PMID- 19715862
OWN - NLM
STAT- MEDLINE
DCOM- 20100111
LR  - 20211203
IS  - 1873-2623 (Electronic)
IS  - 0041-1345 (Linking)
VI  - 41
IP  - 6
DP  - 2009 Jul-Aug
TI  - Sirolimus and everolimus induced pneumonitis in adult renal allograft recipients: 
      experience in a center.
PG  - 2163-5
LID - 10.1016/j.transproceed.2009.06.003 [doi]
AB  - Mammalian target of rapamycin (mTOR) inhibitors induce pneumonitis, an unusual 
      but potentially fatal side effect of this drug group. We retrospectively 
      collected the cases of pneumonitis induced by sirolimus or everolimus among 1471 
      adult cadaveric renal transplant recipients who were grafted at our institution 
      from 1980-2008. Due to chronic transplant dysfunction or tumor, 205 patients were 
      switched from calcineurin inhibitors to sirolimus (n = 88) or to everolimus (n = 
      117). Six patients (2.9%) developed pneumonitis: 1 was associated with sirolimus 
      and 5 with everolimus (5 males and 1 female; median age, 60 years [range, 47-73 
      years]). Median times from conversion to pneumonitis onset were 34 days in 4 
      patients (range, 24-46 days) and 491 days in 2 subjects (range, 454-528 days). 
      The mean drug trough level at presentation was 8.2 microg/L (range, 5.5-13.8 
      microg/L). The most common symptoms were dry cough (n = 6), fever (n = 5), and 
      dyspnea (n = 4). Imaging tests revealed lower lobe involvement in all patients. 
      Bronchoalveolar lavage performed in 4 patients showed lymphocytic alveolitis. All 
      patients completely recovered after drug withdrawal. Five patients received 
      steroids, 5 were switched to a calcineurin inhibitor, and 1 was switched to the 
      other mTOR inhibitor. In conclusion, mTOR inhibitor-associated pneumonitis is a 
      rare disease. Sirolimus did not cause more cases of pneumonitis than everolimus. 
      Pneumonitis development was not dependent upon the drug blood level. Lower lobe 
      involvement and lymphocytic alveolitis were usually present. Discontinuation of 
      the mTOR inhibitor with steroid prescription resulted in adequate outcomes. A 
      change to the other mTOR inhibitor should be contemplated if patient 
      circumstances require this type of immunosuppression.
FAU - Rodriguez-Moreno, A
AU  - Rodriguez-Moreno A
AD  - Department of Nephrology, Hospital Clinico San Carlos, Madrid, Spain. 
      arodriguezmo.hcsc@salud.madrid.org
FAU - Ridao, N
AU  - Ridao N
FAU - Garcia-Ledesma, P
AU  - Garcia-Ledesma P
FAU - Calvo, N
AU  - Calvo N
FAU - Perez-Flores, I
AU  - Perez-Flores I
FAU - Marques, M
AU  - Marques M
FAU - Barrientos, A
AU  - Barrientos A
FAU - Sanchez-Fructuoso, A I
AU  - Sanchez-Fructuoso AI
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Creatinine/blood
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/*adverse effects
MH  - Kidney Transplantation/*immunology
MH  - Male
MH  - Middle Aged
MH  - Pneumonia/*chemically induced
MH  - Protein Kinases/adverse effects
MH  - Sirolimus/*adverse effects/*analogs & derivatives
MH  - TOR Serine-Threonine Kinases
MH  - Transplantation, Homologous/immunology
EDAT- 2009/09/01 06:00
MHDA- 2010/01/12 06:00
CRDT- 2009/09/01 09:00
PHST- 2009/09/01 09:00 [entrez]
PHST- 2009/09/01 06:00 [pubmed]
PHST- 2010/01/12 06:00 [medline]
AID - S0041-1345(09)00733-7 [pii]
AID - 10.1016/j.transproceed.2009.06.003 [doi]
PST - ppublish
SO  - Transplant Proc. 2009 Jul-Aug;41(6):2163-5. doi: 
      10.1016/j.transproceed.2009.06.003.