Highlights
- •The measurement of serum levels of complement factor C3 constitutes a routine practice in most clinical immunology laboratories.
- •C3 hypocomplementemia at month 6 after kidney transplantation was associated with a three-fold increase in the risk of atherothrombotic events.
- •This association was independent of other well-established risk factors for cardiovascular disease.
- •The inclusion of this parameter improves the accuracy of clinical predictive models for post-transplant cardiovascular disease.
Abstract
Background and aims
Cardiovascular disease (CVD) is a leading cause of mortality after kidney transplantation
(KT). The potential role of the complement system in the pathogenesis of post-transplant
CVD remains unexplored.
Methods
Serum complement (C3 and C4) levels were measured at baseline and post-transplant
months 1 and 6 in 447 kT recipients. The study outcome was post-transplant atherothrombotic
event (PAE), a composite of acute coronary syndrome, critical peripheral arterial
disease, stroke and/or transient ischemic attack.
Results
After a median follow-up of 4.2 years, 48 PAEs occurred in 43 patients (cumulative
incidence: 9.6%; incidence rate: 2.6 events per 100 transplant-years). No differences
were found in C3 and C4 levels at baseline or month 1 between patients with or without
PAE. However, C3 levels at month 6 were significantly lower in patients developing
PAE beyond that point (i.e., late PAE) (96.9 ± 22.3 vs. 109.6 ± 24.0 mg/dL; p = 0.013). The presence of C3 hypocomplementemia at month 6 was associated with a
lower PAE-free survival (p = 0.002). After adjusting for conventional CVD risk factors and acute graft rejection,
C3 hypocomplementemia at month 6 remained as an independent risk factor for late PAE
in all the exploratory models (minimum hazard ratio: 3.24; p = 0.011). With respect to a model exclusively based on clinical variables, the inclusion
of C3 levels at month 6 improved predictive capacity (areas under ROC curves: 0.788
and 0.812, respectively).
Conclusions
Post-transplant monitoring of serum C3 levels might be useful to identify KT recipients
at increased risk of CVD.
Keywords
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Article info
Publication history
Published online: January 19, 2018
Accepted:
January 12,
2018
Received in revised form:
December 22,
2017
Received:
May 29,
2017
Footnotes
☆This study was partially presented at the IV Congress of the Spanish Society of Transplantation (SET), Santander, May 6-8, 2016.
Identification
Copyright
© 2018 Elsevier B.V. All rights reserved.
