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Elevated Terminal C5b-9 Complement Complex 10 Weeks Post Kidney Transplantation Was Associated With Reduced Long-Term Patient and Kidney Graft Survival
oleh: Bartlomiej J. Witczak, Søren E. Pischke, Søren E. Pischke, Anna V. Reisæter, Anna V. Reisæter, Karsten Midtvedt, Judith K. Ludviksen, Kristian Heldal, Trond Jenssen, Trond Jenssen, Anders Hartmann, Anders Hartmann, Anders Åsberg, Anders Åsberg, Anders Åsberg, Tom E. Mollnes, Tom E. Mollnes, Tom E. Mollnes, Tom E. Mollnes
| Format: | Article |
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| Diterbitkan: | Frontiers Media S.A. 2021-10-01 |
Deskripsi
BackgroundThe major reason for graft loss is chronic tissue damage, as interstitial fibrosis and tubular atrophy (IF/TA), where complement activation may serve as a mediator. The association of complement activation in a stable phase early after kidney transplantation with long-term outcomes is unexplored.MethodsWe examined plasma terminal C5b-9 complement complex (TCC) 10 weeks posttransplant in 900 patients receiving a kidney between 2007 and 2012. Clinical outcomes were assessed after a median observation time of 9.3 years [interquartile range (IQR) 7.5–10.6].ResultsElevated TCC plasma values (≥0.7 CAU/ml) were present in 138 patients (15.3%) and associated with a lower 10-year patient survival rate (65.7% vs. 75.5%, P < 0.003). Similarly, 10-year graft survival was lower with elevated TCC; 56.9% vs. 67.3% (P < 0.002). Graft survival was also lower when censored for death; 81.5% vs. 87.3% (P = 0.04). In multivariable Cox analyses, impaired patient survival was significantly associated with elevated TCC [hazard ratio (HR) 1.40 (1.02–1.91), P = 0.04] along with male sex, recipient and donor age, smoking, diabetes, and overall survival more than 1 year in renal replacement therapy prior to engraftment. Likewise, elevated TCC was independently associated with graft loss [HR 1.40 (1.06–1.85), P = 0.02] along with the same covariates. Finally, elevated TCC was in addition independently associated with death-censored graft loss [HR 1.69 (1.06–2.71), P = 0.03] as were also HLA-DR mismatches and higher immunological risk.ConclusionsEarly complement activation, assessed by plasma TCC, was associated with impaired long-term patient and graft survival.