BACKGROUND: High intrapatient tacrolimus variability has been associated with worse clinical outcomes postrenal transplantation. Theoretically, tacrolimus levels consistently outside the target therapeutic window may result in allograft dysfunction as subtherapeutic tacrolimus levels predispose to episodes of acute rejection, whereas supratherapeutic levels may cause nephrotoxicity. METHODS: We investigated the effect of tacrolimus variability in a "Symphony" style low-dose tacrolimus based regime, by collecting data from 432 patients over a 4-year period.Three hundred seventy-six patients were included, with a mean follow-up of 1495 days. Tacrolimus variability 6 to 12 months after renal transplantation was calculated, and outcomes were compared in low (n = 186) and high variability (n = 190) groups. RESULTS: High variability patients were found to be at increased risk of rejection during the first posttransplant year (P = 0.0054) and to have reduced rejection-free survival (hazard ratio, 1.953; 95% confidence interval, 1.234-3.093; P = 0.0054). High variability patients had significantly worse (P < 0.0001) glomerular filtration rates at 1, 2, 3, and 4 years posttransplant. High variability patients were at increased risk of allograft loss (hazard ratio, 4.928; 95% confidence interval, 2.050-11.85; P = 0.0004). CONCLUSIONS: This suggests that highly variable tacrolimus levels predict worse outcomes postrenal transplantation, although the causal nature of this relationship remains unclear. High tacrolimus variability may identify a subset of patients who warrant increased surveillance and patient education regarding dietary and medication compliance.
BACKGROUND: High intrapatient tacrolimus variability has been associated with worse clinical outcomes postrenal transplantation. Theoretically, tacrolimus levels consistently outside the target therapeutic window may result in allograft dysfunction as subtherapeutic tacrolimus levels predispose to episodes of acute rejection, whereas supratherapeutic levels may cause nephrotoxicity. METHODS: We investigated the effect of tacrolimus variability in a "Symphony" style low-dose tacrolimus based regime, by collecting data from 432 patients over a 4-year period.Three hundred seventy-six patients were included, with a mean follow-up of 1495 days. Tacrolimus variability 6 to 12 months after renal transplantation was calculated, and outcomes were compared in low (n = 186) and high variability (n = 190) groups. RESULTS: High variability patients were found to be at increased risk of rejection during the first posttransplant year (P = 0.0054) and to have reduced rejection-free survival (hazard ratio, 1.953; 95% confidence interval, 1.234-3.093; P = 0.0054). High variability patients had significantly worse (P < 0.0001) glomerular filtration rates at 1, 2, 3, and 4 years posttransplant. High variability patients were at increased risk of allograft loss (hazard ratio, 4.928; 95% confidence interval, 2.050-11.85; P = 0.0004). CONCLUSIONS: This suggests that highly variable tacrolimus levels predict worse outcomes postrenal transplantation, although the causal nature of this relationship remains unclear. High tacrolimus variability may identify a subset of patients who warrant increased surveillance and patient education regarding dietary and medication compliance.
Authors: Stephan R Seibert; David P Schladt; Baolin Wu; Weihua Guan; Casey Dorr; Rory P Remmel; Arthur J Matas; Roslyn B Mannon; Ajay K Israni; William S Oetting; Pamala A Jacobson Journal: Clin Transplant Date: 2018-10-31 Impact factor: 2.863
Authors: David J Taber; Zemin Su; James N Fleming; John W McGillicuddy; Maria A Posadas-Salas; Frank A Treiber; Derek Dubay; Titte R Srinivas; Patrick D Mauldin; William P Moran; Prabhakar K Baliga Journal: Transplantation Date: 2017-12 Impact factor: 4.939
Authors: Franc Andreu; Helena Colom; Laure Elens; Teun van Gelder; Ronald H N van Schaik; Dennis A Hesselink; Oriol Bestard; Joan Torras; Josep M Cruzado; Josep M Grinyó; Nuria Lloberas Journal: Clin Pharmacokinet Date: 2017-08 Impact factor: 6.447
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