Abstract: FR-PO281
Gemcitabine Hemolytic Uremic Syndrome (HUS) Associated with a New Complement Factor B (CFB) Mutation Successfully Treated with Eculizumab
Session Information
- Onconephrology: From AKI to CKD and Everything in Between
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Lawanto, Stephanie, UMass Chan Med School-Baystate, Springfield, Massachusetts, United States
- Hodgins, Spencer, UMass Chan Med School-Baystate, Springfield, Massachusetts, United States
- Landry, Daniel L., UMass Chan Med School-Baystate, Springfield, Massachusetts, United States
- Mulhern, Jeffrey, UMass Chan Med School-Baystate, Springfield, Massachusetts, United States
- Braden, Gregory Lee, UMass Chan Med School-Baystate, Springfield, Massachusetts, United States
Introduction
Gemcitabine(G) HUS often causes chronic kidney disease or ESRD.We describe a patient(pt) who received a large cumulative dose of G who had a CFB mutation which caused dialysis dependency treated with eculizumab(E) successfully allowing cessation of dialysis.
Case Description
A 46 yr old woman with ER/PR positive & HER/2 negative breast cancer metastatic to her spine, liver and thoracic nodes was given G, 1500 mg on days 1 & 8 of ever 3 week cycle. After receiving 28040 mg/m2 of G she developed a BP of 160/100mmHg, dyspnea,an increase in serum creatinine from 1.3 to 3.7 mg/dl and MAHA with a Hg of 5.4 gm/dl, platelets 100,000, haptoglobin < 10 mg/dl, and LDH of 1046 IU/L & schistocytes on blood smear. C3 & C4 and ADAMTS13 were normal. Hepatitis A B&C, ANA, anti-DNA, cryos, ANCA, Shiga toxin, cardiolipin ab, rheumatoid factor, immunofioxation, INR, PTT, platelet antibodies, DAT, & direct coombs were all normal. After 2 plamaphareses a renal biopsy showed: Light: endothelial swelling, thickening of glomerular basement membranes,with double contours & intraluminal thrombi. IF :no tissue. EM: corrugated basememnt membranes with total foot process fusion and no immune deposits. She rapidly progressed to hemodialysis. Complement gene sequencing (Invitae, San Francisco,CA) showed a CFB mutation c.1937A>C
(p.Tyr646Ser). She then received E 900 mg iv weekly x 4 & 1200 mg every other week for 4 months. MAHA quickly abated & after 3 months dialysis was stopped with a creatinine of 1.8 mg/dl. She died 4 months later from her cancer.
Discussion
We believe G-HUS occurs from a 2 hit hypothesis. G induces apoptosis & cell death in cultured bovine endothelial cells ( AJ van Hall Cell Signal 34:86, 2017).This in the renal vessels coupled with a gain of function mutation in CFB could be enough to induce HUS. Several studies suggest E can treat G-HUS but they did not study complement mutations. Any pt with G-HUS should have complement gene testing performed & if positive E can induce MAHA remission & reverse dialysis dependency.