Pulmonary toxicity associated with sirolimus treatment in kidney transplantation

An important side effect of sirolimus, a drug often used in organ transplantation, is pulmonary toxicity.

We present five kidney transplant patients who developed this toxicity associated with sirolimus. All underwent chest radiography computed tomography, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL), microbiological studies of the bronchial aspirate, blood, and sputum, and cytomegalovirus (CMV) polymerase chain reaction (PCR) in blood as well as two had transbronchial biopsies.

All five were men of mean age 54.8 +/- 10.3 years. In two sirolimus formed part of de novo therapy, and three were converted from calcineurin inhibitors. The mean treatment time was 16.6 +/- 13.7 months, with trough levels of 11.3 +/- 3 ng/mL. The patients presented with fever, cough, dyspnea, anemia, and dyslipidemia. The radiological pattern was diffuse alveolointerstitial (n = 2), or bilateral basal interstitial (n = 2), or bilateral basal alveolar (n = 1). The cell count in the BAL was 95% to 99% macrophages. In two patients cultures for bacteria were positive: Hemophilus and Pseudomonas. Tests for fungi, mycobacteria, pneumocystis, and legionella, as well as PCR for CMV were all negative. Transbronchial biopsy yielded insufficient material in one patient and a deposit of fibrinoid material and nonnecrotizing granuloma in the other. Antibacterial therapy was started, three with cotrimoxazole and two with ganciclovir, with no response. The respiratory symptoms improved after withdrawal of sirolimus (mean, 2.4 +/- 1.5 days). The mean hospital stay was 19.8 +/- 14.1 days.

Pulmonary toxicity due to sirolimus should be included in the differential diagnosis of kidney transplant patients who display signs of interstitial pneumonia. Its diagnosis is difficult requiring exclusion of other pulmonary diseases. Resolution of the symptoms was quick after suspension of the drug.