Scott, J.P.

Abstract Introduction: Calcineurin inhibitor (CNI) nephrotoxicity is a common complication following lung transplant. This is usually treated with dose reduction of CNI, addition of mammalian target of rapamycin inhibitor (mTORi), or rarely, CNI withdrawal which poses the risk of acute and chronic lung allograft rejection. Complete CNI withdrawal and transition to a mTORi based regimen for renal protection is scarcely described in literature with mixed results. Methods: We performed a single center, retrospective chart review of adult lung transplant recipients from January 2010-December 2022 to identify those who underwent complete CNI withdrawal and transition to a mTORi based immunosuppression regimen. Dual organ transplants and external transplant surgeries were excluded. Demographics, and clinical information on immunosuppressive regimens, renal function, rejection episodes, and outcomes were collected. This study was approved by the Mayo Clinic Institutional Review Board. Descriptive statistics were employed. Data is presented as N (%) or median (IQR). Results: A total of 52 patients who underwent CNI withdrawal were identified, and 38 patients (73.1%) were transitioned to a mTORi based regimen for renal failure. The median age at transplant was 59.1 years (IQR 54.2-63.3) and 57.9% were male. The most common transplant indication was pulmonary fibrosis (N = 21, 55.3%). No patients had pre-transplant chronic kidney disease stage 3 or higher. The median length of time from transplant to CNI withdrawal was 13.0 months (IQR 10.0-28.6). Most patients (N = 35 out of 38, 92%) discontinued mTORi and returned to a CNI based regimen after a median duration of use of 4.5 months (IQR 2.4-12.0) for an upcoming procedure/facilitate wound healing (N = 7, 20%), hypervolemia (N =7, 20%), death (N = 6, 17%), lung toxicity (N = 5, 14%), or worsening allograft function (N=5, 14%). Five patients (13.2%) developed ≥ A2 acute cellular rejection. Ten patients (26.3%) developed chronic lung allograft dysfunction. There was no change in creatinine at baseline (just prior to CNI withdrawal) compared to 12 (+/- 3) months after mTORi initiation (p = 0.36). Thirteen patients required dialysis (34.2%), four patients received renal transplants (10.5%), and 1 patient died on the renal transplant waitlist. Conclusions: Our case series demonstrates complete CNI withdrawal and transition to mTORi regimen is associated with short duration of therapy for most patients due to side effects and no change in creatinine one year after transition.