Evaluation of Torque Teno Virus DNA Load as a Predictive Biomarker in Kidney Transplant Recipients Converted from Calcineurin Inhibitors to Belatacept

Cabezas, Lara; Truffot, Aurelie; Germi, Raphaele; Bugnazet, Mathilde; Malvezzi, Paolo; Gnesotto, Manon; Rostaing, Lionel; Jouve, Thomas; Noble, Johan

doi:10.1016/j.ekir.2024.03.006

Kidney International Reports

2024

DOI: 10.1016/j.ekir.2024.03.006

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Evaluation of Torque Teno Virus DNA Load as a Predictive Biomarker in Kidney Transplant Recipients Converted from Calcineurin Inhibitors to Belatacept

Lara Cabezas,

Aurelie Truffot,

Raphaele Germi

et al.

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2024

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Cited by 3 publications

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“…In this respect, the most recent study on this topic conducted by Cabezas et al. , 9 which was published in the current issue of Kidney International Reports, is highly appreciated. Their major finding was that, conversion from a CNI-based or mTORi-based dual or triple immunosuppressive regimen to a belatacept-based dual or triple regimen did not affect TTV load.…”

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confidence: 95%

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Torque Teno Virus-Guided Immunosuppression in Kidney Transplantation: Expanding the Application

Eskandary,

Bond,

Mohan

2024

Kidney International Reports

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mentioning

confidence: 95%

“…, 5 the current study by Cabezas et al. 9 included more patients, followed the patients longitudinally, and was specifically designed to analyze TTV kinetics following conversion to belatacept. Taken together, the current literature does not support the hypothesis that TTV control is directly reduced due to costimulation blockade.…”

mentioning

confidence: 99%

Torque Teno Virus-Guided Immunosuppression in Kidney Transplantation: Expanding the Application

Eskandary,

Bond,

Mohan

2024

Kidney International Reports

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

Bredewold,

Moest,

de Fijter

et al. 2024

Journal of Medical Virology

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Torque 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.

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Torque Teno Virus Loads as a Marker of Immunosuppression in Pediatric Kidney Transplant Recipients

Kelly,

Awan,

Sweeney

et al. 2024

Pediatric Transplantation

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BackgroundLong‐term renal function and survival after kidney transplantation rely on appropriate immunosuppressive treatment to prevent the risk of rejection. New biomarkers are needed to accurately assess the degree of immunosuppression in renal transplant recipients in order to avoid organ rejection and the development of opportunistic infections. Highly prevalent in humans, torque teno virus (TTV), which belongs to the family Anelloviridae, is a small, nonenveloped, single‐stranded DNA virus which has not been linked with any specific human illness, but which constitutes a major component of the human virome. Host antiviral responses allow TTV levels to be controlled; however, viral persistence remains, explaining the high prevalence in human populations, including healthy individuals. Important confounders of TTV load include time since transplantation, age, gender, obesity, and smoking status.AimsTTV‐based guidance of immunosuppressive drug dosing could help with risk stratification, reducing the risk of infection, graft rejection and oncologic disease on an individual level, enabling long‐term patient and graft survival.MethodsOriginal studies were accessed by a systematic search from electronic databases including PubMed, ScienceDirect and Wiley Online Library.ResultsThe presented data mainly derive from adult transplant recipients showing an association between TTV plasma levels and the immune status of the host: High‐TTV load and high immunosuppression are associated with a risk of infection, and low‐TTV load and low immunosuppression indicate a risk of rejection. However, there is minimal information on pediatric transplant recipients with further research required in this cohort. To date, it has been demonstrated that longer posttransplant times are significantly associated with lower TTV levels in children with renal transplant. Meanwhile, an association between lower TTV loads and increased risk of graft reject during the first year of transplantation was also reported. More recently, Eibensteiner et al. revealed a robust, independent association between TTV plasma load and the onset of Cytomegalovirus and BK virus infections.ConclusionData from randomized controlled trials are still missing, even in adults, but a multicenter randomized controlled trial for TTV‐guided immunosuppression in adult kidney recipients (TTVguideIT) began in 2022. There is, therefore, great promise for TTV levels to be used as a biomarker that could potentially improve both graft and patient survival in transplantation.

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Evaluation of Torque Teno Virus DNA Load as a Predictive Biomarker in Kidney Transplant Recipients Converted from Calcineurin Inhibitors to Belatacept

Cited by 3 publications

References 33 publications

Torque Teno Virus-Guided Immunosuppression in Kidney Transplantation: Expanding the Application

Torque Teno Virus-Guided Immunosuppression in Kidney Transplantation: Expanding the Application

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

Torque Teno Virus Loads as a Marker of Immunosuppression in Pediatric Kidney Transplant Recipients

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