Journal Article

Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature

Stefan M. Weiner, Lorenz Sellin, Oliver Vonend, Peter Schenker, Nikolaus J. Buchner, Markus Flecken, Richard Viebahn and Lars C. Rump

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 22, issue 12, pages 3631-3637
Published in print December 2007 | ISSN: 0931-0509
Published online July 2007 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfm420
Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature

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Background. The introduction of sirolimus as an immunosuppressive drug for renal transplantation has lead to an increase of unexplained interstitial pneumonitis.

Methods. Out of a cohort of 115 patients receiving sirolimus for prophylaxis of renal and/or pancreas transplant rejection, 11 patients with interstitial pneumonitis were identified. Medical records and published case series were reviewed to identify risk factors associated with the occurrence of pneumonitis.

Results. Eleven out of 80 patients (14%) with late switch to sirolimus developed pneumonitis, in contrast to none of the 35 patients with de novo use of sirolimus. The mean sirolimus trough level at presentation was 16.7 μg/l (range: 6.2–38.7 μg/l). Glomerular filtration rate (GFR) was significantly lower in patients with pneumonitis compared to controls (mean 21.3 ± 3.9 ml/min vs 38.65 ± 2.14 ml/min P = 0.002). Two patients needed haemodialysis shortly before pneumonitis was diagnosed. In a multivariate analysis only serum creatinine and GFR were independent predictors for pneumonitis.

Sirolimus was discontinuated in five patients and the dose reduced in the other patients. Pneumonitis resolved within 14–28 days in all patients. One patient who had continued low-dose sirolimus treatment relapsed after 5 months, the other five patients had no relapse over a period of 15–48 months.

Pooled analysis of our data and other published case series showed that the frequency of pneumonitis in patients with de novo use of sirolimus is significantly lower than in patients with late switch [5/133 (4%) vs 46/326 (14%) patients, P = 0.0024].

Conclusions. Late switch to sirolimus and impaired renal function are risk factors for pneumonitis. A sirolimus blood trough level above 12 μg/l may increase the risk, but pneumonitis may also occur at blood trough levels as low as 6 μg/l. Since pneumonitis may recur during low-dose sirolimus treatment, discontinuation of sirolimus appears to be the safest treatment option.

Keywords: pancreas transplantation; pneumonitis; rapamycin; renal transplantation; risk factor; sirolimus

Journal Article.  3377 words.  Illustrated.

Subjects: Nephrology

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