Virus-specific T cells in pediatric renal transplantation

Ahlenstiel-Grunow, Thurid; Pape, Lars

doi:10.1007/s00467-020-04522-6

Cited by 11 publications

(6 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, high IPV could be associated with increased calcineurin inhibitor nephrotoxicity even in low tacrolimus trough level regimens [34,35]. Transplant‐associated infections like CMV or BKV infection could also have an association with high IPV (several intervals of over‐immunosuppression) and poor graft survival [36,37]. Another point is that patients included in this study underwent kidney transplantation between 2001 and 2017.…”

Section: Discussionmentioning

confidence: 99%

Association of graft survival with tacrolimus exposure and late intra‐patient tacrolimus variability in pediatric and young adult renal transplant recipients—an international CTS registry analysis

et al. 2020

View full text Add to dashboard Cite

Summary Adolescent and young adult age is a high‐risk window with an alarmingly increased likelihood of premature kidney graft loss due to immunological rejection. Using the large database of the Collaborative Transplant Study, we analyzed whether a more intense and less variable exposure to tacrolimus could counteract this young age‐related enhanced immunoreactivity. Kidney graft recipients aged 12–23 years (n = 964) with a 1‐year tacrolimus trough level between 4.0 and 10.9 ng/ml had a 5‐year graft survival rate of 85.1%, significantly better than the poor 66.1% rate in patients with a trough level below 4.0 ng/ml who showed a 2.38‐fold increased risk of graft loss in the multivariable analysis (P < 0.001). This association was not apparent in young children aged 0–11 years (n = 455) and less pronounced in adults aged 24–34 years (n = 1466). However, an intra‐patient variability of tacrolimus (IPV) trough level ≥1.5 at post‐transplant years 1 and 2 was associated with an increased graft loss risk in both 12‐ to 23‐year‐old and 0‐ to 11‐year‐old recipients (P < 0.001 and P = 0.045). Patients with high IPV made up as many as 30% of kidney graft recipients, indicating that a more intense and less variable exposure to tacrolimus could improve graft survival strongly in this high‐risk group.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of graft survival with tacrolimus exposure and late intra‐patient tacrolimus variability in pediatric and young adult renal transplant recipients—an international CTS registry analysis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Besides, there is increasing evidence that Tvis mirror not only the virusspecific but also the general cellular immune defense. Thus, Tvis may serve as a marker to identify overimmunosuppression [36][37][38].…”

Section: Virus-specific T Cells As a Promising Biomarkermentioning

confidence: 99%

“…Also in children, it has been shown that the number of Tvis is associated with the risk of virus diseases [ 30 – 33 ]. Regarding the high incidence of post-transplant viral complications (especially in children), prophylaxis, diagnosis, and treatment of viral infections may be improved by the inclusion of Tvis-analysis in routine monitoring after kidney transplantation [ 36 , 37 ]. Besides, there is increasing evidence that Tvis mirror not only the virus-specific but also the general cellular immune defense.…”

Section: Innovative Non-cellular Biomarkersmentioning

confidence: 99%

Novel ways to monitor immunosuppression in pediatric kidney transplant recipients—underlying concepts and emerging data

Ahlenstiel-Grunow

Pape

2021

Mol Cell Pediatr

Self Cite

View full text Add to dashboard Cite

After pediatric kidney transplantation, immunosuppressive therapy is given to avoid acute and chronic rejections. However, the immunosuppression causes an increased risk of severe viral complications and bacterial infections and is associated with serious side effects. It is therefore crucial to achieve the optimal individual balance between over- and under-immunosuppression and thereby avoid unnecessary exposure to immunosuppressive drugs. In routine use, steering of immunosuppressants is performed primarily by monitoring of trough levels that mirror pharmacokinetics (although not, however, pharmacodynamics). Other diagnostic and prognostic markers to assess the individual intensity of immunosuppression are missing. Potential methods to determine immune function and grade of immunosuppression, such as analysis of the torque teno virus (TTV) load, QuantiFERON Monitor®, and ImmuKnow® as well as virus-specific T cells (Tvis), are currently being evaluated. In some studies TTV load, QuantiFERON Monitor® and ImmuKnow® were associated with the risk for post-transplant rejections and infections, but randomized controlled trials after pediatric kidney transplantation are not available. Post-transplant monitoring of Tvis levels seem to be promising because Tvis control virus replication and have been shown to correlate with virus-specific as well as general cellular immune defense, which represents the individual’s susceptibility to infections. Additional Tvis-monitoring provides an innovative opportunity to personalize the antiviral management and the dosing of the immunosuppressive therapy after pediatric kidney transplantation to avoid unnecessary therapeutic interventions and identify over-immunosuppression.

show abstract

“…Other markers, such as the "ImmuKnow" assay 22 or the measurement of Torque-Teno virus load, 9 have been evaluated retrospectively in this regard with variable results, but they have never been used in a prospective trial. Previously, Tvis measurements have been shown to improve management of post-transplant viral infections (for example, in CMV 10,23 or BK polyomavirus infection 11,13,14 ), but the value as a diagnostic marker of overimmunosuppression has not been hitherto assessed.…”

Section: Discussionmentioning

confidence: 99%

“…10 Accordingly, they may serve as an indicator of the intensity of immunosuppression as well as a prognostic marker for virus-induced diseases after transplantation. [10][11][12][13][14] The randomized IVIST trial has been designed to investigate the hypothesis that additional steering of immunosuppressive therapy by Tvis levels optimizes dosing of immunosuppressive therapy 15 (effect-related drug monitoring), resulting in a personalized treatment with improved clinical courses on the basis of fewer viral infections and possible changes in exposure to immunosuppressive drugs.…”

mentioning

confidence: 99%

Steering Transplant Immunosuppression by Measuring Virus-Specific T Cell Levels: The Randomized, Controlled IVIST Trial

Ahlenstiel-Grunow

Liu

Schild

et al. 2020

JASN

Self Cite

View full text Add to dashboard Cite

Background Pharmacokinetic monitoring is insufficient to estimate the intensity of immunosuppression after transplantation. Virus-specific T cells correlate with both virus-specific and general cellular immune defense. Additional steering of immunosuppressive therapy by virus-specific T cell levels might optimize dosing of immunosuppressants. Methods In a multicenter, randomized, controlled trial, we randomized 64 pediatric kidney recipients to a control group with trough-level monitoring of immunosuppressants or to an intervention group with additional steering of immunosuppressive therapy by levels of virus-specific T cells (quantified by cytokine flow cytometry). Both groups received immunosuppression with cyclosporin A and everolimus in the same target range of trough levels. Primary end point was eGFR 2 years after transplantation. Results In the primary analysis, we detected no difference in eGFR for the intervention and control groups 2 years after transplantation, although baseline eGFR 1 month after transplantation was lower in the intervention group versus the control group. Compared with controls, patients in the intervention group received significantly lower daily doses of everolimus and nonsignificantly lower doses of cyclosporin A, resulting in significantly lower trough levels of everolimus (3.5 versus 4.5 µg/L, P<0.001) and cyclosporin A (47.4 versus 64.1 µg/L, P<0.001). Only 20% of patients in the intervention group versus 47% in the control group received glucocorticoids 2 years after transplantation (P=0.04). The groups had similar numbers of donor-specific antibodies and serious adverse events. Conclusions Steering immunosuppressive therapy by virus-specific T cell levels in addition to pharmacokinetic monitoring seems safe, results in a similar eGFR, and personalizes immunosuppressive therapy by lowering exposure to immunosuppressive drugs, likely resulting in lower drug costs. Clinical Trial registry name and registration number: IVIST trial, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2009-012436-32 and ISRNCT89806912

show abstract

Virus-specific T cells in pediatric renal transplantation

Cited by 11 publications

References 71 publications

Association of graft survival with tacrolimus exposure and late intra‐patient tacrolimus variability in pediatric and young adult renal transplant recipients—an international CTS registry analysis

Association of graft survival with tacrolimus exposure and late intra‐patient tacrolimus variability in pediatric and young adult renal transplant recipients—an international CTS registry analysis

Novel ways to monitor immunosuppression in pediatric kidney transplant recipients—underlying concepts and emerging data

Steering Transplant Immunosuppression by Measuring Virus-Specific T Cell Levels: The Randomized, Controlled IVIST Trial

Contact Info

Product

Resources

About