P1666ASSOCIATION OF TACROLIMUS TROUGH LEVEL AND DAILY DOSE RATIO WITH OUTCOMES IN A PROSPECTIVE PREVALENT COHORT OF KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Tacrolimus is an integral part of the immunosuppressive regimen after solid organ transplantation. Due to its narrow therapeutic window, it requires frequent serum trough level (C0) monitoring and dose adjustment. Both over-and under treatment may have harmful effects regarding overall mortality and graft survival due to increased risk of cardiovascular diseases, malignancies, new onset diabetes and rejection. C0 and total daily dose ratio (CD) has recently been suggested as a potential predictor of worse graft outcome in the early period after transplantation, however, long term prospective studies are lacking. We hypothesized the association between lower CD ratio and increased risk of death with functioning graft (DWFG), graft loss (GL) and overall death (D) in our prospective cohort study. Method Our study included 386 prevalent kidney transplant recipients (205(53%) males, median and IQR age of 47.5 (13.2) years, eGFR 53.5 (22.5) ml/min/1.73m2, time since last transplant 51 (26-79) months) out of a total of 993 enrolled between 2006-2007. Sociodemographic, past medical history, clinical and laboratory data were collected and CD was recorded at baseline and 1 year after the enrollment. The associations between CD and CD2 ratios and above mentioned outcomes were examined using survival models.. Results The median and IQR of CD was 2.1(1.4-3.2) at baseline and 2.0 (1.3-3.0) 1 year later (CD2). There was 46 (11.9%) DWFG, 79 (20.5%) GL and 68 (17.6%) D, respectively. After adjustment for important confounders (age, gender, eGFR, Charlson score, dialysis duration, donor age, rejection), neither CD (DWGL: HR 0.56(0.30-1.03) p=0.06; GL: HR 0.82(0.50-1.36) p=0.46; D: HR 0.79(0.48-1.32) p=0.38) nor CD2 (DWGL: HR 1.12(0.54-2.31) p=0.74; GL: HR 0.76(0.61-1.97) p=0.78; D: HR 1.19(0.64-2.20) p=0.59) found to be predictors of the outcomes. Conclusion CD ratio was not associated with increased risk of death with functioning graft, graft loss or overall death in our prevalent kidney transplant recipients.