A Reduction of Calcineurin Inhibitors May Improve Survival in Patients with De Novo Colorectal Cancer after Liver Transplantation

Saidy, Ramin Raul Ossami; Wegener, Elisa; Uluk, Deniz; Dittrich, Luca; Schöning, Wenzel; Lurje, Georg; Öllinger, Robert; Modest, Dominik Paul; Tacke, Frank; Haase, Oliver; Pratschke, Johann; Eurich, Dennis

doi:10.3390/medicina58121755

Cited by 2 publications

(2 citation statements)

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“…Currently, monitoring of immunosuppression is mainly based on measuring calcineurin inhibitor trough levels, but acute rejection can occur even if trough levels are within the target range (6). Previously, Vasudev et al introduced a semi-quantitative immunosuppression (IS) scale to assess the immunosuppressive burden in KTRs (7), which has been adopted and validated by various groups in different immunocompromised cohorts (8)(9)(10)(11). However, as the IS scale is calculated using simply the dosages of immunosuppressive medication, it fails to address the high inter-and intrapatient variability in the dosage required to reach certain trough levels of immunosuppressive agents such as tacrolimus (12,13).…”

Section: Introductionmentioning

confidence: 99%

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

Reineke,

Morath,

Speer

et al. 2024

Front. Med.

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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 × 107 c/mL) compared with those biopsied within 30 days (N = 20, median 7.35 × 103 c/mL) and > 1 year post-transplantation (N = 65, median 1.41 × 104 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.

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Section: Introductionmentioning

confidence: 99%

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

Reineke,

Morath,

Speer

et al. 2024

Front. Med.

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show abstract

“…For instance, the study of patients’ clinical course after the diagnosis of de novo CRC after liver transplantation, with an emphasis on the influence of immunosuppressive management, showed a significantly enhanced survival rate when the immunosuppressive therapy was reduced in an individualized manner, leading to an optimal oncological therapy and higher survival rates [ 10 ].…”

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confidence: 99%