Relationship between postoperative erythromycin breath test and early morbidity in liver transplant recipients.
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).


CONCLUSIONS
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.
Schmidt
Lars E
LE
Department of Hepatology, Rigshospitalet, Copenhagen, Denmark. lars.schmidt@dadlnet.dk.
Rasmussen
Allan
A
Kirkegaard
Preben
P
Dalhoff
Kim
K
D000328:Adult; D000900:Anti-Bacterial Agents; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001944:Breath Tests; D016572:Cyclosporine / Q000009:adverse effects*; D051544:Cytochrome P-450 CYP3A; D004917:Erythromycin; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000401:mortality; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000401:mortality; D008099:Liver / Q000201:enzymology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011183:Postoperative Complications / Q000139:chemically induced / Q000175:diagnosis / Q000401:mortality; D011237:Predictive Value of Tests; D016559:Tacrolimus / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D004917:Erythromycin; D016572:Cyclosporine; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D016559:Tacrolimus