Elsevier

Transplantation Proceedings

Volume 42, Issue 8, October 2010, Pages 3053-3054
Transplantation Proceedings

Immunosuppression
Pneumonitis Associated With Mammalian Target of Rapamycin Inhibitors in Renal Transplant Recipients: A Single-Center Experience

https://doi.org/10.1016/j.transproceed.2010.07.066Get rights and content

Abstract

Background

The mammalian target of rapamycin inhibitors (mTORi) sirolimus (Si) and everolimus (Ev) induce pneumonitis, an unusual but potentially fatal adverse effect. We report 8 cases of suspected mTORi-induced pneumonitis over a 9-years experience from 2000 to 2009.

Methods

The switch from a calcineurin inhibitor (CNi) was made due to chronic transplant nephropathy, tumors, nephrotoxicity, or for rejection prophylaxis.

Results

One hundred six patients were switched from CNi to Si (n = 29) or Ev (n = 134). Twenty-five additional patients were treated de novo with mTORi. The 8 patients (3 Si, 5 Ev) who developed pneumonitis included 5 females and 3 males of median age, 59.1 years (range, 40–68). The median time from switch to pneumonitis onset was 292 days (range, 60–982). The clinical presentation included fatigue (n = 6), fever (n = 7), dyspnea (n = 6), dry cough (n = 6), and weight loss (n = 5). In most cases, imaging tests (chest radiograph, computerized tomography) revealed bilateral lower lobe involvement. Bronchoalveolar lavage showed a lymphocytic alveolitis in 5 subjects with negative cultures. All patients recovered after mTORi withdrawal. All patients were treated with antibiotics and five with steroids.

Conclusion

mTORi associated pneumonitis is not a rare disease. It is equally induced by Si or Ev. Pneumonitis was not apparently dependent on the drug dose or the blood levels. Discontinuation of mTORi seems to be the safest treatment option to avoid pulmonary fibrosis or a fatal outcome.

Section snippets

Patients and Methods

We reviewed the medical records at a single renal transplantation center of 186 patients receiving (Si); n = 40; (11 de novo and 29 after conversion) (Ev); n = 146; (14 de novo and 132 after conversion). The de novo cases included patients in the Spanish trials in 2000 (Si) and 2005 (Ev). The patients were switched to mTORi owing to chronic transplant nephropathy renal CNi toxicity, cancer, or prophylaxis. Seven patients underwent baseline treatment with cyclosporine, 5 with azathioprine 2 with

Results

Among 186 patients receiving mTORi, 8 (4.3%) were identified with interstitial pneumonitis, 3 with Si 5 with Ev. The patient characteristics are summarized in Table 1. Only 1 patient with de novo use of mTORi (Si) developed pneumonitis (4%) and 7/161 (4.34%) after late conversion. The 7 patients who underwent late conversion, at 7–13 years after transplantation due to renal dysfunction (n = 4), prophylaxis of CNi toxicity or tumor (n = 3) skin plus parotid cancer (n = 1). The clinical

Discussion

The frequency of interstitial pneumonitis is increased in renal transplant recipients treated with mTORi. Our study revealed 8/186 cases (4.3%) with pneumonitis, consistant with the estimated frequencies of 4%–11%.1, 2, 3 Weiner et al1 presented 11 cases summarizing the literature on pneumonitis associated with Si among > 60 cases between 2004 and 2007. Most cases have been related to Si, although more recently similar data have been published with Ev.2, 3 All of our patients underwent late

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