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Abstract: PO1748

Atypical Hemolytic Uremic Syndrome Attributed to Complement Dysregulation in Setting of Metastatic Prostate Cancer Patient

Session Information

Category: Trainee Case Report

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Van Norman, Matthew, University of Texas Health Science Center at Houston, Houston, Texas, United States
  • Mamlouk, Omar, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Workeneh, Biruh, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Introduction

Thrombotic microangiopathy (TMA) is a collection of syndromes, with the most frequent types encountered being hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and atypical HUS. Atypical HUS (aHUS) may be attributed to inherited or acquired complement abnormalities, or secondary causes such as pregnancy, malignancy, transplantation, drugs. Malignancy-associated aHUS is caused by a two-hit event with complement activation playing minor role while in primary aHUS, the primary hit is complement dysregulation. We describe an unusual case of aHUS in a metastatic cancer patient attributed primarily to complement dysregulation.

Case Description

A 64-year old male with history of metastatic prostate adenocarcinoma with spinal involvement presented with a chief complaint of new onset hypertension. He reported dark “coke-colored” urine for one day with intermittent episodes of hematuria. Patient last received chemotherapy with cabazitaxel five months prior. Rest of history and physical exam was unremarkable. Laboratory findings were significant for thrombocytopenia, anemia, and peripheral smear demonstrating schistocytes. Cr peaked at 6.58 mg/dL, ADAMTS13 activity was 100%, and stool PCR was negative for shigella. Complements C3 and C4 were within normal limits. Patient became oliguric with worsening acidosis and was initiated on renal replacement therapy. He underwent a bone marrow biopsy showing no evidence of infiltration of malignancy into the bone marrow. He then had a renal biopsy with pathology showing acute TMA with fibrin thrombi in approximately 50% of the glomeruli. sC5b9 levels were elevated. He was initiated on Eculizumab 900mg once weekly and began to show signs of renal recovery. Within two weeks, he was transitioned off renal replacement therapy.

Discussion

Primary aHUS as a result of complement dysregulation can occur in patients with malignancy. This patient had elevated sC5b9 complex levels with increased alternative pathway activation. He responded to eculuzimab, monoclonal antibody inhibiting activation of C5, with full recovery of his renal function. In cases of aHUS presenting in patients with malignancy, physicians should be aware that aHUS may still occur secondary to the primary hit of complement dysregulation and should consider treatments targeting this complement pathway.