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Kidney Week

Abstract: PO0311

Atypical Hemolytic Uremic Syndrome Secondary to Homozygous CFHR1-CFHR3 Mutation

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Tabbara, Jad, Cleveland Clinic, Cleveland, Ohio, United States
  • Hassanein, Mohamed, Cleveland Clinic, Cleveland, Ohio, United States
  • Wang, Xiangling, Cleveland Clinic, Cleveland, Ohio, United States
  • Anvari, Evamaria, Cleveland Clinic, Cleveland, Ohio, United States
Introduction

Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation characterized by microangiopathic hemolytic anemia, thrombocytopenia, and multisystem end organ damage commonly affecting the kidneys. About two thirds have identifiable genetic abnormalities. Mutations cannot be identified in 30% of the time. A strong association has been observed between anti-FH autoantibodies and a homozygous deletion of CFHR1 and CFHR3. Factor H autoantibodies can impair complement regulation, resulting in aHUS. We report a case of aHUS secondary to a homozygous CFHR1 – CFHR3 mutation.

Case Description

A 35-year-old gentleman with no significant past medical history presented with acute worsening of his kidney function of unclear etiology (creatinine 2.5mg/dL). Kidney biopsy was performed showing thrombotic microangiopathy without evidence of vasculitis. Two days post-biopsy, he developed acute weakness and slurred speech. MRI of the brain was compatible with multiple acute cerebral infarcts. Initial laboratory values were nonspecific but follow up labs showed evidence of hemolysis with worsening renal function (creatinine 3.8 mg/dL) and thrombocytopenia (platelet count 120,000 from 283,000 per microliter). Further workup showed undetectable haptoglobin, elevated lactic acid dehydrogenase, low C3 levels and normal ADAMS-T13 activity. Given high index of suspicion for aHUS and the absence of other causes of thrombotic microangiopathy, he was started on eculizumab. After 6 doses his renal function improved and repeat MRI showed improving cerebral vasculopathy suggesting that the process was likely thrombotic. The aHUS susceptibility panel was positive for a homozygous CFHR3-CFHR1 gene deletion with elevated Factor H autoantibody 74.2 mg/dl (normal 37-68 mg/dl). The patient’s renal function stabilized with complete neurologic recovery. He remains on maintenance dose of eculizumab.

Discussion

Atypical HUS is an rare cause of thrombotic microangiopathy. Many cases have identifiable genetic mutations that lead to dysregulation of alternative complement pathway. Delayed or inappropriately treated cases lead to increased morbidity and mortality. Early screening for aHUS related genetic mutations in patients with acute kidney injury and microangiopathic hemolytic anemia is essential for prompt diagnosis of aHUS and help guide treatment duration.