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Abstract: FR-PO680

Karyomegalic Interstitial Nephritis in a Woman with Hodgkin Lymphoma on Brentuximab Therapy

Session Information

Category: Trainee Case Report

  • 1500 Onco-Nephrology

Authors

  • Patel, Iryna, Los Angeles Biomedical Research institute at Harbor-UCLA Medical center, Torrance, California, United States
  • Nast, Cynthia C., Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Dai, Tiane, Los Angeles Biomedical Research institute at Harbor-UCLA Medical center, Torrance, California, United States
  • Tong, Lili, Los Angeles Biomedical Research institute at Harbor-UCLA Medical center, Torrance, California, United States
Introduction

Karyomegalic interstitial nephritis (KIN) is a rare form of chronic interstitial nephritis that can lead to end stage renal disease. It is characterized histologically by hyperchromatic, abnormally enlarged nuclei of tubular epithelial cells, as well as interstitial fibrosis and tubular atrophy. KIN has an autosomal recessive form, associated with mutations in the FAN1 gene. Other potential etiologies include toxins (e.g. ochratoxin A), heavy metals (e.g. busulfan, lead), alkylating agents (e.g. ifosfamide), and viral infections. We present a case of KIN in a woman with Hodgkin’s lymphoma on brentuximab vedotin (trade name: Adcetris) therapy. To our knowledge, this is the first case report of KIN associated with this medication.

Case Description

A 50 year-old Hispanic female was diagnosed with anaplastic high-grade Hodgkin's lymphoma with metastasis to the liver, large intestine, and adrenal gland. She had poor response to 4 cycles of ABVD (Doxorubicin, Bleomycin, Vinblastine, Dacarbazine) and 3 cycles of ICE (Ifosfamide, Carboplatin, Etoposide). She then received two doses of Brentuximab vedotin. She had a normal renal function prior to the infusion of Brentuximab vedotin, which declined rapidly afterwards. Urinalysis showed 3+ glucose, 3+protein, 1 WBC, 0RBC and 6-10 granular casts/LPF. Urine protein to creatinine ratio was 2.8 g/g. Kidney biopsy showed KIN. Despite discontinuation of brentuximab vedotin, her kidney function continued to worsen, and she was prepared for dialysis.

Discussion

Brentuximab vedotin is an antibody-drug conjugate (ADC) which targets tumor cells expressing CD30, followed by internalization and release of monomethyl auristatin E (MMAE), which binds to tubulin and disrupts the microtubule network. This results in cell cycle arrest, and may explain the markedly enlarged and hyperchromatic nuclei seen in renal tubular epithelial cells, which did not undergo apoptosis as tumor cells do. The present case is the first report of KIN association with brentuximab vedotin. While there is the possibility that KIN may be a late consequence of ifosfamide administration, the temporal relationship between treatment with brentuximab vedotin and the onset of kidney injury suggests that brentuximab vedotin was the most likely responsible agent in this case.