Everolimus-induced nephrotic syndrome precipitated by interaction with voriconazole in a patient with Hodgkin's lymphoma.

WHAT IS KNOWN AND

OBJECTIVES

Everolimus is a small molecule that inhibits the mammalian target of rapamycin (mTOR) and is used for treatment of various solid tumours and renal transplant rejection prophylaxis. Whereas everolimus-induced proteinuria was previously observed in 3%-36% renal transplant recipients, nephrotic syndrome was not reported in cancer patients taking everolimus. However, nephrotic syndrome was reported in patients taking sirolimus.

CASE SUMMARY: We report the case of a 32-year-old female with relapsed Hodgkin's lymphoma who was on everolimus for 5 years and developed nephrotic syndrome about 2 months after initiation of voriconazole. She was on 10 mg everolimus once a day and 200 mg voriconazole twice a day orally. Renal biopsy revealed thrombotic microangiopathic vasculopathy and thin basement membrane nephropathy. Discontinuation of everolimus and voriconazole rapidly improved her nephrotic syndrome.

WHAT IS NEW AND

CONCLUSION

We provide in-depth analysis of the underlying mechanisms of everolimus-induced nephrotic syndrome and hypothesize that voriconazole likely decreased everolimus metabolism. In the era of targeted therapy for cancer, healthcare providers should be aware of the drug-drug interaction between everolimus (as well as tyrosine kinase inhibitors) and cytochrome P450 CYP3A4 inhibitors (ie voriconazole).