Extended use of RATG or basiliximab allows delayed CNI initiation in patients with renal dysfunction after heart transplantation

Background: Calcineurin inhibitors (CNI) may delay recovery from acute kidney injury after heart transplantation (HT). Oliguria is common after initiation of CNI and an advantage of antibody induction is that CNI may be avoided until renal function has recovered. When renal recovery is delayed, repeated antibody doses may be used to delay CNI initiation and bridge patients to renal recovery. Aim: The aim was to evaluate renal function and the incidence of rejection, infection and PTLD in patients with delayed renal recovery after HT who receive extended antibody induction in order to delay CNI initiation. Methods. We included 66 consecutive patients who underwent HT between January 2013 and December 2014 at Papworth Hospital. Patients were grouped according to induction received: (A) Standard induction with 3 doses antibody and (B) Extended induction with more than 3 doses antibody due to prolonged renal dysfunction after HT. The primary endpoint was need for renal replacement therapy or estimated glomerular filtration rate (eGFR) of <30 ml/min/1.73 m2 at 1 year post HT. Secondary endpoints were survival at 1 year after HT and episodes of treated rejection (ISHLT grade 2R or above), episodes of infection and development of PTLD during year 1. Results: There were no differences in recipient baseline characteristics. Patients in group B had older donor age (P = 0.02), longer ischaemic time (P = 0.02) and were more likely to have required post-transplant MCS (P < 0.01) and CVVH (P < 0.01). The primary endpoint was reached in 4.8% of group A, but 35.7% of group B despite delayed CNI initiation (P < 0.01). The median serum Creatinine at 1 year was 111 μmol/l in group A and 129 μmol/l in group B (P = 0.06). There was no difference in freedom from rejection at 1 month, 6 months and 1 year after HT (P = 0.32) and incidence of infection between groups (P = 0.62). No patients developed PTLD. Survival at 1 year was 93% in group A and 73% in group B (P = 0.03). All deaths were due to primary graft dysfunction and none due to acute rejection. Conclusion: Although we observed significant renal dysfunction at 1 year in patients with prolonged post-operative acute kidney injury, there was no increase in the incidence of rejection, infection or PTLD with use of extended antibody induction. Survival was lower in these patients, probably due to confounding by baseline characteristics and post-operative adverse events. Extended antibody induction may be a safe option in patients with postoperative renal dysfunction in whom delayed CNI initiation is desirable. (Table Presented).