Kidney Week

Abstract: FR-PO0134

Steroid-Sensitive Genetic FSGS Associated with a CD2AP Variant Achieving Sustained Remission After Rituximab: A Sibling Case Series

Session Information

• Hereditary Glomerular and Tubulointerstitial Kidney Diseases
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Michael, Hany Tobia, Dubai Academic Health Corporation, Dubai, United Arab Emirates

Hany Tobia Michael, MD

• Hamadah, Abdurrahman M., Dubai Academic Health Corporation, Dubai, United Arab Emirates

Abdurrahman M. Hamadah, MD

• Alalawi, Fakhriya Juma Abdulla, Dubai Academic Health Corporation, Dubai, United Arab Emirates

Fakhriya Juma Abdulla Alalawi, MBBS, FASN

• Soliman, Malaz Noralla, Dubai Academic Health Corporation, Dubai, United Arab Emirates

Malaz Noralla Soliman, MD, MBBS

• Alhadari, Amna Khalifa, Dubai Academic Health Corporation, Dubai, United Arab Emirates

Amna Khalifa Alhadari, PhD

Introduction

Genetic focal segmental glomerulosclerosis (FSGS) is classically steroid resistant and poorly responsive to immunosuppression. Mutations affecting podocyte structural proteins disrupt slit diaphragm signaling and cytoskeletal integrity, leading to progressive disease. CD2-associated protein (CD2AP) is an essential adaptor protein regulating podocyte actin dynamics and filtration barrier stability. Steroid responsiveness and successful immunomodulatory therapy in genetic FSGS are rare. We describe two siblings with early-onset nephrotic syndrome carrying the same CD2AP variant who demonstrated steroid sensitivity and durable remission following rituximab therapy.

Case Description

A 23-year male-brother (onset age 3) and 30-year-old-sister (onset age 4), born to unaffected parents, developed frequently relapsing steroid-sensitive nephrotic syndrome. Both required prolonged calcineurin inhibitor (CNI) therapy for relapse prevention as steroid sparing measures, however continued to have intermittent relapses. Kidney biopsies demonstrated FSGS in the sister, and minimal change disease in the brother (question of unsampled FSGS) with diffuse podocyte foot process effacement (>80%). Genetic testing identified an identical heterozygous CD2AP variant (NM_012120.3:c.1594C>T; p.P532S) in both siblings. Relapses were marked by nephrotic-range proteinuria (6–8 g/g), hypoalbuminemia (2–2.5 g/dL), and edema while kidney function remained normal. Given the frequent relapses, it was decided to treat with Rituximab and each received a dose of 1 gram. Both attained complete remission which persists one year later, while maintained on low dose CNI which is being tapered.

Discussion

These cases highlight an atypical phenotype of genetic FSGS demonstrating steroid sensitivity and response to B-cell depletion. Partial CD2AP dysfunction may allow immune-mediated podocyte injury superimposed on genetic susceptibility, explaining therapeutic responsiveness. Although genetic FSGS is often considered non-immune, our observations suggest phenotypic heterogeneity and potential benefit of rituximab in selected patients. Sustained remission after single-dose rituximab with minimal ongoing immunosuppression challenges traditional therapeutic nihilism in genetic podocytopathies and supports incorporating genetic testing into management and counseling strategies.