BACKGROUND: Use of tacrolimus (TAC) is pivotal to renal transplant (RT) immunosuppressive maintenance regimens. The aim of this study was to evaluate the relationship between TAC trough levels and the development of acute rejection (AR). MATERIAL AND METHODS: This was a retrospective cohort study. We included recipients transplanted between 01/2008 and 05/2012. Regression analyses (Cox's proportional hazards model) and sub-analysis of AR and TAC levels over different time periods were performed. RESULTS: We included 198 patients with an average age of 32 years (±12.1) and predominantly male (54.5%). Mean follow-up was 2 years (min-max 15d - 5.2yrs). Sixty-two AR events were documented (BL: 31, Cellular AR: 19, Humoral AR: 12). We found that TAC levels (HR 0.76, 0.65-0.88, p<0.001), a high risk for CMV infection (D+/R-) (HR 2.92, 1.47-1.014, p=0.002), pre-transplant donor-specific HLA antibodies (DSA) (HR 3.04 1.29-7.16, p=0.011), and post-RT DSA (HR 2.4, 1.16-4.9, p=0.018) were significantly associated with AR. The relationship between TAC levels and rejection was independent of follow-up duration. CONCLUSIONS: In this analysis, TAC though levels were directly related to AR events; trough levels >8 ng/ml were the most effective in decreasing immunological adverse events. A decrease in TAC levels throughout the post-transplant follow-up period should be considered due to its possible association with AR events.
BACKGROUND: Use of tacrolimus (TAC) is pivotal to renal transplant (RT) immunosuppressive maintenance regimens. The aim of this study was to evaluate the relationship between TAC trough levels and the development of acute rejection (AR). MATERIAL AND METHODS: This was a retrospective cohort study. We included recipients transplanted between 01/2008 and 05/2012. Regression analyses (Cox's proportional hazards model) and sub-analysis of AR and TAC levels over different time periods were performed. RESULTS: We included 198 patients with an average age of 32 years (±12.1) and predominantly male (54.5%). Mean follow-up was 2 years (min-max 15d - 5.2yrs). Sixty-two AR events were documented (BL: 31, Cellular AR: 19, Humoral AR: 12). We found that TAC levels (HR 0.76, 0.65-0.88, p<0.001), a high risk for CMV infection (D+/R-) (HR 2.92, 1.47-1.014, p=0.002), pre-transplant donor-specific HLA antibodies (DSA) (HR 3.04 1.29-7.16, p=0.011), and post-RT DSA (HR 2.4, 1.16-4.9, p=0.018) were significantly associated with AR. The relationship between TAC levels and rejection was independent of follow-up duration. CONCLUSIONS: In this analysis, TAC though levels were directly related to AR events; trough levels >8 ng/ml were the most effective in decreasing immunological adverse events. A decrease in TAC levels throughout the post-transplant follow-up period should be considered due to its possible association with AR events.
Authors: W S Oetting; B Wu; D P Schladt; W Guan; R P Remmel; R B Mannon; A J Matas; A K Israni; P A Jacobson Journal: Pharmacogenomics J Date: 2017-11-21 Impact factor: 3.550
Authors: William S Oetting; Baolin Wu; David P Schladt; Weihua Guan; Rory P Remmel; Casey Dorr; Roslyn B Mannon; Arthur J Matas; Ajay K Israni; Pamala A Jacobson Journal: Pharmacogenomics Date: 2018-01-10 Impact factor: 2.533
Authors: Franny Jongbloed; Ron W F de Bruin; Harry Van Steeg; Piet Beekhof; Paul Wackers; Dennis A Hesselink; Jan H J Hoeijmakers; Martijn E T Dollé; Jan N M IJzermans Journal: Aging (Albany NY) Date: 2020-07-11 Impact factor: 5.682