(1130) - Timing of Tacrolimus Initiation and Impact on Renal Injury in Pediatric Heart Transplant Patients

Abstract

Strategies to reduce Calcineurin Inhibitor (CNI) related renal injury in post-transplant patients have not well studied in pediatric patients. It is known that early increase in creatinine post-cardiac surgery in pediatric patients was associated with long term morbidity and mortality. The purpose of this study is to look at the impact of early versus late CNI tacrolimus) introduction on renal function in pediatric heart transplant (HT) patients. Retrospective review of two successive protocols. The protocol (P1) prior to 03/2013 involved starting tacrolimus preoperatively and continuing Q12 thereafter while protocol (P2) post 03/2013, involved tacrolimus introduction between 36-48 hours post-HT along with standard induction and immunotherapy. 42 pediatric patients were treated per P2 with 42 P1 nested controls. The demographics, diagnosis, wait time, listing status, donor age, race, operative parameters were all comparable between P1 and P2 (p>0.05). Tacrolimus was started preoperatively in all patients in P1 while 5/42, 31/42 and 42/42 patients in P2 received tacrolimus on post-operative days (POD) 1, 2 and 3 respectively. Average time to therapeutic level in P1 was 2.5 days and in P2 was 4.5 days. The postoperative support and course was similar in the two groups. Renal function: Urine output and eGFR in the early post-operative period were significantly higher in P2. The urine output was significantly higher on transplant day (2.07 ml/kg/hr vs 3.1 ml/kg/hr, p =0.003) and POD 1 in P2. eGFR was significantly higher on POD2 in P2 (80.3 vs 55.9, p=0.01). These differences were not sustained at 3 and 6 months post HT. Development of AKI (>50% increase in SCr over baseline) was similar (19/39 and 20/42 in P1 and P2, p>0.05) at POD2. Mean increase of SCr from baseline was 99.2% in P1 and 66.7% in P2. pRIFLE scores at day 2, 3 months and 6 months were similar in the two groups. Major outcomes such as significant rejection and death before 6 months, were similar in the two groups. The strategy of delayed introduction of CNI (tacrolimus) lead to statistically significant urine output as well as a higher eGFR early postoperatively. However, these effects were not sustained. Late introduction of CNI, therefore, may be an acceptable renoprotective strategy during the vulnerable post-operative period, without any notable detriments.