Focal Segmental Glomerulosclerosis with Acute Renal Failure Associated with Eltrombopag Therapy

Abstract

Eltrombopag, a small‐molecule nonpeptide agonist of the thrombopoietin receptor, is used for treatment of thrombocytopenia of various causes, including chronic idiopathic thrombocytopenic purpura (ITP) and hepatitis C‐related liver cirrhosis. During clinical trials, eltrombopag was discontinued in three patients due to ascites, neutropenia, and retinal exudates. Another recently reported major adverse event was reversible acute renal failure in a patient with antiphospholipid syndrome; nephrotoxicity caused by eltrombopag was highly suspected, but a kidney biopsy was not performed. We describe a 46‐year‐old woman with a history of mitral valve prolapse who had an incidental finding of an isolated low platelet count of 22 × 103/mm3. A tentative diagnosis of ITP was made, and oral prednisolone 25 mg twice/day was started. Despite prednisolone dosage adjustments over the next several weeks, her platelet count remained at 15–40 × 103/mm3, and oral eltrombopag 75 mg/day was begun. After seven doses, the patient came to the emergency department with persistent nausea and vomiting. Laboratory work‐up revealed renal failure, and eltrombopag was discontinued. The patient was hospitalized, and on day 2, her renal failure had progressed, and proteinuria was detected. On day 6, emergency hemodialysis was begun. A complete blood count on day 21 revealed progression of anemia and thrombocytopenia. Splenectomy was performed on day 35, which successfully reversed her thrombocytopenia. She was discharged on day 39, and hemodialysis was discontinued on day 44. At follow‐up on day 56, the patient's platelet count was within normal limits. On day 70, kidney biopsy results revealed a typical pattern of focal segmental and diffuse global glomerulosclerosis. By day 210, her ITP had resolved, and her renal function was stable. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of acute renal failure and eltrombopag therapy. To our knowledge, this is the first case report of a patient who experienced acute renal failure and proteinuria concomitant with a pathology of focal segmental glomerulosclerosis after treatment with eltrombopag. This report of a serious case of reversible renal failure after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before commencing with more extensive clinical use in the future.