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Kidney Week

Abstract: PO2201

Hyperphosphatemia in the Setting of Fibroblast Growth Factor Receptor Inhibitors

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

  • Zonoozi, Shahrzad, Pennsylvania Hospital, Philadelphia, Pennsylvania, United States
  • Kfoury, Bader, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Geara, Abdallah Sassine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States
Introduction

Fibroblast growth factor (FGF)-23 is a phosphaturic hormone which works by reducing apical membrane expression of sodium-phosphate co-transporters in the proximal renal tubule and thus decreasing phosphate re-absorption. Fibroblast growth factor receptors (FGFR) are ubiquitously expressed in different tissues and become altered in various types of cancer. TAS-120 is one of several pan-FGFR inhibitors currently in clinical trials for use in patients with cholangiocarcinoma. Hyperphosphatemia is seen in more than 70% of patients on this therapy.

Case Description

A 44-year-old female with metastatic intrahepatic cholangiocarcinoma with progressive disease despite conventional therapy was started on TAS-120. Fifteen days into treatment she developed pain in knees and hips and was noted to be hyperphosphatemic to 7 mg/dL. She was initiated on sevelemer but given persistent hyperphosphatemia to 6.4 mg/dL, acetazolamide, calcitonin and phytonadione were added. Despite this, phosphorus remained elevated at 5.8 mg/dL; addition of alendronate 35mg weekly alongside dose reduction of TAS-120 led to sustained improvement in serum phosphorus levels.

A 49-year-old male with a history of cholangiocarcinoma was started on TAS-120. Four days into treatment he developed calf pain and was noted to be hyperphosphatemic to 7.3 mg/dL. The medication was briefly stopped and he was initiated on sevelamer with improvement in phosphorus to 2.7 mg/dL. Resumption of TAS-120 led to recurrent hyperphosphatemia for which acetazolamide was initiated. Three months after initiation of TAS-120 he had ongoing hyperphosphatemia; following dose reduction of TAS-120 and starting phytonadione, probenecid and calcitonin, serum phosphorus levels remained within normal limits.

Discussion

FGFR-induced hyperphosphatemia has a similar clinical presentation as hyperphosphatemic familial tumoral calcinosis (HFTC) with debilitating join pain and tissue calcification. The current management of hyperphosphatemia relies mainly on dietary modification and gastrointestinal phosphate binding that were insufficient for our patients. The hyperphosphatemia and calciphylaxis pain was successfully treated with phosphaturic medications (acetazolamide, calcitonin) and alendronate. Phytonadione (vitamin K) interferes with matrix Gla protein, a tissue inhibitor of calcification.