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Post-transplant hypocomplementemia: A novel marker of cardiovascular risk in kidney transplant recipients?

  • Guillermo Maestro de la Calle
    Affiliations
    Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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  • Mario Fernández-Ruiz
    Correspondence
    Corresponding author. Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Centro de Actividades Ambulatorias, 2a planta, bloque D. Avda. de Córdoba, s/n., 28041, Madrid, Spain.
    Affiliations
    Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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  • Francisco López-Medrano
    Affiliations
    Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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  • Natalia Polanco
    Affiliations
    Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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  • Esther González
    Affiliations
    Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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  • Rafael San Juan
    Affiliations
    Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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  • Tamara Ruiz-Merlo
    Affiliations
    Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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  • Julia Origüen
    Affiliations
    Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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  • Estela Paz-Artal
    Affiliations
    Department of Immunology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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  • Amado Andrés
    Affiliations
    Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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  • José María Aguado
    Affiliations
    Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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      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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