Interstitial pneumonitis caused by everolimus: a case-cohort study in renal transplant recipients

The use of inhibitors of the mammalian target of rapamycin (mTORi) in renal transplantation is associated with many side effects, the potentially most severe being interstitial pneumonitis. Several papers have reported on sirolimus-induced pneumonitis, but less is published on everolimus-induced pneumonitis (EIP). Data on risk factors for contracting EIP are even more scarce. In the present case-cohort study in renal transplant recipients (RTR), we aimed to assess the incidence and risk factors of EIP after renal transplantation. This study is a retrospective substudy of a multicenter randomized controlled trial. All patients included in the original trial and treated with prednisolone/everolimus were included in this substudy. RTR who developed EIP were identified as cases. RTR without pulmonary symptoms served as controls. Thirteen of 102 patients (12.7%) developed EIP. We did not find any predisposing factors, especially no correlation with everolimus concentration. On pulmonary CT scan, EIP presented with an organizing pneumonia-like pattern, a nonspecific interstitial pneumonitis-like pattern, or both. Median time (range) to the development of EIP after start of everolimus was 162 (38-407) days. In conclusion, EIP is common in RTR, presenting with an organizing pneumonia, a nonspecific interstitial pneumonitis-like pattern, or both. No predisposing factors could be identified (Trial registration number: NTR567 (www.trialregister.nl), ISRCTN69188731).