Abstract
Background: As the use and indications of anti-angiogenic therapies such as vascular endothelial growth factor (VEGF) and tyrosine kinases inhibitors (TKI’s) continues to expand, clinicians will be faced with an increase in adverse kidney events associated with these therapies. Focal segmental glomerulosclerosis (FSGS) and thrombotic microangiopathies (TMA) are well recognized kidney pathologies identified in patients receiving anti-angiogenic therapy. Options to treat the nephrotoxicity induced by these agents include discontinuation or dose reduction of the anti-angiogenic therapy or change to alternative agent within the same class of drug. Case presentation: We describe the case of a 74-year-old Caucasian man with metastatic papillary thyroid carcinoma who developed proteinuria and peripheral edema following treatment with Lenvatinib, 20 mg. Kidney biopsy revealed FSGS. Partial resolution of proteinuria (>1.0 g/g) was achieved via temporary discontinuation of Lenvatinib and treatment with oral prednisone. Subsequently, tumor burden increased off Lenvatinib and a collective decision was made to resume this medication at a lower dose. Proteinuria then increased to nephrotic range (>4.0 g/g) following resumption of Lenvatinib, 14 mg. Over the next 3 months the patient went into a complete clinical remission of his nephrotic syndrome following administration of the calcineurin-inhibitor, tacrolimus and permitted ongoing concurrent use of Lenvatinib. Conclusions: Our case demonstrates that low-dose calcineurin inhibitors may have efficacy as a second-line treatment in instances of TKI-induced FSGS. Further studies must be conducted to determine the protective mechanisms of tacrolimus on podocytes from TKIs, however, we hypothesize that calcineurin inhibitors may protect podocytes via downregulation of c-mip, which is overexpressed in the presence of VEGF inhibition and contributes to podocyte cytoskeleton remodeling and subsequent proteinuria.
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