mTOR inhibitors after lung transplantation: a real-life experience

Background: The mammalian target of rapamycin (mTOR) inhibitors in combination with calcineurin inhibitors (CNIs), antimetabolites and corticosteroids for immunosuppression after lung transplantation (TPL) have gained importance in patients with chronic kidney disease (CKD). The goal of this study was to characterize lung transplant recipients (LTR) treated with mTOR inhibitors, with a special focus on kidney function.

Methods: LTR transplanted at the University Hospital Zurich between December 1992 and April 2022 were analyzed. Demographics, estimated glomerular filtration rate (eGFR) before and after mTOR initiation, TPL circumstances, immunosuppressive regimens, and allograft function were recorded. We used linear regression to calculate the Mitch curves and a linear mixed-effects model to compare the eGFR.

Results: Of all LTR, 70/593 (12%) received mTOR inhibitors. Intolerance or adverse events of antimetabolites were the most common indications for mTOR inhibitor introduction. Discontinuation in 34/70 (49%) was often related to planned or urgent surgery to prevent impaired wound healing. The majority of patients had a preserved baseline eGFR at mTOR inhibitor introduction with CKD Kidney Disease Improving Global Outcomes (KDIGO) stage G1 or 2. The mean annual eGFR decline changed significantly from -16.19 mL/min/1.73 m²/year [95% confidence interval (CI): -22.27 to -10.11] 12 months before to -6.16 mL/min/1.73 m²/year (95% CI: -13.37 to 1.05) 12 months after mTOR initiation (P=0.009) showing better outcomes with earlier mTOR inhibitor initiation after lung TPL.

Conclusions: This retrospective study suggests stabilization of kidney function after mTOR inhibitor initiation in LTR documented by a slower eGFR decline after mTOR inhibitor introduction with better outcomes early after lung TPL. Intolerance or adverse events of antimetabolites are important indications for the introduction of mTOR inhibitors. A relatively high discontinuation rate (49%) can be explained by planned discontinuation of mTOR inhibitors prior to surgery to avoid impaired wound healing.