Dynamics of torque teno virus load in kidney transplant recipients with indication biopsy and therapeutic modifications of immunosuppression.

Autor:	Reineke M; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany., Morath C; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany.; German Center for Infection Research, DZIF, Heidelberg Partner Site, Heidelberg, Germany., Speer C; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany.; Department of Molecular Medicine Partnership Unit Heidelberg, European Molecular Biology Laboratory, Heidelberg, Germany., Rudek M; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany., Bundschuh C; Medical Faculty Heidelberg, Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg, Germany., Klein JAF; Medical Faculty Heidelberg, Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg, Germany., Mahler CF; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany., Kälble F; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany., Nusshag C; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany., Beimler J; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany., Zeier M; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany., Bartenschlager R; German Center for Infection Research, DZIF, Heidelberg Partner Site, Heidelberg, Germany.; Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Diseases Research, Heidelberg University, Heidelberg, Germany.; Division Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, Germany., Schnitzler P; German Center for Infection Research, DZIF, Heidelberg Partner Site, Heidelberg, Germany.; Medical Faculty Heidelberg, Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg, Germany., Benning L; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2024 Jan 24; Vol. 11, pp. 1337367. Date of Electronic Publication: 2024 Jan 24 (Print Publication: 2024).
DOI:	10.3389/fmed.2024.1337367
Abstrakt:	Following kidney transplantation, lifelong immunosuppressive therapy is essential to prevent graft rejection. On the downside, immunosuppression increases the risk of severe infections, a major cause of death among kidney transplant recipients (KTRs). To improve post-transplant outcomes, adequate immunosuppressive therapy is therefore a challenging but vital aspect of clinical practice. Torque teno virus load (TTVL) was shown to reflect immune competence in KTRs, with low TTVL linked to an elevated risk for rejections and high TTVL associated with infections in the first year post-transplantation. Yet, little is known about the dynamics of TTVL after the first year following transplantation and how TTVL changes with respect to short-term modifications in immunosuppressive therapy. Therefore, we quantified TTVL in 106 KTRs with 108 clinically indicated biopsies, including 65 biopsies performed >12 months post-transplantation, and correlated TTVL to histopathology. In addition, TTVL was quantified at 7, 30, and 90 days post-biopsy to evaluate how TTVL was affected by changes in immunosuppression resulting from interventions based on histopathological reporting. TTVL was highest in patients biopsied between 1 and 12 months post-transplantation (N = 23, median 2.98 × 10 ⁷ c/mL) compared with those biopsied within 30 days (N = 20, median 7.35 × 10 ³ c/mL) and > 1 year post-transplantation (N = 65, median 1.41 × 10 ⁴ c/mL; p < 0.001 for both). Patients with BK virus-associated nephropathy (BKVAN) had significantly higher TTVL than patients with rejection ( p < 0.01) or other pathologies ( p < 0.001). When converted from mycophenolic acid to a mTOR inhibitor following the diagnosis of BKVAN, TTVL decreased significantly between biopsy and 30 and 90 days post-biopsy ( p < 0.01 for both). In KTR with high-dose corticosteroid pulse therapy for rejection, TTVL increased significantly between biopsy and 30 and 90 days post-biopsy ( p < 0.05 and p < 0.01, respectively). Of note, no significant changes were seen in TTVL within 7 days of changes in immunosuppressive therapy. Additionally, TTVL varied considerably with time since transplantation and among individuals, with a significant influence of age and BMI on TTVL ( p < 0.05 for all). In conclusion, our findings indicate that TTVL reflects changes in immunosuppressive therapy, even in the later stages of post-transplantation. To guide immunosuppressive therapy based on TTVL, one should consider inter- and intraindividual variations, as well as potential confounding factors. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Reineke, Morath, Speer, Rudek, Bundschuh, Klein, Mahler, Kälble, Nusshag, Beimler, Zeier, Bartenschlager, Schnitzler and Benning.)
Databáze:	MEDLINE
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