Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sirolimus (Rapamune; Wyeth-Ayerst, Philadelphia, PA) is a newer immunosuppressive drug with no known acute or chronic nephrotoxic effects; however, limited data are available in liver transplant recipients. We prospectively evaluated changes in renal function in liver transplant recipients after conversion from a calcineurin inhibitor to sirolimus monotherapy. We measured serial serum creatinine levels in liver transplant recipients with chronic nephrotoxicity caused by calcineurin inhibitors before and after conversion to sirolimus therapy. Estimated glomerular filtration rate (eGFR) was calculated from the Modification of Diet in Renal Disease formula. Change in eGFR over time, incidence of acute hepatocellular rejection, and adverse events while being administered sirolimus monotherapy were recorded. Mean interval between liver transplantation and initiation of sirolimus therapy was 310 weeks (range, 9 to 780 weeks). Of 21 patients included in our study, 18 patients were converted to sirolimus monotherapy and 3 patients were switched to sirolimus and low-dose steroid therapy. Patients were followed up for a mean of 66.8 +/- 38.9 (SD) weeks after conversion. Renal function improved in 71% of patients (15 of 21 patients). Median eGFR improved significantly from 34 mL/min/1.73 m2 at the time of conversion to 43 mL/min/1.73 m2 at the last follow-up (27% increase in eGFR; P = 001). Median monthly change in eGFR was from -0.25 mL/min/1.73 m2 pre-sirolimus therapy to +1.28 mL/min/1.73 m2 post-sirolimus therapy (P =.09). Adverse events were mostly mild and self-limited. Only 1 patient developed biopsy-proven acute cellular rejection, which was treated with sirolimus and mycophenolate mofetil. Two patients discontinued sirolimus therapy because of toxicity (oral ulceration, 1 patient; interstitial pneumonitis, 1 patient). Renal function improved significantly in the majority of liver transplant recipients with renal insufficiency caused by calcineurin inhibitors when converted to sirolimus therapy. Sirolimus monotherapy provided adequate immunosuppression with a low incidence of acute cellular rejection and minimal adverse events.
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PMID:Renal function improves in liver transplant recipients when switched from a calcineurin inhibitor to sirolimus. 1452 3

Sirolimus is a recently licensed immunosuppressant for organ transplantation that has been used as basic, adjuvant, or maintenance therapy for prevention of organ rejection. Well-known side effects of this agent are hyperlipidemia and bone marrow suppression. Interstitial pneumonitis is a relatively newly described adverse effect of the drug. A 43-year-old female recipient of a cadaveric kidney developed cough with blood-tinged sputum while receiving sirolimus immunosuppressive therapy. High-resolution computed tomographic scan and chest radiograph revealed interstitial infiltrations over bilateral lower lungs. No evidence of bacterial, fungal, mycobacterial, or viral infection was found and all tests for collagen vascular diseases were negative. Discontinuation of sirolimus resulted in a significant improvement of the lung disease.
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PMID:Sirolimus-induced interstitial pneumonitis in a renal transplant recipient. 1536 50

Sirolimus is a promising immune suppressive agent, with the potential to reduce calcineurin inhibitor associated nephrotoxicity, halt progression of chronic rejection and prevent tumor proliferation. The aim of this study was to review the experience using sirolimus in pediatric liver transplant recipients at a single center. Database and medical charts of all pediatric liver transplant recipients receiving sirolimus at the Hospital for Sick Children in Toronto were reviewed. Eight patients received sirolimus between October, 2000 and September, 2002. Indications for using sirolimus were post-transplant lymphoproliferative disease (PTLD) (n = 6) and hepatoblastoma (n = 2). Two patients with PTLD concurrently had renal impairment and chronic rejection. Sirolimus dosages ranged between 1.5 and 5 mg once daily. Median duration of follow-up was 17 months. Persistently elevated liver transaminase levels in the two children with chronic rejection decreased during sirolimus therapy. Recurrence of PTLD occurred in one patient. Two patients were diagnosed with acute cellular rejection after transition to maintenance sirolimus monotherapy. Resolution of adverse effects including mouth sores (n = 3), leg swelling (n = 2) and hyperlipidemia (n = 3) occurred either spontaneously or with dose reduction. Sirolimus was discontinued in four patients because of persisting bone marrow suppression, interstitial pneumonitis, life-threatening sepsis and refractory diarrhea. Children with PTLD or hepatoblastoma may benefit from immune suppression with sirolimus after liver transplantation. Further multi-center, prospective, randomized controlled trials will be instrumental to further the knowledge of long-term efficacy, safety and tolerability of sirolimus for selected children following liver transplantation.
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PMID:Sirolimus for pediatric liver transplant recipients with post-transplant lymphoproliferative disease and hepatoblastoma. 1517 61

Sirolimus is an immunosuppressive drug which has proved its effectivity to reduce the incidence of acute rejection in renal transplantation receptors. As this drug lacks nephrotoxic effects, its simultaneous use with other anticalcineurinic drugs allows the use of reduced doses. Thrombocytopenia and hyperlipidemia are the best known side-effects of sirolimus administration. Alterations in hepatic biochemistry results are also common. Some instances of interstitial pneumonitis associated to its use have been recently reported. In this paper we present a clinical case related to this rare but already confirmed adverse side-effect, which apart from the other more common nosologies occurring in immunosuppressed patients, should be taken into account in the differential diagnosis of interstitial pneumonitis in patients who are being administered this drug.
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PMID:[Interstitial pneumonitis associated with sirolimus administration in a renal transplantation patient: a clinical case]. 1521 60

Opportunistic infection is a major threat to immunocompromised patients. However, infection due to Mycobacterium xenopi is rare in renal transplant recipients. We report two new cases of M. xenopi pulmonary infection (one case of interstitial pneumopathy and one of a pulmonary nodule) in renal transplant recipients, detected in the same center at an interval of a few months. Both patients were on an immunosuppressive regimen including a recent switch to sirolimus. Sirolimus is a new immunosuppressive drug already known to be responsible for interstitial pneumonitis. It also inhibits interleukin-12-induced proliferation of activated T lymphocytes, which is critical for the development of the cell-mediated immunity that protects against mycobacteria. These two case reports suggest that sirolimus therapy may lead to an impairment of the immune response against intracellular pathogens such as M. xenopi.
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PMID:Mycobacterium xenopi pulmonary infection in two renal transplant recipients under sirolimus therapy. 1576 36

Sirolimus inhibits human fibroblast cell proliferation in cell cultures from transbronchial biopsies of lung transplant recipients. However, a few cases of interstitial pneumonitis and bronchiolitis obliterans organizing pneumonia have been recently described in solid organ transplant recipients, including a fatality in a heart transplant recipient. We studied the patterns of pulmonary adverse effects associated with sirolimus in 4 renal transplant recipients who developed pulmonary opacities on chest radiograph, which were proved to be noninfectious in origin. Lung biopsy was performed to obtain histological diagnosis (3 interstitial pneumonitis, 1 necrotizing vasculitis). Symptoms were dyspnea (4), cough (2), hemoptysis (1), fever (1) and eyelid edema (1). Those with interstitial pneumonitis had bilateral basal opacities on chest X-ray, and histopathology showed mild lymphoplasmocytic interstitial inflammation, scattered intraalveolar epitheloid granulomas and a focal pattern of organizing pneumonia. Serum C-reactive protein (CRP) was elevated and bronchoalveolar lavage revealed lymphocytosis (77, 79.5 and 31%). The fourth patient had an opacity localized in the upper lobe, which progressed to both the lower lobes, and histopathology showed multifocal necroses of lung tissue with lymphoplasmocytic vasculitis and scattered granulomas. In this patient, the serum CRP level was not elevated and bronchoalveolar lavage was normal. Pulmonary symptoms and opacities on chest radiograph resolved and the serum CRP level became normal after sirolimus was stopped in all patients. Sirolimus may be a cause of interstitial pneumonitis or pulmonary vasculitis, and withdrawal of sirolimus is therapeutic.
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PMID:Patterns of pulmonary complications associated with sirolimus. 1716 40

Sirolimus is a new potent immunosuppressive drug used in organ transplantation; its major advantage is the absence of deterioration in renal function. Documented adverse effects include myelosuppression and hyperlipidemia. Recently several cases of sirolimus-associated interstitial pneumonitis have been reported, usually of mild severity. We report a new case that was complicated by a severe acute respiratory distress syndrome, which required several days of mechanical ventilation. No infectious or cardiogenic etiology was documented. Low sirolimus blood levels and acute CD4 lymphocytic alveolitis suggested an immune-related mechanism rather than a direct toxic effect of the drug. The patient recovered after discontinuation of sirolimus and the administration of corticosteroids.
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PMID:Sirolimus-associated acute respiratory distress syndrome in a renal transplant recipient. 1618 23

We report a series of 26 heart transplant recipients with renal impairment in which sirolimus was used as the basic immunosuppresive drug (without associated calcineurin inhibitors) to avoid further nephrotoxicity. Sirolimus (trough levels 10 to 12 ng/mL, average daily dose 3 mg) was used in two settings: de novo in 7 patients with significant preexistent renal impairment and as a chronic conversion in 19 stable patients with established renal failure (creatinine level >2 mg/dL). In all de novo patients (n = 7), the renal function significantly improved. Creatinine fell from 2.95 +/- 0.9 mg/dL to 1.41 +/- 0.4 mg/dL at follow-up (P = .0017). One patient died suddenly of a massive pulmonary embolism. Only one patient experienced histologic but reversible rejection. In one patient, anemia and diarrhea prompted sirolimus withdrawal. Five patients had infectious episodes: three bacterial pneumonias, one mediastinitis, and two CMV infections. In the chronic conversion group (n = 19), the improvement was mostly limited to patients with moderate renal failure (creatinine < or =2.5 mg/dL) in which creatinine fell from 2.24 +/- 0.2 to 1.9 +/- 0.27 mg/dL, P = .009). When basal creatinine was over 2.5 mg/dL, only one third of the patients improved after conversion. Two patients died: terminal renal failure and cerebrovascular accident. There were no clinical episodes of rejection. Secondary effects prompted the discontinuation of sirolimus in five patients: two definite and one possible interstitial pneumonitis and two cases of anemia). The symptoms resolved after sirolimus withdrawal. Six patients had infection: four pneumonias, one sepsis, and one cutaneous abscess. Sirolimus is an interesting alternative to calcineurin inhibitors in selected patients with renal impairment. It prevents renal failure in de novo recipients at high risk of catastrophic renal damage and ameliorates renal dysfunction in chronic patients with moderate renal dysfunction. Given the high incidence of secondary effects, the adequate dosage and the secondary effects profile needs further study.
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PMID:Sirolimus as an alternative to anticalcineurin therapy in heart transplantation: experience of a single center. 1638 15

Sirolimus (rapamycin) and everolimus are immunosuppressive agents that inhibit cardiac allograft vasculopathy. Sirolimus has been widely used in renal transplantation, and its use in heart transplantation is increasing. Sirolimus-associated pneumonitis has been described in renal transplant patients. Two cases of sirolimus-associated pneumonitis have been reported after cardiac transplantation. Only 1 case has been described in detail, and this had a fatal outcome. Here, we present a case of sirolimus-associated interstitial pneumonitis in a cardiac transplant recipient that resolved completely with withdrawal of the drug and treatment with corticosteroids.
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PMID:Reversible sirolimus-associated pneumonitis after heart transplantation. 1681 33

This retrospective study aimed to evaluate the benefit of switching from calcineurin inhibitors (CnI) to sirolimus in posttransplant Kaposi's sarcoma (KS). Fourteen patients monitored in five French departments who had developed posttransplant KS were switched from CnI to sirolimus either abruptly (n=9) or progressively (n=5) with trough levels 5-12 ng/mL. Two patients had a complete remission, eight a partial response, and five no significant improvement of KS. The mean time to response was 3.9 months. After a mean follow-up of 16 months, 3 partial responders, with previous severe and refractory KS, suffered again from KS progression despite the lack of concomitant infectious or neoplastic event. These relapses occurred 5-9 months after switching. The tolerance of sirolimus has been excellent except for in one patient who developed severe interstitial pneumonitis. Sirolimus is usually useful in the management of posttransplant KS. It may be, however, ineffective or transiently effective in some patients with severe KS. Prospective studies with pharmacodynamic evaluation are important in order to better assess the duration of responses and the mechanisms of primary and acquired drug resistance.
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PMID:Sirolimus conversion for patients with posttransplant Kaposi's sarcoma. 1678 May 49


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