Clinical Significance of the Cellular Pharmacodynamics of Tacrolimus in Living-Donor Liver Transplantation
Successful immunosuppressive therapy is critical for liver transplantation; however, a considerable number of patients experience fatal rejection or alternatively exhibit serious infection resulting from excessive immunosuppression. The in vitro tacrolimus response of peripheral blood mononuclear ce...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2009-05-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/096368970901805-622 |
| _version_ | 1818141863034486784 |
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| author | Abuduxukuer Mijiti Naoto Matsuno Hironori Takeuchi Sakae Unezaki Takeshi Nagao Toshihiko Hirano |
| author_facet | Abuduxukuer Mijiti Naoto Matsuno Hironori Takeuchi Sakae Unezaki Takeshi Nagao Toshihiko Hirano |
| author_sort | Abuduxukuer Mijiti |
| collection | DOAJ |
| description | Successful immunosuppressive therapy is critical for liver transplantation; however, a considerable number of patients experience fatal rejection or alternatively exhibit serious infection resulting from excessive immunosuppression. The in vitro tacrolimus response of peripheral blood mononuclear cells (PBMCs) before transplantation was compared to the clinical outcome up to 4 weeks after operation in 28 living-donor liver transplant recipients treated with tacrolimus. The tacrolimus IC 50 values against concanavalin A-induced PBMC blastogenesis in vitro were calculated. These recipients were classified into two groups with the mean tacrolimus IC 50 (0.18 ng/ml) as the cutoff point, after which the clinical outcome between the patient groups was compared. The allograft rejection incidence in the low-sensitivity group (IC 50 < 0.18 ng/ml; n = 16) was 6/12 (50.0%), which was significantly higher than the incidence of 2/16 (12.5%) in the high-sensitivity group (IC 50 > 0.18 ng/ml; n = 12) ( p = 0.0297). In contrast, the infection incidence in the high-sensitivity group was 6/16 (37.5%), which was significantly higher than that of the low-sensitivity group (1/12; 8.3%) ( p = 0.0401). These data suggest that patients exhibiting a low PBMC sensitivity to tacrolimus have a risk of rejection, whereas highly sensitive patients have a risk of infection in living-donor liver transplantations under tacrolimus therapy. |
| first_indexed | 2024-12-11T11:06:38Z |
| format | Article |
| id | doaj.art-303402ecf20f4baaa6c1e62749dad8fb |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-11T11:06:38Z |
| publishDate | 2009-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-303402ecf20f4baaa6c1e62749dad8fb2022-12-22T01:09:40ZengSAGE PublishingCell Transplantation0963-68971555-38922009-05-011810.1177/096368970901805-622Clinical Significance of the Cellular Pharmacodynamics of Tacrolimus in Living-Donor Liver TransplantationAbuduxukuer Mijiti0Naoto Matsuno1Hironori Takeuchi2Sakae Unezaki3Takeshi Nagao4Toshihiko Hirano5Department of Surgery, Kashgar First People's Hospital, Xinjiang Uyghur Autonomous Region, ChinaDepartment of 5th Surgery, Hachioji Medical Center, Tokyo Medical University, Tokyo 193-0944, JapanDepartment of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanDepartment of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanDepartment of 5th Surgery, Hachioji Medical Center, Tokyo Medical University, Tokyo 193-0944, JapanDepartment of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanSuccessful immunosuppressive therapy is critical for liver transplantation; however, a considerable number of patients experience fatal rejection or alternatively exhibit serious infection resulting from excessive immunosuppression. The in vitro tacrolimus response of peripheral blood mononuclear cells (PBMCs) before transplantation was compared to the clinical outcome up to 4 weeks after operation in 28 living-donor liver transplant recipients treated with tacrolimus. The tacrolimus IC 50 values against concanavalin A-induced PBMC blastogenesis in vitro were calculated. These recipients were classified into two groups with the mean tacrolimus IC 50 (0.18 ng/ml) as the cutoff point, after which the clinical outcome between the patient groups was compared. The allograft rejection incidence in the low-sensitivity group (IC 50 < 0.18 ng/ml; n = 16) was 6/12 (50.0%), which was significantly higher than the incidence of 2/16 (12.5%) in the high-sensitivity group (IC 50 > 0.18 ng/ml; n = 12) ( p = 0.0297). In contrast, the infection incidence in the high-sensitivity group was 6/16 (37.5%), which was significantly higher than that of the low-sensitivity group (1/12; 8.3%) ( p = 0.0401). These data suggest that patients exhibiting a low PBMC sensitivity to tacrolimus have a risk of rejection, whereas highly sensitive patients have a risk of infection in living-donor liver transplantations under tacrolimus therapy.https://doi.org/10.1177/096368970901805-622 |
| spellingShingle | Abuduxukuer Mijiti Naoto Matsuno Hironori Takeuchi Sakae Unezaki Takeshi Nagao Toshihiko Hirano Clinical Significance of the Cellular Pharmacodynamics of Tacrolimus in Living-Donor Liver Transplantation Cell Transplantation |
| title | Clinical Significance of the Cellular Pharmacodynamics of Tacrolimus in Living-Donor Liver Transplantation |
| title_full | Clinical Significance of the Cellular Pharmacodynamics of Tacrolimus in Living-Donor Liver Transplantation |
| title_fullStr | Clinical Significance of the Cellular Pharmacodynamics of Tacrolimus in Living-Donor Liver Transplantation |
| title_full_unstemmed | Clinical Significance of the Cellular Pharmacodynamics of Tacrolimus in Living-Donor Liver Transplantation |
| title_short | Clinical Significance of the Cellular Pharmacodynamics of Tacrolimus in Living-Donor Liver Transplantation |
| title_sort | clinical significance of the cellular pharmacodynamics of tacrolimus in living donor liver transplantation |
| url | https://doi.org/10.1177/096368970901805-622 |
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