Abstract: SA-PO205
Cryoglobulinemic Thrombotic Microangiopathy: A Subtype of Monoclonal Gammopathy of Renal Significance
Session Information
- Onconephrology: Immunological Cross-Talk
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Ling, Andrew, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Mistry, Kavita, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Padmanabhan, Shanmugha Vigneshwar, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Lecker, Stewart H., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Riella, Cristian, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- William, Jeffrey H., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
Introduction
Monoclonal gammopathy of renal significance (MGRS) encompasses a set of disorders in which a cell clone secretes immunoglobulin that causes kidney damage without meeting criteria for a malignant plasma cell dyscrasia. These conditions often involve damage mediated by direct monoclonal Ig deposition, though less commonly include processes like thrombotic microangiopathy (TMA) without direct antibody deposition in the kidney. Here, we present a case of kidney injury secondary to a cryoglobulin-mediated TMA responsive to steroids and clone-directed therapy.
Case Description
A 45-year-old African American woman with recent COVID-19 infection presented with weakness. Vital signs and exam were unremarkable. Labs were notable for creatinine of 8.3 mg/dL, hemoglobin 7.6 g/dL, platelet count 121 K/µL, and LDH 439 IU/L. Urinalysis revealed 4+ blood and 4+ protein with >182 RBC/hpf and muddy brown casts. PLASMIC score was 4. ADAMTS13 activity and functional TMA panel were normal. SPEP/UPEP showed monoclonal IgG lambda. Renal biopsy revealed chronic thrombotic microangiopathy. With a cryocrit of 2.5%, biopsy findings were most consistent with a cryoglobulinemic TMA with absence of paraprotein or immune deposits. She was discharged with a prolonged course of corticosteroids with clinical improvement.
Six months later, she re-presented with recurrent AKI (creatinine 3.1 mg/dL), anemia, and thrombocytopenia. Renal function continued to worsen with repeat pulse-dose corticosteroids. Plasmapheresis and clone-directed therapy with bortezomib resulted in dramatic improvement in renal function (creatinine 1.1 mg/dL).
Discussion
Thrombotic microangiopathy is a less common manifestation of monoclonal gammopathy of renal significance and even more rarely associated with Type I cryoglobulinemia. This case demonstrates a paraprotein-mediated process causing disordered complement regulation leading to a TMA. To our knowledge, this is only the second reported case of severe acute kidney injury caused by a cryoglobulinemic thrombotic microangiopathy that was successfully treated with plasma exchange and clone-directed therapy. The role of these therapies in cryoglobulinemic TMA as well as consideration of eculizumab as a subsequent line of therapy in refractory cases merits ongoing discussion.