CLINICAL IMMUNOSUPPRESSION - NEW AGENTS

C. Xiao¹, C. Wang², L. Liu³, Q. Fu^2
1Transplant Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou/CHINA, ²Department Of Organ Transplantation, First Affiliated Hospital, Sun Yat-sen University, Guangzhou/CHINA, ³Lab Of Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou/CHINA

Body: Introduction Transplant clinicians can control calcineurin inhibitors(CNI)concentration(Cmax,Cmin even AUC) by increase or decrease CNI dose but it is hard to contral CTCS. Stable state concentration curve shape of CNI correlated with higher acute rejection rate and drug toxicity in renal transplant.Because acute rejection is CNI dose-dependent,correlated with Cmax.CNI chronic renal toxicity is dose time-dependent,correlated with Cmin.This study used clearance rate constant(Kc) as an indicator to see if tacrolimus CTCS correlate with the kidney transplant clinical outcome. Methods We followed 43 early term (3~6month post renal transplant)renal allograft recipients for 1 year,who had been measured 10 time point tacrolimus concentration in 12 hours.AUC(0-12h),Cmax,Cmin,Cmax/Cmin,Kc,Ka,Cmax × Kc, Cmin / Kc,MDRD-eGFR were recorded or calculated at the same time.Acute rejection,infection,eGFR 1 year later,eGFR change rate were recorded.Recipient&rsquos Kc<0.15 as higher Kc group,n=18 Kc 0.15-0.3 as lower Kc group,n=25. Results Tacrolimus Kc was postive correlate with Cmax/Cmin,Cmax/AUC,absorption rate constant(Ka),and Cmax.Kc varied form 0.011 to 0.294.The higher Kc group had lower Acute rejection rate(0%vs.22.22%) ,lower infection rate(12%vs.22.22%) and lower Severe infection rate(4%vs.11.11%) and mortality(0%vs11.11 %)than lower Kc group.The higher Kc group also had higher 1 year later eGFR level (93.65±21.73vs. 86.10±32.17 ml/min/1.73m2)and eGFR change rate( 8.54%vs. 1.82 %) . ConclusionRenal allograft recipients with higher tacrolimus Kc will have a tall and narrow tacrolimus CTCS.Thoserecipients have a better kidney transplant clinical outcomes in acute rejection,infection,and prospective renal fuction.It may due to highertacrolimus peak concentration to suppress graft rejection and lower maintence concentration to decrease drug toxicity.We think that CTCS worthy of more research.

Disclosure: All authors have declared no conflicts of interest.