Sirolimus Long-Term Tolerability and Impact on Kidney Function in Lung Transplantation: A Single-Center Experience

Transplant Proc. 2023 Dec;55(10):2470-2477. doi: 10.1016/j.transproceed.2023.09.027. Epub 2023 Oct 25.

Abstract

Background: After lung transplant, 2 common complications are calcineurin inhibitor (CNI) induced nephrotoxicity and bronchiolitis obliterans syndrome. The objective of this study was to investigate the long-term effects of sirolimus conversion after lung transplantation.

Methods: This was a retrospective cohort study of patients who had undergone lung transplantation at a single center from June 2003 to December 2016. We compared patients converted to a sirolimus-based regimen to those maintained on our standard tacrolimus-based regimen. Kidney function, pulmonary function, and immunosuppression concentrations were compared between the groups. Additionally, indications, toxicity monitoring parameters, and discontinuation rates for sirolimus were collected.

Results: During the study period, 176 of the 205 patients who underwent lung transplants were converted to a sirolimus-containing regimen (86%). The most common reason for sirolimus initiation was impairment of kidney function or CNI-associated neurotoxicity. Sirolimus was initiated at a median of 150 days post-transplantation and continued for a medium time of 5.02 (2.27-7.85) years. Of those patients converted to sirolimus, 39 (22%) had sirolimus subsequently discontinued secondary to an adverse event. No difference in pulmonary function was found between the groups at 1- and 3-years post-transplantation. In the sirolimus group, the median estimated glomerular filtration rate improved by 8.6 mL/min/1.73 m2 at 3 months post-conversion (P < .001), which was maintained at both 1 and 3 years (P = .014 and .025, respectively).

Conclusion: Sirolimus is a viable immunosuppressant option after lung transplant, which successfully allows for the reduction or withdrawal of the CNI, resulting in sustained improvement in kidney function.

MeSH terms

  • Calcineurin Inhibitors / adverse effects
  • Glomerular Filtration Rate
  • Graft Rejection
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Kidney
  • Lung Transplantation* / adverse effects
  • Retrospective Studies
  • Sirolimus* / adverse effects

Substances

  • Sirolimus
  • Immunosuppressive Agents
  • Calcineurin Inhibitors