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. 2023 Feb 10;12(2):454.
doi: 10.3390/antiox12020454.

Plasma Copper Concentration Is Associated with Cardiovascular Mortality in Male Kidney Transplant Recipients

Manuela Yepes-Calderón  1 , Daan Kremer  1 , Adrian Post  1 , Camilo G Sotomayor  1   2 , Ulrike Seidel  3 , Patricia Huebbe  3 , Tim J Knobbe  1 , Kai Lüersen  3 , Michele F Eisenga  1 , Eva Corpeleijn  4 , Martin H De Borst  1 , Gerjan J Navis  1 , Gerald Rimbach  3 , Stephan J L Bakker  1
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Plasma Copper Concentration Is Associated with Cardiovascular Mortality in Male Kidney Transplant Recipients

Manuela Yepes-Calderón et al. Antioxidants (Basel). .

Abstract

Kidney transplant recipients (KTR) are at increased risk of cardiovascular mortality. We investigated whether, in KTR, post-transplantation copper status is associated with the risk of cardiovascular mortality and potential effect modification by sex. In this cohort study, plasma copper was measured using mass spectrometry in extensively-phenotyped KTR with a functioning allograft >1-year. Cox regression analyses with the inclusion of multiplicative interaction terms were performed. In 660 KTR (53 ± 13 years old, 56% male), the median baseline plasma copper was 15.42 (IQR 13.53-17.63) µmol/L. During a median follow-up of 5 years, 141 KTR died, 53 (38%) due to cardiovascular causes. Higher plasma copper was associated with an increased risk of cardiovascular mortality in the overall KTR population (HR 1.37; 95% CI, 1.07-1.77 per 1-SD, p = 0.01). Sex was a significant effect modifier of this association (Pinteraction = 0.01). Among male KTR, higher plasma copper concentration was independently associated with a two-fold higher risk of cardiovascular mortality (HR 2.09; 95% CI, 1.42-3.07 per 1-SD, p < 0.001). Among female KTR, this association was absent. This evidence offers a rationale for considering a sex-specific assessment of copper's role in cardiovascular risk evaluation. Further studies are warranted to elucidate whether copper-targeted interventions may decrease cardiovascular mortality in male KTR.

Keywords: cardiovascular; copper; kidney transplantation; mortality.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Sex-stratified plasma copper concentration in KTR. Median plasma copper concentration was 14.64 [12.75–16.37] µmol/L for male KTR and 16.68 [14.64–19.20] µmol/L for female KTR. Plasma copper concentration was significantly different among males and females according to the Mann-Witney U test (p < 0.001). KTR, kidney transplant recipients.
Figure 2
Figure 2
Sex-stratified analyses of the associations between plasma copper concentration and cardiovascular mortality in KTR. Male (A) and female (B) KTR data were fitted using a cubic spline-based Cox proportional-hazards regression model. The reference value was the median plasma copper concentration of 14.64 µmol/L for males (A), and 16.68 µmol/L for females (B). The solid line represents the hazard ratio. The grey area represents the 95% confidence interval. KTR, kidney transplant recipients.
Figure 3
Figure 3
Association between plasma copper concentration and cardiovascular risk factors in KTR. Linear regression analyses among the overall KTR and among subgroups were performed. All variables were transformed to their natural logarithm. KTR, kidney transplant recipients; Std, standardized; LDL, low-density lipoprotein; hs-CRP, high-sensitivity C-reactive protein; ln, natural logarithm.
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References

    1. Tonelli M., Wiebe N., Knoll G., Bello A., Browne S., Jadhav D., Klarenbach S., Gill J. Systematic Review: Kidney Transplantation Compared with Dialysis in Clinically Relevant Outcomes. Am. J. Transplant. 2011;11:2093–2109. doi: 10.1111/j.1600-6143.2011.03686.x. - DOI - PubMed
    1. Gaston R.S., Fieberg A., Helgeson E.S., Eversull J., Hunsicker L., Kasiske B.L., Leduc R., Rush D., Matas A.J. Late Graft Loss After Kidney Transplantation: Is “Death with Function” Really Death with a Functioning Allograft? Transplantation. 2020;104:1483–1490. doi: 10.1097/TP.0000000000002961. - DOI - PubMed
    1. Wyld M.L.R., de La Mata N.L., Masson P., O’Lone E., Kelly P.J., Webster A.C. Cardiac Mortality in Kidney Transplant Patients: A Population-Based Cohort Study 1988–2013 in Australia and New Zealand. Transplantation. 2021;105:413–422. doi: 10.1097/TP.0000000000003224. - DOI - PubMed
    1. Rangaswami J., Mathew R.O., Parasuraman R., Tantisattamo E., Lubetzky M., Rao S., Yaqub M.S., Birdwell K.A., Bennett W., Dalal P., et al. Cardiovascular Disease in the Kidney Transplant Recipient: Epidemiology, Diagnosis and Management Strategies. Nephrol. Dial. Transplant. 2019;34:760–773. doi: 10.1093/ndt/gfz053. - DOI - PubMed
    1. Wilk A., Szypulska-Koziarska D., Marchelek-Myśliwiec M., Głazek W., Wiszniewska B. Serum Selenium, Iron, Zinc, and Copper Concentrations in Renal Transplant Recipients Treated with Mycophenolate Mofetil. Biol. Trace. Elem. Res. 2020;198:371–379. doi: 10.1007/s12011-020-02074-2. - DOI - PMC - PubMed

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