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Kidney Week

Abstract: PO2200

Successful Management of Chronic Ifosfamide Nephrotoxicity with Immunosuppression: A Case Series

Session Information

  • Onco-Nephrology - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Report

  • 1500 Onco-Nephrology

Authors

  • Malhotra, Sankalp, The Ohio State University, Department of Internal Medicine, Columbus, Ohio, United States
  • Prosek, Jason, The Ohio State University, Department of Internal Medicine, Columbus, Ohio, United States
Introduction

Ifosfamide is an alkylating chemotherapeutic agent that causes both acute and chronic kidney injury. Ifosfamide-induced chronic tubulointerstitial nephropathy can present months after exposure, thereby delaying diagnosis and treatment. Here, we describe three cases of chronic ifosfamide nephrotoxicity, wherein the time-course and outcomes suggest that earlier recognition and initiation of immunosuppression may benefit these patients.

Case Description

Three adult patients with distinct malignancies, status-post at least 3 cycles of ifosfamide chemotherapy, presented to our onco-nephrology clinic for worsening renal function. On average, the patients were referred to our clinic ~8 months after their last dose of ifosfamide. In this period, their serum creatinine (SCr) had risen to a peak ~2.5mg/dL from ~1mg/dL. The patients reported occasional frothy urine but were otherwise asymptomatic. Urine analysis and microscopy was significant for mild glucosuria/proteinuria, sterile pyuria, and granular casts, with urine protein/creatinine ratio of ~1.2. Autoimmune serologies, complement levels, protein electrophoresis, and renal ultrasound were unremarkable. Kidney biopsies, performed 10 months after the last ifosfamide cycle, demonstrated tubulointerstitial nephritis with moderately advanced interstitial fibrosis. Cytologic atypia of the tubular epithelium was consistent with karyomegalic interstitial nephritis (KIN), previously documented in cases of ifosfamide toxicity. In all cases, prednisone therapy led to improvement and plateau of SCr ~2.1. Curiously, multiple attempts to wean corticosteroids led to worsening SCr and active urinary sediment. In 2 patients, addition of mycophenolate mofetil enabled dose reduction but not cessation of corticosteroids. In all cases, SCr remained stable at ~2.1 after 1 year of follow-up.

Discussion

These cases illustrate the latent presentation and challenging management of chronic tubulointerstitial nephritis secondary to ifosfamide. On average, prednisone was started ~10 months after the last ifosfamide dose, when significant interstitial fibrosis had already developed. Delayed therapy and/or enduring inflammation may have also contributed to the failure to stop corticosteroids. Overall, early surveillance, prompt recognition, and long-term immunosuppression is likely important in these patients to stabilize and maintain renal function.