Induction immunosuppression efficacy in pancreas and kidney transplantation in the SARS-CoV-2 era

ABSTRACT

Purpose: Lymphocyte depleting induction is associated with increased risk of infection. Our institution adopted a stratified induction protocol with the intent to decrease risk for recipients exposed to SARS-CoV-2. Baseline protocol was 6-7.5 mg/ kg thymoglobulin with a 3 dose steroid taper. This was modified to a protocol based on immunologic risk. Low risk group included KTA (PRA <20%) was basiliximab 40 mg and 4 week steroid taper;intermediate group was KTA (PRA 20-80%) or SPK (PRA <80%) and consisted of thymo 2 mg/kg and basiliximab 40 mg with 4 week steroid taper;high risk group included any recipient with PRA >80%, PTA, positive DSA and induction was unchanged from the pre-SARS-CoV-2 protocol. All recipients received tacrolimus/MMF maintenance. The primary objective was to evaluate the effect of adjusting induction immunosuppression on acute cellular rejection (AR) and infection rates. Methods: Outcomes of all adult transplants performed between March 24-October 18, 2020 were reviewed. Time to first infection and AR was analyzed using Kaplan- Meier curves. Patients were censored at the earliest of death, graft failure or 10/22/20. Results: 81 patients were assessed 61 KTA, 2 PTA, 18 SPK. Demographics 69.1% Caucasian, 59.3% male, 84.0% primary transplant and 76.5% deceased donor. 2 grafts were lost one due to thrombosis on POD 0 and the other due to primary non function. There were 2 deaths one due to CVA/MDR TB and another due to NSTEMI. Populations of the 3 risk groups low (16), intermediate (33) and high (32). In the low risk group there were 2 (12.5%) AR within 6 weeks of transplant. One of these patients developed AMR, BK and CMV. The intermediate group included 6 (18.2%) recipients who developed AR. 2 of these recipients developed 2 AR episodes, the first episodes were within 4 weeks of transplant. The first had Banff 1A in addition to AMR followed by borderline AR a month after initial biopsy. The second had 2 episodes of borderline AR and that graft ultimately failed due to primary non function. Of note the pathology of the other 4 recipients was consistent with borderline AR. There were 2 (6.3%) AR in the high risk group. The first was 1A within 6 weeks of transplant, this patient also developed EBV and CMV. The second was IIA within 3 weeks of transplant. There was no significant difference in AR rates among these groups (log rank p-value 0.396). No significant difference in overall infection rate (p-value 0.482), bacterial (p-value 0.906), fungal (p-value 0.553) or viral (p-value 0.494). An asymptomatic recipient tested positive for SARS-CoV-2 in the high risk group 2 months following KTA. Conclusions: Optimal induction regimens for pancreas and kidney transplant in the SARS-CoV-2 era remain unclear. Although rejection rates in the abbreviated induction groups were slightly higher, most were borderline. Short-term infection rate did not seem to be impacted. Tailored induction regimens stratified by risk may be safe and effective during this pandemic era and beyond. (Table Presented).