Kidney Week 2025 Early Program - Glomerular Diseases: 2025 Update-Clinicopathologic Conference 2: Nephrotic

Video Transcription

Video Summary

The transcript summarizes a clinicopathologic conference (CPC) featuring three real-world kidney cases to highlight diagnostic dilemmas in nephrotic and glomerular diseases.

<strong>Case 1:</strong> A 66-year-old man presented with edema, acute kidney injury on CKD, and severe nephrotic syndrome (15 g/day proteinuria, albumin ~1.9). Serologic and infectious workup was negative, and PLA2R staining was negative. Biopsy workup suggested <strong>membranous nephropathy</strong> (granular capillary wall Ig staining; EM deposits), prompting discussion of additional antigen testing in PLA2R-negative disease (e.g., NELL1, THSD7A). The case included consideration of associated malignancy risk and treatment decisions balancing cancer concerns with the immediate danger of nephrotic complications.

<strong>Case 2:</strong> A premature infant (3 weeks old) developed congenital nephrotic syndrome after a pregnancy complicated by chorioamnionitis. The discussion emphasized that most nephrotic syndrome presenting in the first months of life is genetic (e.g., NPHS1, NPHS2, LAMB2, WT1), so initial management focused on complications (edema control, infection/thrombosis risk) and rapid genetic/infectious evaluation rather than biopsy. When the child worsened at 6 months and genetics were negative, biopsy revealed <strong>collapsing glomerulopathy</strong> with <strong>tubular reticular inclusions</strong>, suggesting a high-interferon/viral-associated process; despite extensive testing, no specific infection was found, and the child progressed toward kidney failure.

<strong>Case 3:</strong> A 55-year-old woman with CKD and nephrotic-range proteinuria had multiple positive autoantibodies (P-ANCA/MPO, ANA, dsDNA) but normal complements and negative PLA2R. Biopsy showed <strong>fibrillary glomerulonephritis</strong> (random fibrils on EM; <strong>DNAJB9-positive</strong>), illustrating how misleading serologies can be. Treatment options were limited; partial improvement occurred with immunosuppression/supportive therapy, and rituximab data show modest remission rates.

Asset Subtitle

Shane A. Bobart, Agnes B. Fogo, Nelson Leung, Laura H. Mariani, Kristin Meliambro, Michelle N. Rheault, Joshua M. Thurman

Meta Tag

Module GLOM

Speaker FACULTY FACULTY

Keywords

clinicopathologic conference

nephrotic syndrome

glomerular disease

membranous nephropathy

PLA2R-negative membranous nephropathy

NELL1 antigen

THSD7A antigen

congenital nephrotic syndrome genetics

collapsing glomerulopathy tubular reticular inclusions

fibrillary glomerulonephritis DNAJB9