Renal Function and Pharmacogenetics in Renal Transplant Recipients Converted From Tac BID to Tac OD

Overview

In Kidney transplant recipients Once daily Tacrolimus has the poteb\]ntial advantage of better adnerence, and perhpas improvement in reanl function compred with the twice daily tacrolimus formulation. Our center has the largest experience in North America with once-daily tacrolimus ( advagraf) in Renal transplant recipients. Recently we converted \~500 stable patients from the twice daily to once-daily tacrolimus. We are interested in: 1. change in renal function 2. dose changes based on ethnic diveristy 3. dose changes based on pharmacogenetics This will helpnus understand better ways to utilize this anti-rejection medication

The Renal transplant program at St. Michael's is one of the largest in Canada. The CNI of choice since 2000 has been tacrolimus based therapy. In 2009 our program decided to switch from bid prograf to once daily advagraf for all de-novo renal transplant recipients (RTR). Our Advagraf experience is currently the largest in North America. Because of concerns regarding generic prograf, we began a conversion of \> 600 prevalent transplant patients on bid prograf to OD advagraf in January 2012. At present this is nearly completed. It has been recognized that dosing of tacrolimus is highly dependent on pharmacogenentic differences related to the CYP3A5 genotype. CYP3A%\*3 (nonexpressors) require significantly higher doses of tacrolimus than CYP3A5\*1 (expressers) with heterozygotes being somewhere in the middle. Our study will examine the demographics, renal function and tacrolimus dosing and Co levels, both pre and post conversion from tac BID, to tac OD in our cohort of converted patients. Of More scientific interest, will be to retrospectively determine the CYP3A5 genotypes in recipients who required significant dose adjustments in the tac OD following conversion and compare to a matched cohort of recipients in whom no dose adjustment was needed. The hypothesis is that recipients who require dose increase when converted from the BID to the OD formulation, will have a different CYP3A5 genotype and will tend towards CYP3A5\*3. This will be the largest cohort to look at this question. Specifically this may lead to better dosing of tac OD, if pre-emptive genotyping prior to transplantation were to be employed.