Ruth Rahamimov1,2,3, Hagit Tifti-Orbach4, Boris Zingerman4,5, Hefziba Green6,4, Shira Schneider6, Avry Chagnac6,4,5, Eytan Mor7,4, Benjamin D Fox4,8, Benaya Rozen-Zvi6,4. 1. Department of Nephrology and Hypertension, Rabin Medical Center, Beilinson campus, 39, Jabutinsky st., Petah Tikva, Israel. rutir@clalit.org.il. 2. Department of Transplantation, Rabin Medical Center, Beilinson campus, Petah Tikva, Israel. rutir@clalit.org.il. 3. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. rutir@clalit.org.il. 4. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 5. Department of Nephrology and Hypertension, Rabin Medical Center, HaSharon campus, Petah Tikva, Israel. 6. Department of Nephrology and Hypertension, Rabin Medical Center, Beilinson campus, 39, Jabutinsky st., Petah Tikva, Israel. 7. Department of Transplantation, Rabin Medical Center, Beilinson campus, Petah Tikva, Israel. 8. Department of Pulmonology, Assaf Harofeh (Yitzhak Shamir) Medical Center, Zrifin, Israel.
Abstract
PURPOSE: High tacrolimus trough drug level variability was found to be associated with reduced graft survival. The primary goal of this study was to find whether reduction of exposure to high tacrolimus trough level variability in patients in which previously had high variability was associated with better graft survival. METHODS: All tacrolimus drug level values in patients that underwent kidney transplantation at our center between 2006 and 2015 were collected. Exposure to variability was calculated using a time-weighted coefficient of variability (TWCV). Time-dependent univariate and multivariate Cox proportional hazard models were used to analyze the primary outcome of graft survival and to determine a cutoff value for TWCV as a predictor of this outcome. RESULTS: A total of 878 patients were included in the study with a median follow-up of 1263 days. TWCV above 25% was significantly associated with reduced graft survival (HR3.66, 95% CI 2.3-5.8, p < 0.001). Of the 480 patients (54.7%) who had a cumulative TWCV of > 25% at a certain time during the follow-up, 110 (22.9%) later returned to a cumulative TWCV of less than 25%. Reduction of TWCV to values below 25% was associated with a hazard of graft loss that was not different from patients who had cumulative TWCV of less than 25% during the entire follow-up period (HR 1.81, 95% CI 0.71-4.62, p = 0.218 and HR 1.08, 95% CI 0.39-2.99, p = 0.780) in univariate and multivariate analyses, respectively. CONCLUSIONS: Monitoring TWCV can help detect the high-risk patients. Interventions intended to reduce variability on long-term graft survival may have a positive effect on graft survival.
PURPOSE: High tacrolimus trough drug level variability was found to be associated with reduced graft survival. The primary goal of this study was to find whether reduction of exposure to high tacrolimus trough level variability in patients in which previously had high variability was associated with better graft survival. METHODS: All tacrolimus drug level values in patients that underwent kidney transplantation at our center between 2006 and 2015 were collected. Exposure to variability was calculated using a time-weighted coefficient of variability (TWCV). Time-dependent univariate and multivariate Cox proportional hazard models were used to analyze the primary outcome of graft survival and to determine a cutoff value for TWCV as a predictor of this outcome. RESULTS: A total of 878 patients were included in the study with a median follow-up of 1263 days. TWCV above 25% was significantly associated with reduced graft survival (HR3.66, 95% CI 2.3-5.8, p < 0.001). Of the 480 patients (54.7%) who had a cumulative TWCV of > 25% at a certain time during the follow-up, 110 (22.9%) later returned to a cumulative TWCV of less than 25%. Reduction of TWCV to values below 25% was associated with a hazard of graft loss that was not different from patients who had cumulative TWCV of less than 25% during the entire follow-up period (HR 1.81, 95% CI 0.71-4.62, p = 0.218 and HR 1.08, 95% CI 0.39-2.99, p = 0.780) in univariate and multivariate analyses, respectively. CONCLUSIONS: Monitoring TWCV can help detect the high-risk patients. Interventions intended to reduce variability on long-term graft survival may have a positive effect on graft survival.
Authors: Kim H Piburn; Vaka K Sigurjonsdottir; Olafur S Indridason; Lynn Maestretti; Mary Victoria Patton; Anne McGrath; Runolfur Palsson; Amy Gallo; Abanti Chaudhuri; Paul C Grimm Journal: Clin J Am Soc Nephrol Date: 2022-07-26 Impact factor: 10.614