Impact Factor 4.716 | CiteScore 4.71
More on impact ›

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02511

Urinary Properdin and sC5b-9 are Independently Associated with Increased Risk for Graft Failure in Renal Transplant Recipients

  • 1University Medical Center Groningen, Netherlands

Abstract
The pathophysiology of late kidney-allograft failure remains complex and poorly understood. Activation of filtered or locally produced complement may contribute to the progression of renal failure through tubular C5b-9 formation. This study aimed to determine urinary properdin and sC5b-9 excretion and assess its association with long-term outcome in renal transplant recipients (RTR).
Methods
We measured urinary properdin and soluble C5b-9 in a well-defined cross-sectional cohort of RTR. Urinary specimens were taken from the morning urine portion and properdin and sC5b-9 were measured using an enzyme-linked- immunosorbent assay (ELISA). Cox proportional hazard regression analyses were used to investigate prospective associations with death-censored graft failure.
Results
We included 639 stable RTR at a median [interquartile range] 5.3 (1.8-12.2) years after transplantation. Urinary properdin and sC5b-9 excretion were detectable in 161 (27%) and 102 (17%) RTR respectively, with a median properdin level of 27.6 (8.6-68.1) ng/mL and a median sC5b-9 level of 5.1 (2.8-12.8) ng/mL. In multivariable-adjusted Cox regression analyses, including adjustment for proteinuria, urinary properdin (HR 1.12; 95% CI 1.02-1.28; P=0.008) and sC5b-9 excretion (HR 1.34; 95% CI 1.10-1.63; P=0.003) were associated with an increased risk of graft failure. If both urinary properdin and sC5b-9 were detectable, the risk of graft failure was further increased(HR 3.12; 95% CI 1.69-5.77; P<0.001).
Conclusions
Our findings point towards a potential role for urinary complement activation in the pathogenesis of chronic allograft failure. Urinary properdin and sC5b-9 might be useful biomarkers for complement activation and chronic kidney allograft deterioration, suggesting a potential role for an alternative pathway blockade in RTR.

Keywords: Transplantation, chronic renal failure, Properdin, C5b-9, Complement Activation

Received: 12 Aug 2019; Accepted: 08 Oct 2019.

Copyright: © 2019 Lammerts, Eisenga, Alyami, Seelen, Pol, Van Den Born, Sanders, Bakker and Berger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD. Rosa G. Lammerts, University Medical Center Groningen, Groningen, Netherlands, r.g.m.lammerts@umcg.nl