Abstract: PUB188
Is This Primary or Secondary Membranous Nephropathy?
Session Information
Category: Trainee Case Report
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Regmi, Rajan, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Madrid, Bianca, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
Introduction
The definition and management of membranous nephropathy (MN) has rapidly evolved over the past decade, following the identification of PLA2R-Ab. A host of other target antigens have been discovered including thrombospondin type 1 domain-containing 7A, neural epidermal growth factor-like 1, and semaphorin-3B. Primary membranous nephropathy is considered to involve a humoral autoimmune response to a normal podocyte antigen, in the absence of known secondary etiologies including autoimmune diseases, infections, malignancies and certain drugs.
Case Description
We present a 72 Y male with medical conditions including HTN, pre-diabetes, grade 1 obesity, CAD, and remote history of laryngeal cancer, who presents to nephrology clinic for evaluation of lower extremity edema and proteinuria of 11 gms. Labs are consistent with nephrotic syndrome, and he is subsequently started on Furosemide and Lisinopril. His GFR is preserved with serum creatinine of 0.9 mg/dL. Additional work up includes HEP B/C, HIV, SPEP/UPEP/FLC, and ANA, which are negative but PLA2R-Ab is markedly elevated (PLA2R IFA positive with titer of 1:500 and PLA2R ELISA positive at 250.00 RU/mL). The patient refuses renal biopsy. In the absence of a biopsy, a mutual decision is made to treat the patient with rituximab. However, after two doses of rituximab 1g spaced two weeks apart, the patient fails to achieve clinical or biochemical remission within 6 months. The need for a biopsy is again discussed to further determine treatment options, and is eventually done. Biopsy suggests features of secondary MN, including mesangial expansion, intracapillary leucocytes on light microscopy (LM), IgG (1 and 3) and IgM , C3 and C1q deposits, absent PLA2R stain on immunoflourescence (IF), and subepithelial, intramembranous as well as subendothelial electron dense deposits on electron microscopy (EM). A thorough assessment for secondary causes of MN remains unremarkable. A CT head/neck, chest, abdomen, and pelvis is also obtained which does not reveal any malignancy.
Discussion
Although the biopsy findings are suggestive of a secondary MN, the significantly high titer of PLA2R-Ab have persisted. The patient is offered an alkylating agent based therapy, but has opted to enroll in an ongoing clinical trial on anti-CD 38 therapy. He remains under surveillance for possible secondary etiologies due to his biopsy findings, while awaiting his response to anti CD-38 therapy.