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Mortality from cancer is not increased in elderly kidney transplant recipients compared to the general population: a competing risk analysis

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Abstract

Background

The impact of cancer on death of elderly kidney transplant recipients has been extensively investigated, but with conflicting results. Unlike their younger counterparts, in elderly kidney transplant recipients cardiovascular and infectious disease may outweigh cancer in causing the patient’s death.

Methods

Using competing risk analysis on a large retrospective cohort of kidney transplant recipients, we estimated the cause-specific cumulative incidence and hazard of death in different age categories and calculated standardized mortality ratios (SMRs) to compare mortality rates with the general population.

Results

Six thousand seven hundred eighty-nine kidney transplant recipients were followed-up for a median of 9 years. Ten years after transplantation, in transplant recipients aged 20–39, 40–59, and 60+, the cumulative incidence of cancer-related death was 0.6 (95% confidence interval [CI]: 0.3–1.0), 2.9 (2.3–3.6) and 5.3% (3.5–7.5), whereas the SMR was 9.1 (5.5–15.0), 2.0 (1.6–2.5), and 0.8 (0.6–1.0), respectively. At variance with young recipients, the hazard and the cumulative incidence of cardiovascular-related death in elderly recipients was well above that of cancer-related death.

Conclusions

Relative to the general population, cancer-related death is increased in young but not in elderly kidney transplant recipients because of the more marked increased incidence of competing cause of death in the latter category.

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Acknowledgements

We gratefully acknowledge Dr. Emanuele Crocetti and Dr. Stefano Ferretti from the AIRTUM, for having provided mortality rates of cancer in the general Italian population, and Dr. Matteo Malvezzi from the Mario Negri Institute of Pharmacological Research of Milano, for having provided mortality rates of squamous cell carcinoma of the skin in the general Italian population.

Funding

None.

Author information

Author notes

  1. Gianpaolo Tessari and Umberto Maggiore contributed equally to the manuscript.

Authors and Affiliations

  1. Section of Dermatology, Dermatology Unit, Department of Medicine, University of Verona, Ospedale Civile Maggiore, Piazzale Stefani 1, 37126, Verona, VR, Italy

    Gianpaolo Tessari & Giampiero Girolomoni

  2. Nephrology Unit, Dipartimento di Medicina e Chirurgia, Università di Parma, Azienda-Ospedaliero Universitaria di Parma, Parma, Italy

    Umberto Maggiore & Alessandra Palmisano

  3. Nephrology Unit, Department of Medicine, University of Verona, Verona, Italy

    Gianluigi Zaza

  4. Kidney Transplantation Centre, Azienda Ospedaliero Universitaria Integrata, Verona, Italy

    Rostand Emmanuel Nguefouet Momo, Francesco Nacchia & Luigino Boschiero

  5. Nephrology Unit, Azienda Ospedaliera Spedali Civili, Brescia, Italy

    Silvio Sandrini

  6. Dermatology Unit, Ospedale San Bortolo, Azienda Ospedaliera Vicenza, Vicenza, Italy

    Luigi Naldi

  7. Nephrology Unit, Ospedali Riuniti, Bergamo, Italy

    Eliana Gotti

  8. Nephrology Unit, Ospedale Maggiore-Policlinico, MaRE, IRCCS, Milan, Italy

    Mariarosaria Campise & Piergiorgio Messa

  9. Department of Nephrology, Dialysis and Renal Transplantation, S. Orsola University Hospital, Bologna, Italy

    Irene Capelli

  10. Nephrology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

    Enrico Minetti

  11. Nephrology Unit, Azienda Ospedaliero Universitaria Consorziale Policlinico, Bari, Italy

    Michele Rossini

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  1. Gianpaolo Tessari
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  2. Umberto Maggiore
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  3. Gianluigi Zaza
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  5. Francesco Nacchia
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Contributions

GT, UM, GZ and GG participated in research design, the writing of the paper, in the performance of the research and in data analysis. GT and UM contributed equally. RENM, LN, LB, FN, SS, EG, MC, PM, AP, IC, EM and MR participated in research design, in the performance of the research and revising the manuscript.

Corresponding author

Correspondence to Gianpaolo Tessari.

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Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest. No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research, that has not been published previously, and is not under consideration for publication elsewhere, in whole or in part. And all the authors listed have approved the manuscript that is enclosed.

Ethical statement

All subjects were treated with standard care without intervention from this study. All data were obtained via electronic medical records and a database review and were de-identified (the patient’s name was replaced with an identification code, and the patient’s private information was deleted before the analysis) to protect patient privacy.

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Electronic supplementary material

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40620_2020_847_MOESM1_ESM.pptx

Supplementary file1Figure S1. Sub-hazard ratios (SHRs) of death from each specific cause as predicted by the fitted multiple regression model of Fine and Gray for competing risk. Calendar year was fitted as a polynomial continuous variate. The reference value of SHR (i.e. SHR=1) was represented by age 40-59 and calendar year 2000. Dots do not represent SHRs of groups of actual patients but rather predicted SHR values of hypothetical patients in the selected age category and calendar year: the plot is meant to have a visual appraisal of the SHR estimates from an otherwise complex multiple regression model. Both calendar year and age category were statistically significant (P<0.001). SHR, Sub-hazard ratio (i.e. the ratio between hazards which are calculated including patients who already died from other causes to reflect the hazards the actually the observed cumulative incidences of CVD-related death in the presence of competing causes of death). Figure S2. Sub-hazard ratios (SHRs) of death from each specific cause as predicted by the fitted multiple regression model of Fine and Gray for competing risk. Calendar year was fitted as a polynomial continuous variate. The reference value of SHR (i.e. SHR=1) was represented by age 40-59 and calendar year 2000. Dots do not represent SHRs of groups of actual patients but rather predicted SHR values of hypothetical patients in the selected age category and calendar year: the plot is meant to have a visual appraisal of the SHR estimates from an otherwise complex multiple regression model. Both calendar year and age category were statistically significant (P<0.001); in addition, the interaction term between age category and polynomial calendar year was significant (P<0.001) meaning that the SHR did not consistently increase with age categories in all historical periods. SHR, Sub-hazard ratio (i.e. the ratio between hazards which are calculated including patients who already died from other causes to reflect the hazards the actually the observed cumulative incidences of cancer-related death in the presence of competing causes of death) (PPTX 206 kb)

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Tessari, G., Maggiore, U., Zaza, G. et al. Mortality from cancer is not increased in elderly kidney transplant recipients compared to the general population: a competing risk analysis. J Nephrol 33, 1309–1319 (2020). https://doi.org/10.1007/s40620-020-00847-5

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