Kidney Week

Abstract: TH-PO685

Breaking Barriers: Unconventional Therapy Treats a Challenging Case of Primary Membranous Nephropathy

Session Information

• Glomerular Diseases: Case Reports - 1
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Hasan, Md Rajibul, Arkansas College of Osteopathic Medicine, Fort Smith, Arkansas, United States

Md Rajibul Hasan, DO

• Abdallah, Ahmed, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Ahmed Abdallah, MD

• Arthur, John M., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

John M. Arthur, MD, PhD, FASN

• Holthoff, Joseph H., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Joseph H. Holthoff, MD, PhD

Introduction

Membranous nephropathy (MN) is a common cause of nephrotic syndrome, occurring either as primary or secondary. Notably, primary MN is linked to specific antigens, such as phospholipase A2 receptor (PLA2R), which is associated with lower rates of spontaneous remission and a progressive decline in kidney function. Approximately 30% of PLA2R-positive cases may exhibit resistance to conventional treatments like rituximab and cyclophosphamide, prompting the need for innovative therapeutic approaches. We hereby, present a case of treatment-resistant primary MN managed using bortezomib, a medication typically used in myeloma therapy.

Case Description

44 y.o. male with past medical history of essential hypertension presented to the emergency department with complains of anasarca for 3 weeks.
On presentation, he had generalized edema on physical exam. Initial laboratory work up revealed a serum creatinine of 2.5 mg/dl (baseline 1.2 mg/dl), serum albumin of <1 g/dl and a urine protein creatinine ratio (UPCR) showed proteinuria of 12.9 g which was later quantified on a 24 hour urinary sample as 15 g. We ordered an anti-PLA2R antibody (IgG) titer which was significantly elevated consistent with primary MN. MN was also evident on renal biopsy that was done prior to the antibody results. He was subsequently started on rituximab infusion but unfortunately failed to respond and had persistently elevated anti PLA2R antibodies. Serum CD-19 was undetectable, however, despite achieving complete B-cell depletion he retained high anti-PLA2R antibody levels. We, therefore anticipated plasma cells lacking CD-19 to be the likely source for persistent production of the culprit antibodies and decided to target plasma cells with bortezumab. After two doses of bortezumab, he achieved a gradual reduction in proteinuria as well as anti PLA2R antibodies.

Discussion

For patients with primary MN who do not attain immunologic remission despite B-cell depletion, another hypothesis proposes the existence of long-lived plasma cells that generate anti-PLA2R antibodies. This rationale led to the administration of the proteasome inhibitor, bortezomib, to our patient with PLA2R-positive MN resistant to rituximab. We suggest targeting plasma cells in specific MN cases that remain immunologically active despite successful B-cell depletion with conventional therapies.