Pharmacogenetic determinants of calcineurin inhibitor associated nephrotoxicity in liver transplant patients

Abstract

The use of calcineurin inhibitors (tacrolimus and cyclosporine) has become standard of care in post-transplant immunosuppression. While these medications have greatly reduced organ rejection, they can cause nephrotoxicity and renal failure in some patients. A possible risk factor for this toxicity may be pharmacogenetic variability in the enzymes involved in the clearance of the calcineurin inhibitors. We conducted a prospective study in liver transplant patients at the University of Washington to evaluate whether or not variation in the genes encoding CYP3A5 (*1 vs *3) and P-glycoprotein (MDR2677, MDR3435, or MDR1236) were associated with a decline in kidney function (assessed by the estimated glomerular filtration rate) in liver transplant patients using continuous calcineurin inhibitor therapy. This study did not find a significant association between the inheritance of the CYP3A5 *1 or *3 alleles, or MDR2677, MDR3435, or MDR1236 alleles and the rate of decline of estimated glomerular filtration rate in post-liver transplant patients.