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Causes of late transplant failure in cyclosporine-treated kidney allograft recipients

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Abstract

Background

There is little information about very long-term outcomes of kidney allograft recipients exposed to calcineurin inhibitors.

Methods

In this single-centre retrospective study with 20-year follow-up, we analyzed data from 644 patients who underwent primary renal transplantation between 1983 and 1993. Participants were treated with a cyclosporine-based immunosuppressive scheme and had allograft function at 1 year.

Results

After 20 years, 15.2% patients died, 39.7% experienced allograft loss, 26.8% were alive with a functioning transplant, and 18.2% were lost to follow-up. Cardiovascular disease (30.8%), malignancy (26.6%) and infection (17.0%) were the main causes of death. Age, new-onset proteinuria > 1 g/day, major acute cardiovascular event (MACE), and malignancy were independent predictors of mortality at time-dependent multivariate analysis. Chronic rejection (63.3%), recurrent glomerulonephritis (14.0%), and nonspecific interstitial fibrosis/tubular atrophy (13.2%) were the leading cause of allograft loss. Basal disease, hepatitis C, difference between 1 year and nadir serum creatinine, new-onset proteinuria > 1 g/day, and MACE were independent predictors of transplant failure. Among patients with 20-year allograft function, we recorded the following complications: hypertension (85%), malignancy (13%), diabetes (9%), and cardiovascular disease (9%). Median serum creatinine and proteinuria were 1.4 mg/dL and 0.6 g/day, respectively.

Conclusions

Prolonged use of cyclosporine may expose to several dose-related adverse events and may contribute to the development of allograft dysfunction but it does not necessarily cause relentless, progressive transplant failure if patients are carefully and consistently monitored during the follow-up.

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Author information

Author notes

  1. Claudio Ponticelli and Piergiorgio Messa are the equally contributing senior authors.

Authors and Affiliations

  1. Nephrology and Dialysis, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Gabriella Moroni, Valentina Binda, Francesca Raffiotta, Francesco Cosa, Giuseppe Montagnino & Piergiorgio Messa

  2. Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy

    Silvana Quaglini & Lucia Sacchi

  3. Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via della Commenda 15, 20122, Milan, Italy

    Evaldo Favi

  4. Renal Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Claudio Ponticelli

Authors
  1. Gabriella Moroni
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  2. Valentina Binda
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  3. Silvana Quaglini
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  4. Lucia Sacchi
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  7. Giuseppe Montagnino
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  8. Evaldo Favi
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  10. Claudio Ponticelli
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Corresponding author

Correspondence to Evaldo Favi.

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Conflict of interest

The authors have declared that no conflict of interest exists.

Ethical approval

All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee at which the studies were conducted and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. At the time the study was designed, it was formally discussed in our regular Multidisciplinary Research Meeting at the Ospedale Maggiore Policlinico (Milan, Italy) and the consensus was that IRB approval was not necessary because it was retrospective and non-interventional. Therefore, nor specific IRB approval number nor specific written documents regarding the present study are actually available. All transplant recipients followed up at our institution are consented for both treatment and research purposes at the time of activation on the transplant waiting list as per local and national regulatory requirements. As a consequence, all subjects enrolled into the study were already aware that their anonymized data including viral status and other biomedical parameters would have been used for planning and/or research.

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Informed consent was obtained from all individual participants included in the study.

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Moroni, G., Binda, V., Quaglini, S. et al. Causes of late transplant failure in cyclosporine-treated kidney allograft recipients. Clin Exp Nephrol 23, 1076–1086 (2019). https://doi.org/10.1007/s10157-019-01740-7

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  • DOI: https://doi.org/10.1007/s10157-019-01740-7

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