norwegian Renal Registry, Oslo University Hospital – Rikshospitalet, Oslo, Norway;Department of Transplantation Medicine, Oslo University Hospital – Rikshospitalet, Oslo, Norway;Norwegian Renal Registry, Oslo University Hospital – Rikshospitalet, Oslo, Norway;Department of Pharmacy, University of Oslo, Oslo, Norway;Institute of Clinical Medicine, University of Oslo, Oslo, Norway;Department of Transplantation Medicine, Oslo University Hospital – Rikshospitalet, Oslo, Norway;Institute of Clinical Medicine, University of Oslo, Oslo, Norway;K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway;Research Institute of Internal Medicine, Oslo University Hospital - Rikshospitalet, Oslo, Norway;Institute of Clinical Medicine, University of Oslo, Oslo, Norway;K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway;Research Institute of Internal Medicine, Oslo University Hospital - Rikshospitalet, Oslo, Norway;Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital – Rikshospitalet, Oslo, Norway;

关键词: kidney transplantation;    inflammation;    graft failure;    graft loss;    biomarkers;   

DOI  :  10.3389/fimmu.2023.1253991

 received in 2023-07-06, accepted in 2023-09-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundEarly graft loss following kidney transplantation is mainly a result of acute rejection or surgical complications, while long-term kidney allograft loss is more complex. We examined the association between systemic inflammation early after kidney transplantation and long-term graft loss, as well as correlations between systemic inflammation scores and inflammatory findings in biopsies 6 weeks and 1 year after kidney transplantation.MethodsWe measured 21 inflammatory biomarkers 10 weeks after transplantation in 699 patients who were transplanted between 2009 and 2012 at Oslo University Hospital, Rikshospitalet, Norway. Low-grade inflammation was assessed with predefined inflammation scores based on specific biomarkers: one overall inflammation score and five pathway-specific scores. Surveillance or indication biopsies were performed in all patients 6 weeks after transplantation. The scores were tested in Cox regression models.ResultsMedian follow-up time was 9.1 years (interquartile range 7.6-10.7 years). During the study period, there were 84 (12.2%) death-censored graft losses. The overall inflammation score was associated with long-term kidney graft loss both when assessed as a continuous variable (hazard ratio 1.03, 95% CI 1.01-1.06, P = 0.005) and as a categorical variable (4th quartile: hazard ratio 3.19, 95% CI 1.43-7.10, P = 0.005). In the pathway-specific analyses, fibrogenesis activity and vascular inflammation stood out. The vascular inflammation score was associated with inflammation in biopsies 6 weeks and 1 year after transplantation, while the fibrinogenesis score was associated with interstitial fibrosis and tubular atrophy.ConclusionIn conclusion, a systemic inflammatory environment early after kidney transplantation was associated with biopsy-confirmed kidney graft pathology and long-term kidney graft loss. The systemic vascular inflammation score correlated with inflammatory findings in biopsies 6 weeks and 1 year after transplantation.

【 授权许可】

Unknown   
Copyright © 2023 Heldal, Åsberg, Ueland, Reisæter, Pischke, Mollnes, Aukrust, Reinholt, Hartmann, Heldal and Jenssen