title: Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome--a single-centre experience and review of the literature.
abstract: 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 mug/l (range: 6.2-38.7 mug/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 mug/l may increase the risk, but pneumonitis may also occur at blood trough levels as low as 6 mug/l. Since pneumonitis may recur during low-dose sirolimus treatment, discontinuation of sirolimus appears to be the safest treatment option.
authors.affiliation: Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Germany. stefan.weiner@ruhr-uni-bochum.de
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Weiner
authors.forename: Lorenz
authors.initials: L
authors.lastname: Sellin
authors.forename: Oliver
authors.initials: O
authors.lastname: Vonend
authors.forename: Peter
authors.initials: P
authors.lastname: Schenker
authors.forename: Nikolaus J
authors.initials: NJ
authors.lastname: Buchner
authors.forename: Markus
authors.initials: M
authors.lastname: Flecken
authors.forename: Richard
authors.initials: R
authors.lastname: Viebahn
authors.forename: Lars C
authors.initials: LC
authors.lastname: Rump
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000139:chemically induced* / Q000175:diagnosis; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus