A Rare Case of Membranous Nephropathy in a Patient With Immune-Mediated Necrotizing Myositis: Rituximab Escape
- Glomerular Diseases: Podocytopathies and Nephrotic Syndromes
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1302 Glomerular Diseases: Immunology and Inflammation
- Abuazzam, Farah Shaker Abed, Loma Linda University, Loma Linda, California, United States
- Akram, Sami M., Loma Linda University, Loma Linda, California, United States
- Abdi Pour, Amir, Loma Linda University, Loma Linda, California, United States
- Mathew, Roy O., VA Loma Linda Healthcare System, Loma Linda, California, United States
- Ganesan, Lakshmi, Loma Linda University, Loma Linda, California, United States
- Norouzi, Sayna, Loma Linda University, Loma Linda, California, United States
Rituximab (RTX) has been established as a treatment option for membranous nephropathy (MN). Here, we report a rare case of MN in a patient who was maintained on RTX for the treatment of immune-mediated necrotizing myositis (IMNM).
A 42-year-old male with a history of IMNM, presented with bilateral lower limb edema. He reported frequent IMNM relapses followed by remission with RTX for 10 years as he failed the other immunosuppressive therapies due to serious adverse effects including leukopenia.
On labs, the urine protein creatinine ratio was 7683 mg/g. Glomerular filtration rate by cystatin C was normal. Antinuclear antibodies (ANA) were positive. Complements were normal. Antibodies to double-stranded DNA (dsDNA) and phospholipase A2 receptors were negative. Renal biopsy showed diffuse subepithelial deposits and tubuloreticular inclusions on electron microscopy (EM) (Fig 1) and immunofluorescence staining for IgG and C3. Steroids and tacrolimus were added to RTX for the treatment of the new-onset MN and his condition remains stable.
This is the first report of MN in the setting of RTX-treated IMNM. In our case, MN onset had occurred while the patient was on RTX for a long duration which suggests mechanisms other than B cell depletion may be at work. The presence of another autoimmune disease (IMNM) suggests immune-mediated MN unamenable to RTX. Another possible mechanism is the development of local or low level of antibody formation that would not be peripherally detected as positive dsDNA but may be enough to elicit a local response although the lack of hypocomplementemia, dsDNA, and the characteristic histopathological and clinical systemic lupus features makes lupus nephritis unlikely. This report demonstrates a need for further elucidation of the pathogenesis of secondary MN to improve patient care.
EM: subepithelial deposits in the glomerular basement membrane (arrows)