AUTHOR=Witczak Bartlomiej J. , Pischke Søren E. , Reisæter Anna V. , Midtvedt Karsten , Ludviksen Judith K. , Heldal Kristian , Jenssen Trond , Hartmann Anders , Åsberg Anders , Mollnes Tom E. 

TITLE=Elevated Terminal C5b-9 Complement Complex 10 Weeks Post Kidney Transplantation Was Associated With Reduced Long-Term Patient and Kidney Graft Survival

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.738927

DOI=10.3389/fimmu.2021.738927

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>The 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.</p></sec><sec><title>Methods</title><p>We 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].</p></sec><sec><title>Results</title><p>Elevated 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% <italic>vs</italic>. 75.5%, <italic>P</italic> &lt; 0.003). Similarly, 10-year graft survival was lower with elevated TCC; 56.9% <italic>vs</italic>. 67.3% (<italic>P</italic> &lt; 0.002). Graft survival was also lower when censored for death; 81.5% <italic>vs</italic>. 87.3% (<italic>P</italic> = 0.04). In multivariable Cox analyses, impaired patient survival was significantly associated with elevated TCC [hazard ratio (HR) 1.40 (1.02–1.91), <italic>P</italic> = 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), <italic>P</italic> = 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), <italic>P</italic> = 0.03] as were also HLA-DR mismatches and higher immunological risk.</p></sec><sec><title>Conclusions</title><p>Early complement activation, assessed by plasma TCC, was associated with impaired long-term patient and graft survival.</p></sec>