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

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).

One-year monitoring of changes to kidney-pancreas waiting time criteria: An OPTN analysis

Purpose: In 2018, the OPTN board approved changes to kidney-pancreas (KP) waiting time criteria. KP candidates accrued waiting time if they were (1) on insulin and had a C-peptide <=2ng/mL or (2) on insulin and had a C-peptide >=2ng/ mL and had a BMI <=30kg/m∧2 which was the maximum allowable BMI. Since 7/11/2019 candidates must be on insulin, registered for a KP, and meeting kidney waiting time criteria. Methods: Registrations added to the waitlist and transplants between 7/11/2018- 7/10/2019 (pre-implementation) or 7/11/2019-7/10/2020 (post-implementation) were compared. Data originated from OPTN waitlist, Transplant Candidate Registration forms and Transplant Recipient Registration forms as of 10/16/2020. Results: 1,389 registrations were added to KP and 42,229 to kidney alone (KI) waitlists (pre-implementation);854 KP and 19,196 KI transplants performed. 1,401 registrations were added to KP and 19,493 KI waitlists (post-implementation);814 KP and 19,493 KI transplants performed. The proportion of type 2 diabetes (T2DM) KP candidates and recipients increased from 23.29% to 27.45% and 21.41% to 27%, respectively (Table 1). Candidate mean BMI increased from 25.7 to 26.3. KP recipients with T2DM and C-peptide >2ng/mL had higher median BMIs than those with lower C-peptide. KP post-transplant outcomes stratified by ethnicity, BMI, and diabetes status remained similar. The proportion of KI candidates and recipients remained roughly unchanged. Pediatric KI organ offers increased (527 to 592 offers per 100 active patient-years) but transplants remained unchanged. Conclusions: Changes in KP waiting time criteria did not adversely affect KI or pediatric KI candidates. Removing the BMI cutoff for obese patients with T2DM resulted in higher BMI KP transplants with equivalent post-transplant outcomes compared to lower BMI recipients. Although total KP transplants were slightly less in the post-implementation period, registrations were more and the transplant volumes were likely adversely affected by the COVID-19 pandemic.