A Pediatric Case of Sirolimus-Associated Pneumonitis After Kidney Transplantation

Abstract

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.

Bronchiolitis obliterans organising pneumonia secondary to tacrolimus toxicity in a pediatric cardiac transplant recipient

“…7 In pediatric solid organ transplant, bronchiolitis obliterans organising pneumonia due to immunosuppressive medications has been only rarely reported. 6 To our knowledge, this is the first reported case of bronchiolitis obliterans organising pneumonia secondary to tacrolimus in a pediatric heart transplant recipient. Our patient was thought to have bronchiolitis obliterans organising pneumonia given the pattern of alveolar involvement seen on the autopsy.…”

“…1,2,3,4 Bronchiolitis obliterans organising pneumonia has mainly been reported, and that too rarely in adult and pediatric Solid organ transplant patients on sirolimus therapy. 5,6 To our knowledge, tacrolimus has not been implicated as a cause of bronchiolitis obliterans organising pneumonia in pediatric heart transplant recipients. We describe a rare case of a 19-month-old cardiac transplant patient who developed bronchiolitis obliterans organising pneumonia in the context of severely elevated levels of tacrolimus.…”

Prognostic value of RGS1 and mTOR Immunohistochemical expression in Egyptian multiple myeloma patients; A single center study

“…Regarding mTOR, Rapamycin was the first mTOR inhibitor, and was initially used as an immunosuppressive drug in the field of solid organ transplantation [ 33 ] . Moreover, there was a strong rationale for mTOR inhibitors (mTORi) effects in many hematological diseases due to the associated hyperactivation of mTOR, as in acute leukemia, lymphoma, multiple myeloma, Waldenström macroglobulinemia, and GVHD [ 22 , 32 ] .…”

“…mTORC is rapamycin sensitive [ 31 ]. Accordingly, Rapalogs (rapamycin and its analogs) was found to induce inhibit the tumor progression by inducing tumor cell apoptosis, cell cycle arrest and signal transduction inhibition in many hematological diseases, one of them is multiple myeloma [ 22 , 32 , 33 ].…”

The Role of mTOR Inhibitors in Hematologic Disease: From Bench to Bedside

“…The mammalian target of rapamycin (mTOR) is a downstream target of multiple signaling pathways involved in biological activities, including the familiar PI3K/Akt/mTOR signaling pathway, which plays an important role in cell growth, differentiation, metastasis and survival, and has become an important target of cancer treatment. Rapamycin (Rapa), the first mTOR inhibitor, was initially used as an immunosuppressive drug in the field of solid organ transplantation ( 1 ). In-depth studies of rapamycin and its analogs (Rapalogs), and of the mTOR signaling pathway, have led to the understanding that Rapalogs can not only induce tumor cell apoptosis, cell cycle arrest and signal transduction inhibition, but that they also affect gene transcription and epigenetic regulation.…”