EXT2 transition in adolescent membranous nephritis

Area of Science:

• Nephrology
• Immunology
• Pediatric Nephrology

Background:

• Membranous nephropathy (MN) is a significant cause of nephrotic syndrome in children, with rising incidence in adolescents.
• Traditionally classified as primary or secondary, MN is now increasingly characterized by specific antigens.
• Antigen identification in MN aids in understanding underlying conditions, prognosis, and treatment options.

Purpose of the Study:

• To report a unique case of an adolescent with membranous nephropathy (MN).
• To describe the diagnostic challenges and evolution of MN antigen detection.
• To illustrate the potential for developing other kidney diseases, such as lupus nephritis, despite initial negative antigen status.

Main Methods:

• Case report of an adolescent patient with nephrotic syndrome.
• Kidney biopsy analysis for membranous nephropathy (MN) and associated antigens (PLA2R, NELL1, THSD7A, EXT2).
• Monitoring of clinical presentation and treatment response, including B-cell depleting therapy and repeat biopsy.

Main Results:

• The patient initially presented with MN negative for PLA2R, NELL1, THSD7A, and EXT2, responding to B-cell depletion.
• Three years later, the patient developed proliferative lupus nephritis alongside ongoing membranous nephritis.
• A subsequent kidney biopsy revealed newly detected EXT2-positive deposits, indicating a discordant antigen result over time.

Conclusions:

• This case demonstrates that membranous nephropathy (MN) antigen detection can appear to change over time.
• EXT1/2 negativity in initial MN biopsies does not preclude the later development of lupus nephritis in adolescents.
• The findings underscore the complexity of MN diagnosis and the importance of longitudinal monitoring.