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Abstract: TH-PO100

Complement-Mediated Hemolytic Uremic Syndrome Presenting With Nephrotic Range Proteinuria

Session Information

  • AKI: Mechanisms - I
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Singh, Aditi, UConn Health, Farmington, Connecticut, United States
  • Simeone, Stephen N., UConn Health, Farmington, Connecticut, United States
  • Jweehan, Duha A., UConn Health, Farmington, Connecticut, United States
  • Shah, Mamta, UConn Health, Farmington, Connecticut, United States
Introduction

Complement-mediated hemolytic uremic syndrome (CM-HUS) has a varied clinical presentation and diagnosis remains one of exclusion. We present a case of thrombotic microangiopathy (TMA) secondary to CM-HUS presenting with hematuria and nephrotic range proteinuria without underlying glomerulonephritis (GN).

Case Description

A 45-year-old male presented with a three-day history of dark brown urine. Work-up revealed acute kidney injury (AKI) with a serum creatinine of 1.6 mg/dL from a baseline of 0.9 mg/dL, hemoglobin of 10.1 g/dL and a platelet count of 19,000 platelets/µL. Haptoglobin was <8 mg/dL and peripheral blood smear showed 7 schistocytes per high-power field. Urinalysis depicted large hemoglobin with 10-15 red blood cells and 24-hour urine protein collection had nephrotic range proteinuria at 3 grams. Given suspicion for thrombotic thrombocytopenic purpura, plasma exchange (PEX) was initiated however this was discontinued after ADAMTS13 was found to be 63%. Despite improvement in his hemoglobin and platelet counts, proteinuria persisted and extensive evaluation for an autoimmune, infectious or hematologic etiology was negative. Renal biopsy findings were consistent with glomerular TMA (Figure 1) without evidence of underlying GN or IgA nephropathy. High dose steroids were administered with resolution of his AKI and proteinuria. Genetic testing demonstrated heterozygosity for CD46 and PLG variants of CM-HUS.

Discussion

TMA with proteinuria is associated with comorbid GN or systemic vascular diseases such as systemic lupus erythematosus. This case of CM-HUS is unique in its presentation of proteinuria without associated GN. There are few such reported cases of CM-HUS in children and they describe a resolution of proteinuria following PEX and eculizumab treatment. The mechanism of proteinuria in CM-HUS is poorly defined however endothelial injury or podocytopathy could be suspected.

Capillary loop with endothelial cell lift off of glomerular basement membrane with fluffy amorphous deposit in subendothelium