Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological risk
Abstract High intra-patient variability (IPV) of tacrolimus trough concentrations is increasingly recognized as a predictor of poor long-term outcomes in kidney transplant. However, there is a lack of information regarding the association between tacrolimus IPV and graft outcomes according to immuno...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-06-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-91630-4 |
| _version_ | 1818735664936517632 |
|---|---|
| author | Eun Jin Kim Soo Jin Kim Kyu Ha Huh Beom Seok Kim Myoung Soo Kim Soon Il Kim Yu Seun Kim Juhan Lee |
| author_facet | Eun Jin Kim Soo Jin Kim Kyu Ha Huh Beom Seok Kim Myoung Soo Kim Soon Il Kim Yu Seun Kim Juhan Lee |
| author_sort | Eun Jin Kim |
| collection | DOAJ |
| description | Abstract High intra-patient variability (IPV) of tacrolimus trough concentrations is increasingly recognized as a predictor of poor long-term outcomes in kidney transplant. However, there is a lack of information regarding the association between tacrolimus IPV and graft outcomes according to immunological risk. We analyzed tacrolimus IPV using the coefficient of variability from months 6–12 after transplantation in 1080 kidney transplant recipients. Patients were divided into two immunological risk groups based on pre-transplant panel reactive antibodies and donor-specific antibodies. High immunological risk was defined as panel reactive antibodies ≥ 20% or the presence of donor-specific antibodies. The effects of tacrolimus IPV on graft outcomes were significantly different between low and high immunological risk patients. A multivariable Cox regression model confirmed that high tacrolimus IPV was an independent risk factor for graft failure in the high risk group (HR, 2.90; 95% CI, 1.42–5.95, P = 0.004). In the high risk group, high tacrolimus IPV was also significantly associated with increased risk of antibody-mediated rejection (P = 0.006). In contrast, death-censored graft survival and antibody-mediated rejection in the low immunological risk group was not significantly different by tacrolimus IPV. High tacrolimus IPV significantly increases the risk of graft failure and antibody-mediated rejection in patients with high immunological risk. |
| first_indexed | 2024-12-18T00:24:51Z |
| format | Article |
| id | doaj.art-aa56608f5d0e4aaa9bab94b3baf9ec36 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T00:24:51Z |
| publishDate | 2021-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-aa56608f5d0e4aaa9bab94b3baf9ec362022-12-21T21:27:16ZengNature PortfolioScientific Reports2045-23222021-06-011111910.1038/s41598-021-91630-4Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological riskEun Jin Kim0Soo Jin Kim1Kyu Ha Huh2Beom Seok Kim3Myoung Soo Kim4Soon Il Kim5Yu Seun Kim6Juhan Lee7Department of Surgery, Yonsei University College of MedicineDepartment of Surgery, Yonsei University College of MedicineDepartment of Surgery, Yonsei University College of MedicineDepartment of Internal Medicine, Yonsei University College of MedicineDepartment of Surgery, Yonsei University College of MedicineDepartment of Surgery, Yonsei University College of MedicineDepartment of Surgery, Yonsei University College of MedicineDepartment of Surgery, Yonsei University College of MedicineAbstract High intra-patient variability (IPV) of tacrolimus trough concentrations is increasingly recognized as a predictor of poor long-term outcomes in kidney transplant. However, there is a lack of information regarding the association between tacrolimus IPV and graft outcomes according to immunological risk. We analyzed tacrolimus IPV using the coefficient of variability from months 6–12 after transplantation in 1080 kidney transplant recipients. Patients were divided into two immunological risk groups based on pre-transplant panel reactive antibodies and donor-specific antibodies. High immunological risk was defined as panel reactive antibodies ≥ 20% or the presence of donor-specific antibodies. The effects of tacrolimus IPV on graft outcomes were significantly different between low and high immunological risk patients. A multivariable Cox regression model confirmed that high tacrolimus IPV was an independent risk factor for graft failure in the high risk group (HR, 2.90; 95% CI, 1.42–5.95, P = 0.004). In the high risk group, high tacrolimus IPV was also significantly associated with increased risk of antibody-mediated rejection (P = 0.006). In contrast, death-censored graft survival and antibody-mediated rejection in the low immunological risk group was not significantly different by tacrolimus IPV. High tacrolimus IPV significantly increases the risk of graft failure and antibody-mediated rejection in patients with high immunological risk.https://doi.org/10.1038/s41598-021-91630-4 |
| spellingShingle | Eun Jin Kim Soo Jin Kim Kyu Ha Huh Beom Seok Kim Myoung Soo Kim Soon Il Kim Yu Seun Kim Juhan Lee Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological risk Scientific Reports |
| title | Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological risk |
| title_full | Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological risk |
| title_fullStr | Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological risk |
| title_full_unstemmed | Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological risk |
| title_short | Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological risk |
| title_sort | clinical significance of tacrolimus intra patient variability on kidney transplant outcomes according to pre transplant immunological risk |
| url | https://doi.org/10.1038/s41598-021-91630-4 |
| work_keys_str_mv | AT eunjinkim clinicalsignificanceoftacrolimusintrapatientvariabilityonkidneytransplantoutcomesaccordingtopretransplantimmunologicalrisk AT soojinkim clinicalsignificanceoftacrolimusintrapatientvariabilityonkidneytransplantoutcomesaccordingtopretransplantimmunologicalrisk AT kyuhahuh clinicalsignificanceoftacrolimusintrapatientvariabilityonkidneytransplantoutcomesaccordingtopretransplantimmunologicalrisk AT beomseokkim clinicalsignificanceoftacrolimusintrapatientvariabilityonkidneytransplantoutcomesaccordingtopretransplantimmunologicalrisk AT myoungsookim clinicalsignificanceoftacrolimusintrapatientvariabilityonkidneytransplantoutcomesaccordingtopretransplantimmunologicalrisk AT soonilkim clinicalsignificanceoftacrolimusintrapatientvariabilityonkidneytransplantoutcomesaccordingtopretransplantimmunologicalrisk AT yuseunkim clinicalsignificanceoftacrolimusintrapatientvariabilityonkidneytransplantoutcomesaccordingtopretransplantimmunologicalrisk AT juhanlee clinicalsignificanceoftacrolimusintrapatientvariabilityonkidneytransplantoutcomesaccordingtopretransplantimmunologicalrisk |