Introduction

Chronic antibody-mediated rejection is thought to be the main cause of late kidney-allograft loss, involving donor-specific antibody–mediated activation of the complement system. Activation of filtered or locally produced complement may contribute to the progression of renal failure via tubular formation of the terminal C5b-9 complement complex. The aim of this study was to determine the urinary C5b-9 excretion and to assess its association with long-term outcome in renal transplant recipients (RTRs).

Methods

We measured urinary C5b-9 in a well-defined cross-sectional cohort of RTRs. Urinary specimens were taken from the morning urine portion and terminal complement component C5b-9 was measured using an enzyme-linked-immunosorbent assay (ELISA). Cox regression analyses were used to investigate prospective associations with death censored graft failure.

Results

We included 639 RTRs (age 53±13 years; 58% males at 5.3 (1.8-12.2) years after transplantation). Mean eGFR was 52.2±20.1 ml/min/1.73m², urinary C5b-9 excretion was detectable in 102 (16%) RTRs with median [interquartile range] C5b-9 levels of 5.1 (2.8-12.8) ng/mL. During follow-up of 4.9±1.6 years, 75 RTRs developed death censored graft failure. In univariable analysis, detectable C5b-9 was associated with increased risk of graft failure (HR 4.17 [95%CI 2.63-6.63], P<0.001) compared to undetectable C5b-9. The association of detectable C5b-9 with graft failure remained (HR 4.19 [95%CI 2.62-6.70], P<0.001) independent of adjustment for age, sex, and hs-CRP. Further adjustment for proteinuria>0.5 g/24h, did not materially alter the association of detectable C5b-9 with graft failure (HR 2.31 [95%CI 1.41-3.78], P=0.001).

Conclusion

Our results indicate that urinary C5b-9 is associated with graft failure, independently of potential confounders, including proteinuria. The results also suggest that urinary C5b-9 might be a useful biomarker for ongoing immunological injury and chronic kidney allograft deterioration. Our findings point towards a potential role for urinary complement activation in the pathogenesis of chronic allograft failure.

CITATION INFORMATION: Lammerts R., Eisenga M., Alyami M., Seelen M., Daha M., van den Born J., Bakker S., Berger S., On behalf of the COMBAT Comsortium Urinary C5b-9 is an Independent Predictor of Graft Failure in Renal Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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