Vitamin C Depletion and All-Cause Mortality in Renal Transplant Recipients

Camilo G Sotomayor, Michele F Eisenga, Antonio W Gomes Neto, Akin Ozyilmaz, Rijk O B Gans, Wilhelmina H A de Jong, Dorien M Zelle, Stefan P Berger, Carlo A J M Gaillard, Gerjan J Navis, Stephan J L Bakker, Camilo G Sotomayor, Michele F Eisenga, Antonio W Gomes Neto, Akin Ozyilmaz, Rijk O B Gans, Wilhelmina H A de Jong, Dorien M Zelle, Stefan P Berger, Carlo A J M Gaillard, Gerjan J Navis, Stephan J L Bakker

Abstract

Vitamin C may reduce inflammation and is inversely associated with mortality in the general population. We investigated the association of plasma vitamin C with all-cause mortality in renal transplant recipients (RTR); and whether this association would be mediated by inflammatory biomarkers. Vitamin C, high sensitive C-reactive protein (hs-CRP), soluble intercellular cell adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured in a cohort of 598 RTR. Cox regression analyses were used to analyze the association between vitamin C depletion (≤28 µmol/L; 22% of RTR) and mortality. Mediation analyses were performed according to Preacher and Hayes's procedure. At a median follow-up of 7.0 (6.2-7.5) years, 131 (21%) patients died. Vitamin C depletion was univariately associated with almost two-fold higher risk of mortality (Hazard ratio (HR) 1.95; 95% confidence interval (95%CI) 1.35-2.81, p < 0.001). This association remained independent of potential confounders (HR 1.74; 95%CI 1.18-2.57, p = 0.005). Hs-CRP, sICAM-1, sVCAM-1 and a composite score of inflammatory biomarkers mediated 16, 17, 15, and 32% of the association, respectively. Vitamin C depletion is frequent and independently associated with almost two-fold higher risk of mortality in RTR. It may be hypothesized that the beneficial effect of vitamin C at least partly occurs through decreasing inflammation.

Keywords: hs-CRP; inflammation; mortality; renal transplant; vitamin C.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure A1
Figure A1
Mediation analysis of combined score between hs-CRP, sICAM-1 and sVCAM-1 on the association of plasma vitamin C concentration with all-cause mortality. a, b and c are the standardized regression coefficients between variables. The indirect effect (through a potential mediator) is calculated as a × b. Total effect (c) is a × b + c’. Magnitude of mediation is calculated as indirect effect divided by total effect.
Figure 1
Figure 1
Kaplan-Meier curve for all-cause mortality according to plasma vitamin C status (depleted versus non-depleted) among renal transplant recipients. Vitamin C depleted: ≤28 µmol/L; Vitamin C non-depleted: >28 µmol/L.
Figure 2
Figure 2
Association of plasma vitamin C with risk of all-cause mortality. The line in the graph represents the hazard ratio. The grey area represents the 95% confidence interval of the hazard ratio.

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