Abstract: PUB543
Severe Microangiopathic Anemia in an ESRD Patient Unmasks Complement-Mediated Atypical Hemolytic-Uremic Syndrome (aHUS) and Successful Management with Treatment of aHUS
Session Information
Category: Trainee Case Report
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Punj, Shweta, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
- Chang, Anthony, UChicago Medicine, Chicago, Illinois, United States
- Aggarwal, Vikram, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
Introduction
Anemia amongst ESRD patients is mostly due to erythropoietin deficiency and disordered iron metabolism. We present an ESRD patient with severe complement-mediated hemolytic anemia due to aHUS. Identification of genetic abnormalities in complement regulatory proteins and use of complement inhibitors lead to successful resolution of near-fatal anemia. We posit that the underlying cause for ESRD might be related to aHUS presenting as ANCA-negative vasculitis.
Case Description
A 39-year old African-American female patient with ESRD was admitted for severe symptomatic anemia and need for red-blood cell transfusion despite erythropoietin-stimulating agents (ESA). She was evaluated a year prior for chronic kidney disease with a nephritic presentation. Serological evaluation was negative. Kidney biopsy reported as pauci-immune ANCA-negative glomerulonephritis with significant chronicity. Given renal-limited vasculitis and chronicity, she didn’t receive immunosuppressives. Hemoglobin & renal function remained stable. Blood pressure was controlled with ACE-I. eGFR dropped in 4 months with a decline in hemoglobin and platelet count, needing dialysis and ESA initiation. Severe, transfusion-requiring anemia workup showed elevated LDH and reticulocyte count, undetectable haptoglobin, increased schistocytes and thrombocytopenia. She was started on Eculizumab for aHUS without plasmapheresis. Hemoglobin improved within 2 weeks and eventually normalized while on Eculizumab. Genetic testing for aHUS showed multiple, heterozygous, missense variants of complement factor H (CFH). Prior renal biopsy showed changes of arteriolopathy that cemented concerns for aHUS. She remains transfusion-independent and on Eculizumab.
Discussion
CFH mutations are the commonest amongst genetic causes for aHUS. In African-American patients, CFH variants might be just as impactful in causing CFH-related GN and ESRD. Our patient had hemolytic anemia due to complement-mediated aHUS with brisk response to Eculizumab. Testing reveals her genetic predisposition to aHUS with multiple CFH variants, common amongst ESRD patients of African-American ancestry. Besides being a rare cause for anemia in ESRD patients, we propose that complement-mediated aHUS might have been the original cause for ESRD in this patient.