Attenuation of Torque teno viral load over time in kidney transplantation recipients treated with calcineurin inhibitors is mitigated after conversion to belatacept

Author:

Bredewold O. W.1ORCID,Moest W. T.1ORCID,de Fijter J. W.12ORCID,Meijers E.3,Bruchfeld A.4ORCID,Skov K.5ORCID,Svensson M. H. S.56ORCID,Chan J.6ORCID,Mjornstedt L.7ORCID,Sorensen S. S.8ORCID,Fellstrom B.9ORCID,Feltkamp M. C. W.3ORCID,van Zonneveld A. J.1ORCID,Rotmans J. I.1ORCID

Affiliation:

1. Department of Internal Medicine (Nephrology) Leiden University Medical Center Leiden The Netherlands

2. Department of Nephrology Antwerp University Medical Center Edegem Belgium

3. Department of Medical Microbiology and Infection Control, Leiden University Center for Infectious diseases Leiden University Medical Center Leiden The Netherlands

4. Department of Health, Medicine and Caring Sciences Linköping University Linköping Sweden

5. Department of Renal Medicine Aarhus University Hospital Aarhus Denmark

6. Department of Nephrology Akershus University Hospital Lorenskog Norway

7. Transplantation Institute Sahlgrenska University Hospital Goteborg Sweden

8. Department of Nephrology, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

9. Department of Medical Science, Renal Unit University Hospital Uppsala Sweden

Abstract

AbstractTorque Teno Virus (TTV) is a non‐pathogenic anellovirus, highly prevalent in healthy populations. Variations in its viral load have been associated with states of diminished immunity, as occurs after organ transplantation. It is hypothesized that TTV‐load might be used as a diagnostic tool to guide prescription and dosing of immunosuppressive drugs. Not much is known about the effects of combined immunosuppressive drugs on TTV replication in renal transplantation. Belatacept was introduced to counter side‐effects of calcineurin inhibitors (CNI). It was never widely adopted, mainly because its association with increased risk of rejection. To investigate the differential effects of a regimen based on calcineurin inhibitors versus belatacept on TTV‐loads, we measured TTV‐levels in 105 patients from two randomized controlled trials in kidney transplant recipients (KTRs). We observed that time after transplantation was inversely related to TTV‐levels of patients that remained on a CNI‐containing regime, whereas this decline over time was diminished after conversion to belatacept. In addition, a correlation with tacrolimus‐trough levels and age were found. Our study is the first report on the impact of conversion from CNI to belatacept on TTV‐levels in KTR. In conclusion, the time‐related decline in TTV‐levels is mitigated after conversion from CNI to belatacept.

Funder

Horizon 2020 Framework Programme

Publisher

Wiley

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