June 8, 2026
An international research team has demonstrated in a clinical trial that TTV-guided dosing of immunosuppressive drugs in kidney transplant recipients is safe. The results of the study, presented at the annual congress of the European Society of Nephrology, suggest that immunosuppressive therapy could be further personalised and reduced in certain patient groups in the future. The LUMC, in particular professors Joris Rotmans, Aiko de Vries (NIER/TRAX), and Mariet Feltkamp (LUCID), and PhD students Aline van Rijn (LUCID) and Wouter Moest (NIER) made a substantial contribution to this study, part of the EU project TTVguideTX.
Following a kidney transplant, patients must take medication that suppresses the immune system on a long-term basis. Immunosuppression protects the transplanted organ from rejection. However, if too strong, the risk of infection increases; if too weak, it can lead to damage or loss of the organ, for instance by infection. To date, dosing has usually been controlled based on target drug levels in the blood. However, these values provide only limited insight into how strongly an individual’s immune system is actually suppressed.
The trial investigated whether TTV could serve as a biomarker to help manage immunosuppression more individually. TTV is present in many people, does not cause disease, and mirrors activity of the immune system: low TTV loads may indicate an (over)active immune system, whilst high loads may indicate an underactive immune system. The aim was to adjust immunosuppression not only according to fixed drug levels, but to align it more closely with the transplant patients’ actual immunological status.
260 patients across 6 European countries
The randomised, controlled phase II study, conducted at 13 academic centres in Austria, Germany, France, the Czech Republic, Spain and the Netherlands, included 260 adult kidney transplant recipients. TTV-loads were measured by qPCR every month. Four months after transplantation, patients were randomised to either TTV-guided tacrolimus dosing, or standard treatment. The primary endpoint comprised infections, graft rejection, graft loss or death. In the TTV-guided group, this composite endpoint occurred in 35% of patients, compared with 38% in the control group. The study thus achieved its objective of demonstrating the non-inferiority of TTV-guided dosing compared with standard treatment. At the same time, patients in the TTV-guided group had lower tacrolimus levels and received lower daily doses. A statistically significant reduction in infections was not demonstrated, however, the results suggest that in stable, low-risk patients, reduced immunosuppression may be possible without compromising the safety of the transplanted organ.
Scientifically, the study marks several steps into a new field: it is the first study in which immunosuppression following organ transplantation was controlled using a biomarker, and the first multicentre biomarker study in the field of organ transplantation to achieve its primary endpoint. A follow-up multicentre study is currently underway in France investigating the TTV-guided approach in patients from the second year post-transplant onwards. Other studies like the EU project SQUEEZE, in which LUCID and REUM participate, will show if there is added value of TTV-guidance in the treatment of rheumatoid arthritis.
Publications
Bredewold OW, Moest WT, de Fijter JW, Meijers E, Bruchfeld A, Skov K, Svensson MHS, Chan J, Mjornstedt L, Sorensen SS, Fellstrom B, Feltkamp MCW, van Zonneveld AJ, Rotmans JI. Attenuation of Torque teno viral load over time in kidney transplantation recipients treated with calcineurin inhibitors is mitigated after conversion to belatacept. J Med Virol. 2024 Sep;96(9):e29905. doi: 10.1002/jmv.29905. PMID: 39228322
Van Rijn AL, Roos R, Dekker FW, Rotmans JI, Feltkamp M. Torque teno virus load as marker of rejection and infection in solid organ transplantation - A systematic review and meta-analysis. Rev Med Virol. 2023 Jan;33(1):e2393. doi: 10.1002/rmv.2393. Epub 2022 Sep 3. PMID: 36056751
Van Rijn AL, Wunderink HF, Sidorov IA, de Brouwer CS, Kroes AC, Putter H, de Vries AP, Rotmans JI, Feltkamp MC. Torque teno virus loads after kidney transplantation predict allograft rejection but not viral infection. J Clin Virol. 2021 Jul;140:104871. doi: 10.1016/j.jcv.2021.104871. Epub 2021 May 25. PMID: 34089977
