Induction Therapy With Antithymocyte Globulin and Delayed Calcineurin Inhibitor Initiation for Renal Protection in Liver Transplantation: A Multicenter Randomized Controlled Phase II-B Trial
| Autor: | Shimul A. Shah, Tiffany L Kaiser, Jessica Bollinger, Kazunari Sasaki, Xaralambos Zervos, Federico Aucejo, Laia Coromina Hernandez, Koji Hashimoto, Amit Nair, John J. Fung, Masato Fujiki, Charles M. Miller, Cristiano Quintini, Bijan Eghtesad, Michael A. Zimmerman, Teresa Diago |
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| Rok vydání: | 2021 |
| Předmět: |
Graft Rejection
medicine.medical_specialty medicine.medical_treatment Calcineurin Inhibitors Urology Renal function Liver transplantation Kidney Tacrolimus chemistry.chemical_compound medicine Clinical endpoint Humans Antilymphocyte Serum Transplantation Creatinine business.industry Immunosuppression Induction Chemotherapy Perioperative Kidney Transplantation Liver Transplantation Calcineurin chemistry business Immunosuppressive Agents |
| Zdroj: | Transplantation. 106:997-1003 |
| ISSN: | 0041-1337 |
| Popis: | Background Calcineurin inhibitor (CNI) based immunosuppression in liver transplantation (LTx) is associated with acute and chronic deterioration of kidney function. Delaying CNI initiation by using induction rabbit anti-thymocyte globulin (rATG) may provide kidneys with adequate time to recover from a perioperative insult reducing the risk of early post-LTx renal deterioration. Methods This was an open-label, multicenter, randomized controlled clinical trial comparing use of induction rATG with delayed CNI initiation (day-10) against upfront CNI commencement (SOC; standard of care) in those patients deemed at standard risk of postoperative renal dysfunction following LTx. The primary end point was change in (delta) creatinine from baseline to month-12. Results Fifty-five patients were enrolled in each study arm. Mean Tacrolimus levels remained comparable in both groups from day-10 throughout the study period. A significant difference in delta creatinine was observed between rATG and SOC groups at 9-months (p=0.03) but not at month-12 (p=0.05). eGFR levels remained comparable between cohorts at all time points. Rates of biopsy-proven acute rejection at 1-year were similar between groups (16.3 vs 12.7%, p= 0.58). rATG showed no significant adverse effects. Survival at 12-months was comparable between groups (p= 0.48). Conclusions Although the use of induction rATG and concurrent CNI deferral in this study did not demonstrate a significant difference in delta creatinine at 1 year, these results indicate a potential role for rATG in preserving early kidney function, especially when considered with CNI deferral beyond 10 days and/or lower target Tacrolimus levels, with acceptable safety and treatment efficacy. |
| Databáze: | OpenAIRE |
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