Modifying Tacrolimus-related Toxicity After Liver Transplantation Comparing Life Cycle Pharma Tacrolimus Versus Extended-released Tacrolimus: A Multicenter, Randomized Controlled Trial.

Background: The aim of this open-label, multicenter, randomized controlled study was to investigate whether the life cycle pharma (LCP)-tacrolimus compared with the extended-release (ER)-tacrolimus formulation results in a difference in the prevalence of posttransplant diabetes, hypertension and chronic kidney disease (CKD) at 12 mo after liver transplantation. Methods: Patients were 1:1 randomized to either of the 2 tacrolimus formulations. The primary endpoint was defined as a composite endpoint of any of 3 events: sustained (>3 mo postrandomization) posttransplant diabetes, new-onset hypertension, and/or CKD, defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 for >3 m during the follow-up. Results: In total, 105 patients were included. In the intention-to-treat analysis, a statistically significant lower proportion of liver transplant recipients in the LCP-tacrolimus group reached the composite primary endpoint at 12 mo compared with the ER-tacrolimus group (50.9% [27/53], 95% confidence interval [CI], 37.9%-63.9% versus 71.2% [37/52], 95% CI, 57.7%-81.7%; risk difference: 0.202; 95% CI, 0.002-0.382; P = 0.046). No significant difference was found in the per protocol analysis. In the intention-to-treat and per protocol population, fewer liver transplant recipients in the LCP-tacrolimus group developed CKD and new-onset hypertension compared with the ER-tacrolimus group. No differences in rejection rate, graft and patient survival were found. Conclusions: A statistically significant and clinically relevant reduction in the prevalence of the composite primary endpoint was found in the LCP-tacrolimus group compared with the ER-tacrolimus group in the first year after liver transplantation with comparable efficacy.

Clinical outcome after cyclosporine dose reduction based on C2 levels in long-term liver transplant patients.

BACKGROUND: Recent studies suggest that cyclosporine dose adjustment based on C2 levels results in improvement of renal function. This study investigates the effect on renal function after dose reduction based on the C2 levels in long-term liver transplant patients. METHODS: In 60 patients (>1 yr after transplantation), C2 levels were assessed (target 600 ng/mL +/- 20%). Dose reduction was performed when C2 >720 ng/mL. Serum creatinine concentrations were measured and creatinine clearance was calculated. RESULTS: Twenty-three patients (38%) had C2 values >720 ng/mL. After dose reduction, mean cyclosporine dose decreased by 25% (p < 0.01). Mean C2 value decreased by 42% (p < 0.01). Serum creatinine concentrations remained stable. After dose reduction two patients experienced recurrence of PBC, in one patient AIH recurred and rejection was diagnosed in one patient. CONCLUSION: Cyclosporine C2 concentrations above 720 ng/mL are common in long-term liver transplant patients. Dose reduction of 25% did not improve kidney function and was accompanied by immune activation.