{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T12:22:51Z","timestamp":1756902171926,"version":"3.44.0"},"reference-count":42,"publisher":"The Pediatric Pharmacy Association","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020]]},"abstract":"<jats:p>Sirolimus is an immunosuppressive medication often used in solid organ transplantation. It has been associated with severe side effects, including pulmonary toxicity. In adult patients, a single center study found that 14% of those treated with sirolimus developed pulmonary pneumonitis; however, the incidence in the pediatric population is not known. Most reports in adult patients indicate that elevated drug concentrations and a prolonged duration of use are associated with pulmonary toxicity. We report a case of a 17-year-old male kidney transplant recipient who developed rapid-onset respiratory failure, necessitating mechanical ventilation and acute renal replacement therapy for ultrafiltration secondary to sirolimus-induced pneumonitis. He had been treated for acute rejection with corticosteroids 17 days prior to the development of pneumonitis. His symptoms developed within 1 week of initiation of sirolimus and with a serum concentration of 1.1 ng\/mL. Sirolimus was discontinued, and, following aggressive diuresis and ventilatory support, his respiratory status returned to baseline. Sirolimus-induced pneumonitis is an important diagnosis to be considered in any transplant recipient receiving sirolimus with new onset fever, cough, or dyspnea without an identifiable source, especially if there is a preceding history of treatment with high-dose corticosteroids.<\/jats:p>","DOI":"10.5863\/1551-6776-25.5.459","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T21:54:12Z","timestamp":1593554052000},"page":"459-464","source":"Crossref","is-referenced-by-count":2,"title":["A Pediatric Case of Sirolimus-Associated Pneumonitis After Kidney Transplantation"],"prefix":"10.5863","volume":"25","author":[{"given":"Jelte","family":"Kelchtermans","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Glaberson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa","family":"DeFreitas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Alba-Sandoval","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayanthi","family":"Chandar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3883","reference":[{"issue":"10","key":"i1551-6776-25-5-459-b1","series-title":"Nat Rev Immunol","first-page":"599","article-title":"Regulation of innate immune cell function by mTOR","volume":"15","year":"2015","unstructured":"Weichhart\n              T\n            , HengstschlagerM, LinkeM.\n          Regulation of innate immune cell function by mTOR. Nat Rev Immunol. 2015;15(10):599\u2013614."},{"issue":"7","key":"i1551-6776-25-5-459-b2","series-title":"Pediatr Transplant","first-page":"673","article-title":"Sirolimus in pediatric renal transplantation","volume":"15","year":"2011","unstructured":"Kasap\n              B.\n            \n          \n          Sirolimus in pediatric renal transplantation. Pediatr Transplant. 2011;15(7):673\u2013685."},{"issue":"11","key":"i1551-6776-25-5-459-b3","series-title":"Kidney Int","first-page":"1068","article-title":"Sirolimus for calcineurin inhibitors in organ transplantation: contra","volume":"78","year":"2010","unstructured":"Cravedi\n              P\n            , RuggenentiP, RemuzziG.\n          Sirolimus for calcineurin inhibitors in organ transplantation: contra. Kidney Int. 2010;78(11):1068\u20131074."},{"issue":"5","key":"i1551-6776-25-5-459-b4","series-title":"Transplantation","first-page":"787","article-title":"Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients","volume":"72","year":"2001","unstructured":"Morelon\n              E\n            , SternM, Israel-BietD, \n          et al. Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients. Transplantation. 2001;72(5):787\u2013790."},{"issue":"8","key":"i1551-6776-25-5-459-b5","series-title":"Transplantation","first-page":"1215","article-title":"Sirolimus-associated pulmonary toxicity","volume":"77","year":"2004","unstructured":"Pham\n              PT\n            , PhamPC, DanovitchGM, \n          et al. Sirolimus-associated pulmonary toxicity. Transplantation. 2004;77(8):1215\u20131220."},{"issue":"24","key":"i1551-6776-25-5-459-b6","series-title":"N Eng J Med","first-page":"1815","article-title":"Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients","volume":"343","year":"2000","unstructured":"Singer\n              SJ\n            , TiernanR, SullivanEJ.\n          Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients. N Eng J Med. 2000;343(24):1815\u20131816."},{"issue":"4","key":"i1551-6776-25-5-459-b7","series-title":"Mayo Clin Proc","first-page":"541","article-title":"Sirolimus-associated diffuse alveolar hemorrhage","volume":"79","year":"2004","unstructured":"Vlahakis\n              NE\n            , RickmanOB, MorgenthalerT.\n          Sirolimus-associated diffuse alveolar hemorrhage. Mayo Clin Proc. 2004;79(4):541\u2013545."},{"issue":"12","key":"i1551-6776-25-5-459-b8","series-title":"Nephrol Dial Transpl","first-page":"3631","article-title":"Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome\u2014a single-centre experience and review of the literature","volume":"22","year":"2007","unstructured":"Weiner\n              SM\n            , SellinL, VonendO, \n          et al. Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome\u2014a single-centre experience and review of the literature. Nephrol Dial Transpl. 2007;22(12):3631\u20133637."},{"issue":"2","key":"i1551-6776-25-5-459-b9","series-title":"Clin Pharmacol Ther","first-page":"239","article-title":"A method for estimating the probability of adverse drug reactions","volume":"30","year":"1981","unstructured":"Naranjo\n              CA\n            , BustoU, SellersEM, \n          et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239\u2013245."},{"issue":"7","key":"i1551-6776-25-5-459-b10","series-title":"Ann Intern","first-page":"505","article-title":"Brief communication: sirolimus-associated pneumonitis: 24 cases in renal transplant recipients","volume":"144","year":"2006","unstructured":"Champion\n              L\n            , SternM, Israel-BietD, \n          et al. Brief communication: sirolimus-associated pneumonitis: 24 cases in renal transplant recipients. Ann Intern. 2006;144(7):505\u2013509."},{"issue":"4","key":"i1551-6776-25-5-459-b11","series-title":"Pediatr Transplant","first-page":"520","article-title":"Sirolimus in pediatric patients: results in the first 6 months post-renal transplant","volume":"9","year":"2005","unstructured":"Hymes\n              LC\n            , WarshawBL.\n          Sirolimus in pediatric patients: results in the first 6 months post-renal transplant. Pediatr Transplant. 2005;9(4):520\u2013522."},{"issue":"2","key":"i1551-6776-25-5-459-b12","series-title":"J Heart Lung Transplant","first-page":"184","article-title":"Sirolimus immunosuppression in pediatric heart transplant recipients: a single-center experience","volume":"24","year":"2005","unstructured":"Lobach\n              NE\n            , Pollock-BarzivSM, WestLJ, \n          et al. Sirolimus immunosuppression in pediatric heart transplant recipients: a single-center experience. J Heart Lung Transplant. 2005;24(2):184\u2013189."},{"issue":"12","key":"i1551-6776-25-5-459-b13","series-title":"Respir Care","first-page":"1659","article-title":"Sirolimus-induced interstitial pneumonitis in a renal transplant patient","volume":"50","year":"2005","unstructured":"Mingos\n              MA\n            , KaneGC.\n          Sirolimus-induced interstitial pneumonitis in a renal transplant patient. 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Transplant Proc. 2007;39(1):99\u2013102."},{"issue":"1","key":"i1551-6776-25-5-459-b16","series-title":"J Pediatr Gastroenterol Nutr","first-page":"91","article-title":"Interstitial granulomatous pneumonitis associated with sirolimus in a child after liver transplantation","volume":"37","year":"2003","unstructured":"Avitzur\n              Y\n            , Jimenez-RiveraC, FecteauA, \n          et al. Interstitial granulomatous pneumonitis associated with sirolimus in a child after liver transplantation. J Pediatr Gastroenterol Nutr. 2003;37(1):91\u201394."},{"issue":"1","key":"i1551-6776-25-5-459-b17","series-title":"Am J Transplant","first-page":"137","article-title":"Sirolimus-induced pneumonitis: three cases and a review of the literature","volume":"4","year":"2004","unstructured":"Haydar\n              AA\n            , DentonM, WestA, \n          et al. Sirolimus-induced pneumonitis: three cases and a review of the literature. Am J Transplant. 2004;4(1):137\u2013139."},{"issue":"11","key":"i1551-6776-25-5-459-b18","series-title":"Diabetes Care","doi-asserted-by":"publisher","first-page":"3191","DOI":"10.2337\/diacare.26.11.3191","article-title":"Sirolimus-induced interstitial pneumonitis in an islet transplant recipient","volume":"26","year":"2003","unstructured":"Digon\n              BJ\n              3rd\n            ,RotherKI, HirshbergB, \n          et al. Sirolimus-induced interstitial pneumonitis in an islet transplant recipient. Diabetes Care. 2003;26(11):3191. doi:10.2337\/diacare.26.11.3191"},{"issue":"6","key":"i1551-6776-25-5-459-b19","series-title":"Am J Transplant","first-page":"1392","article-title":"BOOP is common in cardiac transplant recipients switched from a calcineurin inhibitor to sirolimus","volume":"5","year":"2005","unstructured":"Lindenfeld\n              JA\n            , SimonSF, ZamoraMR, \n          et al. BOOP is common in cardiac transplant recipients switched from a calcineurin inhibitor to sirolimus. Am J Transplant. 2005;5(6):1392\u20131396."},{"issue":"6","key":"i1551-6776-25-5-459-b20","series-title":"Transplant Proc","first-page":"2830","article-title":"Sirolimus-associated acute respiratory distress syndrome in a renal transplant recipient","volume":"37","year":"2005","unstructured":"Amigues\n              L\n            , KloucheK, MassanetP, \n          et al. Sirolimus-associated acute respiratory distress syndrome in a renal transplant recipient. Transplant Proc. 2005;37(6):2830\u20132831."},{"issue":"6","key":"i1551-6776-25-5-459-b21","series-title":"Transplant Proc","first-page":"2163","article-title":"Sirolimus and everolimus induced pneumonitis in adult renal allograft recipients: experience in a center","volume":"41","year":"2009","unstructured":"Rodriguez-Moreno\n              A\n            , RidaoN, Garcia-LedesmaP, \n          et al. Sirolimus and everolimus induced pneumonitis in adult renal allograft recipients: experience in a center. Transplant Proc. 2009;41(6):2163\u20132165."},{"issue":"2","key":"i1551-6776-25-5-459-b22","series-title":"Ir J Med Sci","first-page":"231","article-title":"Interstitial pneumonitis is a frequent complication in liver transplant recipients treated with sirolimus","volume":"181","year":"2012","unstructured":"Morcos\n              A\n            , NairS, KeaneMP, \n          et al. Interstitial pneumonitis is a frequent complication in liver transplant recipients treated with sirolimus. Ir J Med Sci. 2012;181(2):231\u2013235."},{"issue":"7","key":"i1551-6776-25-5-459-b23","series-title":"Transplant Proc","first-page":"2209","article-title":"Sirolimus conversion experience in a single center","volume":"40","year":"2008","unstructured":"Wang\n              HH\n            , HuangJY, ChuSH, \n          et al. Sirolimus conversion experience in a single center. Transplant Proc. 2008;40(7):2209\u20132210."},{"issue":"11","key":"i1551-6776-25-5-459-b24","series-title":"Ann Am Thorac","first-page":"1912","article-title":"Efficacy and safety of long-term sirolimus therapy for Asian patients with lymphangioleiomyomatosis","volume":"13","year":"2016","unstructured":"Takada\n              T\n            , MikamiA, KitamuraN, \n          et al. Efficacy and safety of long-term sirolimus therapy for Asian patients with lymphangioleiomyomatosis. Ann Am Thorac. 2016;13(11):1912\u20131922."},{"issue":"suppl 1","key":"i1551-6776-25-5-459-b25","series-title":"Exp Clin Transplant","first-page":"170","article-title":"Sirolimus-induced combined posterior reversible encephalopathy syndrome and lymphocytic pneumonitis in a renal transplant recipient: case report and review of the literature","volume":"15","year":"2017","unstructured":"Gheith\n              O\n            , CernaM, HalimMA, \n          et al. Sirolimus-induced combined posterior reversible encephalopathy syndrome and lymphocytic pneumonitis in a renal transplant recipient: case report and review of the literature. Exp Clin Transplant. 2017;15(suppl 1):170\u2013174."},{"issue":"2","key":"i1551-6776-25-5-459-b26","series-title":"J Heart Lung Transplant","first-page":"210","article-title":"Interstitial pneumonitis associated with sirolimus: a dilemma for lung transplantation","volume":"22","year":"2003","unstructured":"McWilliams\n              TJ\n            , LevveyBJ, RussellPA, \n          et al. Interstitial pneumonitis associated with sirolimus: a dilemma for lung transplantation. J Heart Lung Transplant. 2003;22(2):210\u2013213."},{"issue":"6","key":"i1551-6776-25-5-459-b27","series-title":"J Heart Lung Transplant","first-page":"780","article-title":"Fatal interstitial pneumonitis associated with sirolimus therapy in a heart transplant recipient","volume":"23","year":"2004","unstructured":"Manito\n              N\n            , KaplinskyEJ, BernatR, \n          et al. Fatal interstitial pneumonitis associated with sirolimus therapy in a heart transplant recipient. J Heart Lung Transplant. 2004;23(6):780\u2013782."},{"issue":"5","key":"i1551-6776-25-5-459-b28","series-title":"Clin Transplant","first-page":"698","article-title":"Sirolimus-associated interstitial pneumonitis in solid organ transplant recipients","volume":"19","year":"2005","unstructured":"Garrean\n              S\n            , MassadMG, TshibakaM, \n          et al. Sirolimus-associated interstitial pneumonitis in solid organ transplant recipients. Clin Transplant. 2005;19(5):698\u2013703."},{"issue":"9","key":"i1551-6776-25-5-459-b29","series-title":"J Heart Lung Transplant","first-page":"1171","article-title":"Sirolimus-associated interstitial pneumonitis in 3 heart transplant recipients","volume":"25","year":"2006","unstructured":"Delgado\n              JF\n            , TorresJ, Jose Ruiz-CanoM, \n          et al. Sirolimus-associated interstitial pneumonitis in 3 heart transplant recipients. J Heart Lung Transplant. 2006;25(9):1171\u20131174."},{"key":"i1551-6776-25-5-459-b30","series-title":"Respir Med Case Rep","first-page":"8","article-title":"Sirolimus induced granulomatous interstitial pneumonitis","volume":"7","year":"2012","unstructured":"Ussavarungsi\n              K\n            , ElsanjakA, LaskiM, \n          et al. Sirolimus induced granulomatous interstitial pneumonitis. Respir Med Case Rep. 2012;7:8\u201311."},{"issue":"1","key":"i1551-6776-25-5-459-b31","series-title":"Transplant Proc","first-page":"161","article-title":"Sirolimus-induced pneumonitis after renal transplantation: a single-center experience","volume":"44","year":"2012","unstructured":"Lee\n              HS\n            , HuhKH, KimYS, \n          et al. Sirolimus-induced pneumonitis after renal transplantation: a single-center experience. Transplant Proc. 2012;44(1):161\u2013163."},{"issue":"6","key":"i1551-6776-25-5-459-b32","series-title":"Chest","first-page":"1718","article-title":"Sirolimus-induced pulmonary hypersensitivity associated with a CD4 T-cell infiltrate","volume":"129","year":"2006","unstructured":"Howard\n              L\n            , GopalanD, GriffithsM, \n          et al. Sirolimus-induced pulmonary hypersensitivity associated with a CD4 T-cell infiltrate. Chest. 2006;129(6):1718\u20131721."},{"issue":"1","key":"i1551-6776-25-5-459-b33","series-title":"Am J Emerg Med","first-page":"124.e1","article-title":"Acute respiratory distress attributed to sirolimus in solid organ transplant recipients","volume":"33","year":"2015","unstructured":"Wang\n              WL\n            , YuLX.\n          Acute respiratory distress attributed to sirolimus in solid organ transplant recipients. Am J Emerg Med. 2015;33(1):124.e1\u2013124.e4."},{"issue":"2","key":"i1551-6776-25-5-459-b34","series-title":"Clin Kidney J","first-page":"115","article-title":"Oedema, solid organ transplantation and mammalian target of rapamycin inhibitor\/proliferation signal inhibitors (mTOR-I\/PSIs)","volume":"7","year":"2014","unstructured":"Gharbi\n              C\n            , GueutinV, IzzedineH.\n          Oedema, solid organ transplantation and mammalian target of rapamycin inhibitor\/proliferation signal inhibitors (mTOR-I\/PSIs). Clin Kidney J. 2014;7(2):115\u2013120."},{"issue":"10","key":"i1551-6776-25-5-459-b35","series-title":"Transplant Proc","first-page":"3500","article-title":"Switch to everolimus for sirolimus-induced pneumonitis in a liver transplant recipient\u2014not all proliferation signal inhibitors are the same: a case report","volume":"39","year":"2007","unstructured":"De Simone\n              P\n            , PetruccelliS, PrecisiA, \n          et al. Switch to everolimus for sirolimus-induced pneumonitis in a liver transplant recipient\u2014not all proliferation signal inhibitors are the same: a case report. Transplant Proc. 2007;39(10):3500\u20133501."},{"issue":"3","key":"i1551-6776-25-5-459-b36","series-title":"Transplant Proc","first-page":"711","article-title":"Resolution of sirolimus-induced pneumonitis after conversion to everolimus","volume":"38","year":"2006","unstructured":"Rehm\n              B\n            , KellerF, MayerJ, StrackeS.\n          Resolution of sirolimus-induced pneumonitis after conversion to everolimus. Transplant Proc. 2006;38(3):711\u2013713."},{"issue":"12","key":"i1551-6776-25-5-459-b37","series-title":"Am J Transplant","first-page":"2655","article-title":"The multifunctional role of mTOR in innate immunity: implications for transplant immunity","volume":"9","year":"2009","unstructured":"Saemann\n              MD\n            , HaidingerM, HeckingM, \n          et al. The multifunctional role of mTOR in innate immunity: implications for transplant immunity. Am J Transplant. 2009;9(12):2655\u20132661."},{"issue":"5","key":"i1551-6776-25-5-459-b38","series-title":"Nat Rev Immunol","first-page":"324","article-title":"Immunoregulatory functions of mTOR inhibition","volume":"9","year":"2009","unstructured":"Thomson\n              AW\n            , TurnquistHR, RaimondiG.\n          Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol. 2009;9(5):324\u2013337."},{"issue":"16","key":"i1551-6776-25-5-459-b39","series-title":"Blood","doi-asserted-by":"publisher","first-page":"4273","DOI":"10.1182\/blood-2010-09-310888","article-title":"Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells","volume":"117","year":"2011","unstructured":"Weichhart\n              T\n            , HaidingerM, KatholnigK, \n          et al. Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells. Blood. 2011;117(16):4273. doi:10.1182\/blood-2010-09-310888"},{"issue":"6","key":"i1551-6776-25-5-459-b40","series-title":"Immune Netw","first-page":"328","article-title":"Evidence for direct inhibition of MHC-restricted antigen processing by dexamethasone","volume":"14","year":"2014","unstructured":"Im\n              S-A\n            , GerelchuluunT, LeeC-K.\n          Evidence for direct inhibition of MHC-restricted antigen processing by dexamethasone. Immune Netw. 2014;14(6):328\u2013332."},{"issue":"3","key":"i1551-6776-25-5-459-b41","series-title":"Pharmacol Res","first-page":"181","article-title":"Co-administration of sirolimus alters tacrolimus pharmacokinetics in a dose-dependent manner in adult renal transplant recipients","volume":"54","year":"2006","unstructured":"Baldan\n              N\n            , RigottiP, FurianL, \n          et al. Co-administration of sirolimus alters tacrolimus pharmacokinetics in a dose-dependent manner in adult renal transplant recipients. Pharmacol Res. 2006;54(3):181\u2013185."},{"issue":"7","key":"i1551-6776-25-5-459-b42","series-title":"Pediatr Nephrol","first-page":"1119","article-title":"mTOR inhibitors in pediatric kidney transplantation","volume":"29","year":"2014","unstructured":"Pape\n              L\n            , AhlenstielT.\n          mTOR inhibitors in pediatric kidney transplantation. 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