Kidney Week

Abstract: FR-PO0703

Refractory Seropositive but Biopsy-Negative Anti-Nephrin Antibody-Associated Podocytopathy: A Case Report

Session Information

• Glomerular Diseases: Membranous Nephropathy, FSGS, and Podocytopathies
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Aoyagi, Izumi, Kameda Medical Center, Kamogawa, Chiba Prefecture, Japan

Izumi Aoyagi, MD

• Shirai, Yoko, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Yoko Shirai, MD, PhD

• Shimogawa, Maiko, Kameda Medical Center, Kamogawa, Chiba Prefecture, Japan

Maiko Shimogawa

• Tanaka, Rina, Kameda Medical Center, Kamogawa, Chiba Prefecture, Japan

Rina Tanaka, MD

• Ohara, Mamiko, Kameda Medical Center, Kamogawa, Chiba Prefecture, Japan

Mamiko Ohara, MD, PhD, FASN

• Miura, Kenichiro, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Kenichiro Miura, MD, PhD

• Hattori, Motoshi, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Motoshi Hattori, MD, PhD

• Suzuki, Tomo, Kameda Medical Center, Kamogawa, Chiba Prefecture, Japan

Tomo Suzuki, MD, PhD

Introduction

Some patients with minimal change disease (MCD) exhibit resistance to standard therapies; however, reports examining the role of anti-nephrin antibodies in such cases are limited. We describe a case of treatment-resistant nephrotic syndrome initially diagnosed as MCD, and characterized by positive serum anti-nephrin antibodies and negative anti-nephrin staining in kidney tissue. Additionally, a second biopsy revealed progression from MCD to focal segmental glomerulosclerosis (FSGS).

Case Description

A 60-year-old man with a history of postoperative oropharyngeal cancer, gout, and eight years of hypertension developed generalized edema within one month. Laboratory results showed a urine protein-creatinine ratio of 7.0 g/gCr, serum albumin of 2.7 g/dL, and LDL cholesterol of 143 mg/dL, leading to a diagnosis of nephrotic syndrome.
Kidney biopsy revealed 20 glomeruli on light microscopy, with no segmental lesions, and findings consistent with minimal change disease. Electron microscopy demonstrated diffuse podocyte foot process effacement without electron-dense deposits. Based on these findings, MCD was diagnosed.
High-dose corticosteroid therapy (prednisolone 40 mg) and rituximab (500 mg, three times) were administered, but failed to induce clinical remission. Subsequently, five sessions of LDL apheresis were performed, followed by combination therapy with cyclosporine and mycophenolate mofetil. Urinary protein excretion gradually decreased and serum albumin levels improved; however, complete remission was not achieved nine months after treatment initiation. A second kidney biopsy revealed FSGS lesions.
Additional analyses showed that the pretreatment serum anti-nephrin antibody level was 113 U/mL (cutoff value 231 U/mL), while the serum anti-nephrin antibody-to-IgG ratio was elevated at 38.7 U/mg (cutoff value 30 U/mg). In contrast, immunostaining for both nephrin and IgG in kidney tissue was negative.

Discussion

In membranous nephropathy, discordance between positive serum autoantibodies and negative renal tissue staining has been associated with severe disease. However, similar observations are rarely reported in podocytopathy. This refractory case, characterized by seropositive but biopsy-negative anti-nephrin antibody, which also demonstrated FSGS lesions on repeat biopsy, may suggest a potentially severe disease phenotype in podocytopathy.