Everolimus-related pulmonary toxicity in a kidney transplant recipient--diagnosis and management

A standard immunosuppressive regimen after kidney transplantation in a low immunological risk recipient consists of a calcineurin inhibitor (CIN), mycophenolic acid derivative and prednisone. A nephrotoxic effect of CIN and neoplasmatic or cardiovascular history in kidney recipients are the main reasons for a conversion from a CIN to a proliferation signal inhibitor (PSI) [1]. PSI is a novel group of immunosuppressive agents used after solid organ transplantation. Currently, there are two PSIs available, i.e. sirolimus and everolimus. Everolimus (Certican®, Novartis Pharma AG, Basel, Switzerland) is a new PSI/mammalian target of rapamycin (mTOR) inhibitor. Although it is structurally similar to sirolimus, there are a number of important pharmacokinetic differences including a shorter half-life and time to a steady state of everolimus. Both inhibitors of mTOR share a similar side-effect profile, mostly anaemia, dyslipidaemia or proteinuria [2]. The hypersensitivity-like interstitial pneumonitis has mostly been related to sirolimus [3], but there have also been 13 recently published reports of that side effect after everolimus, most of them, however, in heart transplant recipients [8–11,14]. Since the relation in timing between the appearance of pulmonary symptoms and introduction of PSI is variable, the differential diagnosis of such cases could be particularly challenging and it includes a range of pulmonary infections, vasculitis and neoplastic diseases. To illustrate this, we present and discuss a case of pulmonary toxicity (PT) secondary to everolimus in a kidney transplant recipient.