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Open Access Highly Accessed Research

Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens

Sean Kirby1, Anjali Satoskar1, Sergey Brodsky1, Amy Pope-Harman2, David Nunley2, Charles Hitchcock1, Ronald Pelletier3, Patrick Ross3, Tibor Nadasdy1 and Konstantin Shilo1*

Author Affiliations

1 Department of Pathology, The Ohio State University Medical Center, Columbus, Ohio, USA

2 Department of Medicine, The Ohio State University Medical Center, Columbus, Ohio, USA

3 Department of Surgery, The Ohio State University Medical Center, Columbus, Ohio, USA

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Diagnostic Pathology 2012, 7:25  doi:10.1186/1746-1596-7-25

Published: 14 March 2012

Abstract

Background

After the introduction of novel effective immunosuppressive therapies, kidney transplantation became the treatment of choice for end stage renal disease. While these new therapies lead to better graft survival, they can also cause a variety of complications. Only small series or case reports describe pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive therapies. The goal of this study was to provide a systematic review of thoracic biopsies in kidney transplant recipients for possible association between a type of immunosuppressive regimen and pulmonary complications.

Methods

A laboratory database search revealed 28 of 2140 renal allograft recipients (18 males and 10 females, 25 to 77 years old, mean age 53 years) who required a biopsy for respiratory symptoms. The histological features were correlated with clinical findings including immunosuppressive medications.

Results

The incidence of neoplasia on lung biopsy was 0.4% (9 cases), which included 3 squamous cell carcinomas, 2 adenocarcinomas, 1 diffuse large B-cell lymphoma, 1 lymphomatoid granulomatosis, and 2 post transplant B-cell lymphoproliferative disorders. Diffuse parenchymal lung disease was identified in 0.4% (9 cases), and included 5 cases of pulmonary hemorrhage, 3 cases of organizing pneumonia and 1 case of pulmonary alveolar proteinosis. Five (0.2%) cases showed histological features indicative of a localized infectious process. Patients on sirolimus had neoplasia less frequently than patients on other immunosuppressive combinations (12.5% vs. 58.3%, p = 0.03). Lung biopsies in 4 of 5 patients with clinically suspected sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding or in combination with other patterns.

Conclusions

Our study documents a spectrum of neoplastic and non-neoplastic lesions in renal allograft recipients on current immunosuppressive therapies. Sirolimus inclusive regimens are associated with increased risk of pulmonary toxicity but may be beneficial in cases of posttransplant neoplasia.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3320012126569395 webcite.

Keywords:
Kidney transplantation; Pulmonary neoplasia; Pulmonary hemorrhage; Mammalian target of rapamycin (mTOR) inhibitors; Sirolimus