Background: Interindividual variability in dosage requirements of the calcineurin inhibitor immunosuppressive agents cyclosporine and tacrolimus after liver transplantation may result from differences in the CYP3A activity of the liver graft. Early postoperative erythromycin breath test (ERMBT) is an in vivo measure of graft CYP3A activity. This study evaluates the usefulness of an early postoperative ERMBT in predicting early morbidity in liver transplant recipients.
Methods: In 26 liver transplant recipients, ERMBT was performed within 2 hr after transplantation. Main end points were the occurrence of cyclosporine and tacrolimus nephrotoxicity, episodes of early graft rejection, early graft function, and graft survival.
Results: Cyclosporine and tacrolimus nephrotoxicity were associated with low postoperative ERMBT values (mean 0.63%+/-0.25% 14C/hr vs. 1.35%+/-0.84% 14C/hr, P=0.02). No significant association between early graft rejection and ERMBT values was demonstrated. There was a significant inverse correlation between postoperative ERMBT values and the time to normalization of international normalized ratio as a measure of early graft function (r=-0.78, P<0.001). Graft loss was associated with low postoperative ERMBT values (0.21%+/-0.15% 14C/hr vs. 1.09%+/-0.72% 14C/hr, P=0.002).
Conclusion: An early postoperative ERMBT may be useful in predicting the development of cyclosporine and tacrolimus nephrotoxicity, severe graft dysfunction, or even graft loss in liver transplant recipients when calcineurin inhibitors are administered according to protocols. Whether ERMBT results may be used to individualize dosage of calcineurin inhibitors needs to be explored.