ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: TH-PO0771

Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits: A Polyclonal Beginning with a Monoclonal Plot Twist

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Yang, Danny, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Saxena, Ramesh, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Introduction

Proliferative Glomerulitis with Monoclonal Immunoglobulin Deposits (PGNMID) is characterized by M protein deposits in glomeruli that cause inflammation and injury by complement activation. The upstream mechanisms of M protein production remain unclear. Less than 30% of cases have detectable M protein or bone marrow clone. Furthermore, it is extremely rare that patients present with an initial polyclonal immune complex mediated glomerulonephritis (PICGN) that subsequently evolves into PGNMID. We herein present 2 cases of membranous PICGN who later developed PGNMID despite immunosuppressive treatment.

Case Description

Patient-1: A 30-year-old man without past medical history presented with acute kidney injury and fluid overload. He had positive antinuclear antibodies with nephrotic syndrome and was found to have a membranous PICGN on biopsy diagnosed as class V lupus nephritis (LN). He was treated with mycophenolate mofetil and steroids with partial remission but developed worsening renal function and recurrent nephrotic syndrome 3 years later. This led to a subsequent kidney biopsy with membranous and crescentic IgG1k PGNMID. He was treated with cyclophosphamide without remission and enrolled in a clinical trial with daratumumab.

Patient-2: A 56-year-old woman with a history of systemic lupus and class V LN suffered a flare of recurrent cerebritis and nephritis. A proliferative and membranous PICGN attributed to lupus was seen on biopsy. She was treated with cyclophosphamide and remained in remission with maintenance immunosuppression, but 5 years later developed worsening proteinuria and renal function. Repeat kidney biopsy showed membranous IgG1k PGNMID. Belimumab was added to her immunosuppressive regimen, and she remains in partial remission.

Discussion

PGNMID is a monoclonal-related histopathological entity that is not only associated with hematolymphoid neoplasms but also with infections, solid tumors, autoimmune diseases and other disorders of persistent antigen exposure. However, transformation of PICGN to PGNMID is rarely described. Two previously described cases had an interval biopsy with polyclonal staining dominant for the eventual culprit monoclonal Ig, suggesting a poly to monoclonal GN evolution. Although the pathogenesis of PGNMID remains unclear, our cases provide more evidence that it can arise from an initial PICGN such as lupus nephritis.

Digital Object Identifier (DOI)