Kidney Week

Abstract: TH-PO0353

COL4A3-Associated Alport Spectrum Disease Misdiagnosed as Primary FSGS After Pregnancy-Related Proteinuria: Diagnostic Delay from Limited Biopsy

Session Information

• Glomerular Diseases: Genetics to Therapeutics
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Salih, Noman, TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Noman Salih, MD

• Khan, Asmad, TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Asmad Khan, MD

• Ullah, Izhar, TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Izhar Ullah, MD

• Shah, Neal B., TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Neal B. Shah, MD

• Hanif, Muhammad Owais, TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Muhammad Owais Hanif, MD

• Arif, Ali, TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Ali Arif, MD, MBBS, FASN

• Khan, Kazi S., TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Kazi S. Khan, MD

Introduction

Focal segmental glomerulosclerosis (FSGS) is a histologic pattern with diverse etiologies, including COL4A3-associated Alport spectrum disease (ASD). Diagnosis may be confounded by sampling limitation and anchoring bias in pregnancy-associated proteinuria.

Case Description

A 27-year-old woman developed proteinuria (3.5 g) at 38 weeks gestation, initially attributed to preeclampsia. Baseline creatinine was 1.1 mg/dL (eGFR 60’s), transiently rising to 2.5 mg/dL before recovery after delivery. Persistent postpartum proteinuria prompted kidney biopsy. Biopsy showed FSGS on light and electron microscopy; however, immunofluorescence was non-diagnostic due to absence of glomeruli in the sample, leading to a diagnosis of primary FSGS.
She was treated with corticosteroids, mycophenolate, and tacrolimus with partial improvement in proteinuria and albumin, but kidney function declined to CKD stage 3b despite RAAS blockade and SGLT2 inhibition.
At 3 years persistent proteinuria and worsening kidney functions prompted genetic testing which revealed a pathogenic COL4A3 variant. Repeat biopsy showed segmental loss of α5 staining in the glomerular basement membrane (BM) with preserved staining in Bowman’s capsule and distal tubular BM and intact α2 staining, consistent with autosomal ASD. Immunosuppression was discontinued.

Discussion

This case highlights a diagnostic cascade driven by pregnancy-related anchoring bias and limited initial biopsy, where FSGS represented a secondary pattern rather than primary disease. Delayed diagnosis led to prolonged, ineffective immunosuppression and progressive CKD.

COL4A3-associated ASD should be considered in young adults with presumed primary FSGS who demonstrate an atypical response to therapy, particularly when biopsy findings are limited. Early genetic testing and repeat biopsy may help prevent misdiagnosis and unnecessary immunosuppression.