TABLE 3.

RANDOMIZED TRIALS OF CALCINEURIN-INHIBITOR MINIMIZATION IN THE FIRST YEAR POST-LIVER TRANSPLANTATION

AUTHOR	N	STUDY DESIGN	MAJOR FINDINGS
Early (<1 month) CNI minimization studies
Yoshida (51)	148	Immediate post-LT: DAC + reduced TAC delayed 6 days vs. standard TAC	Improved GFR in reduced, delayed TAC No difference in AR rates
Neuberger (52)	525	Immediate post-LT: standard TAC vs. reduced-dose TAC+MMF vs. DAC + reduced TAC delayed 5 days + MMF	Significantly less drop in GFR in reduced, delayed TAC Less AR in reduced, delayed TAC
Calmus (53)	199	Immediate post-LT: DAC + standard TAC delayed 5 days vs. standard TAC	No difference in month 12 SCr > 1.43 mg/dL No difference in AR rates
Boudjema (54)	195	Immediate post-LT: reduced TAC + MMF vs. standard TAC	Significantly better GFR at month 12 in reduced TAC + MMF Significantly less AR in reduced TAC+MMF
Klintmalm (55)	250	Immediate post-LT: BAS + BELA MI + MMF vs. BELA MI + MMF vs. BELA LI + MMF vs. TAC + MMF vs. TAC	Significantly better month 12 GFR in all BELA groups Significantly higher AR rates in all BELA groups Significantly diminished month 12 survival in BELA LI + MMF
Asrani (56)	222	Immediate post-LT: standard TAC vs. reduced TAC + SRL	No difference in GFR Graft loss, death, vascular thrombosis and sepsis higher in reduced TAC + SRL
Delayed (1–12 month) CNI minimization studies
Teperman (57)	293	Week 4–12 post-LT: CNI + MMF vs. CNI to SRL+ MMF	Significant month 12 eGFR increase in SRL + MMF High side effects and discontinuation in SRL + MMF Higher rejection rate in SRL + MMF
De Simone (58) Saliba (59) Fischer (60)	719	Week 4 post-LT: TAC elimination plus EVR vs. reduced TAC + EVR vs. standard TAC	Month 12/24/36 eGFR superior for reduced TAC + EVR Reduced incidence and severity of AR in reduced TAC + EVR TAC elimination arm stopped due to high AR rates
Fischer (61)	203	Week 4 post-LT: BAS induction for all; CNI to EVR vs. CNI continuation	Significant improvement in GFR with EVR conversion No difference in AR rates
Abdelmalek (71)	607	Month 6–144: CNI to SRL vs. CNI continuation	No improvement in GFR with SRL conversion Higher AR rates with SRL conversion

AR: Acute Rejection; BAS: Basiliximab; BELA: Belatacept; CNI, calcineurin inhibitor; DAC: Daclizumab; DSA: Donor Specific Antibody; eGFR: Estimated Glomerular Filtration Rate; ESRD: End Stage Renal Disease; EVR: Everolimus; eGFR: Glomerular Filtration Rate; MMF: Mycophenolate Mofetil; mTOR-I: Molecular Target of Rapamycin Inhibitor; NAC: N-Acetylcysteine; SRL: Sirolimus; TAC: Tacrolimus.