Selpercatinib-induced renal tubular damage resulting in symptomatic hyponatremia and polyuria: a case report

Selpercatinib is a selective inhibitor of rearranged during transfection (RET) kinase and is indicated for patients with RET fusion-positive non-small cell lung cancer, advanced RET fusion-positive solid tumors, and thyroid cancer. This report describes a patient who developed renal tubular damage resulting in renal loss of electrolytes and polyuria four weeks after the start of selpercatinib. To our knowledge, tubular damage is a rare selpercatinib-induced toxicity. This report contributes to the growing literature about selpercatinib-related adverse events and their management.

A 74-year-old male with RET mutation-positive medullary thyroid cancer, presented with thirst, hyponatremia, hypomagnesemia, hypocalcemia, and polyuria. The hyponatremia deteriorated to symptomatic hyponatremia (112 mmol/L) and required intensive care unit admission. Selpercatinib treatment (160 mg bi-daily) was interrupted, and plasma was collected for therapeutic drug monitoring (TDM). The patient was hospitalized for fluid supplementation and correction of electrolytes. The association with selpercatinib seemed likely due to a Naranjo score of 9 (out of 13). Following dose interruption and supportive care, electrolyte disturbances and polyuria resolved. After recovery, selpercatinib was rechallenged at a dose of 80 mg bi-daily based on TDM. No recurrence of electrolyte disturbances or renal toxicity was observed, and the patient maintained stable disease.

Our report indicates an association between selpercatinib plasma concentration and renal tubular damage, and emphasizes the importance of recognizing selpercatinib-induced tubular injury. This report also provides guidance for the management of these renal manifestations and for rechallenge guided by TDM, highlighting a potential role for TDM in dose determinations after selpercatinib-induced renal toxicity.