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Kidney Week

Abstract: PO0293

A Tricky Diagnosis of Complement-Mediated Thrombotic Microangiopathy

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Stone, Fehlin, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
  • Oliver, James D., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
  • Watson, Maura A., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
Introduction

Complement-mediated thrombotic microangiopathy (C-TMA) is caused by inappropriate activation of the alternative complement pathway, usually leading to acute kidney injury (AKI), microangiopathic hemolytic anemia (MAHA), and thrombocytopenia (TCP). Renal biopsy is normally not indicated for diagnosis.

Case Description

A 22 year-old black male was admitted for hypertensive emergency with blood pressure (BP) of 240/140 mmHg, vision loss, and AKI. Ocular exam showed bilateral Frisén Grade IV papilledema. Serum creatinine (sCr) was 4.9 mg/dL (baseline 1.1 mg/dL two years prior) with 4 g proteinuria. Urine microscopy had dysmorphic red blood cells with hyaline and granular casts. Platelet count, hemoglobin, LDH, and haptoglobin were normal. Records showed several years of untreated hypertension; family history was unremarkable. Complement, hepatitis/HIV, ANA, ANCA, anti-GBM, and cryoglobulins were normal. Secondary hypertension workup was negative for endocrine and macrovascular disease. He was treated with antihypertensives and his vision corrected over several days. Renal biopsy showed >50% glomerular obsolescence and 35% interstitial fibrosis/tubular atrophy, with focal arteriolar narrowing and bloodless glomeruli concerning for a subtle TMA. Genetic testing showed a homozygous deletion of CFHR3-CFHR1, confirming C-TMA. Factor H autoantibodies were negative. Therapy was begun with eculizumab, an anti-C5 monoclonal antibody. BP decreased to 120-150/65-90 mmHg and sCr improved to 2.9 mg/dL. He was later switched to ravulizumab for less frequent dosing.

Discussion

This was an atypical presentation of C-TMA without the usual diagnostic clues of TCP or MAHA. Renal biopsy was essential in the eventual diagnosis confirmed by genetic testing. The associations between the genetic variants of C-TMA and specific clinical presentations warrants further investigation.

The views expressed are those of the authors and do not reflect the official policy of the Department of the Army/Navy/Air Force, the Department of Defense or the United States Government.