Kidney Week

Abstract: TH-OR094

Pretreatment Antinephrin Antibody Titers Stratify Nephrotic Syndrome in Pediatric Patients and Predict Steroid Response, Independent of Genetic Risk Alleles

Session Information

• Shaping Pediatric Kidney Disease: Developmental Insights, Stem Cell Systems, Novel Biomarkers, and More
  October 22, 2026 | Location: Room 603, Convention Center
  Abstract Time: 05:00 PM - 05:10 PM

Category: Pediatric Nephrology

• 1800 Pediatric Nephrology

Authors

• Horinouchi, Tomoko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Tomoko Horinouchi, MD, PhD

• Muto, Masaya, Central Research Laboratories, Sysmex Corporation, Kobe, Japan

Masaya Muto, MS

• Nagano, China, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

China Nagano, MD, PhD

• Ozeki, Takaya, Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Takaya Ozeki, MD, PhD

• Inoki, Yuta, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Yuta Inoki, MD, MEd

• Ichikawa, Yuta, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Yuta Ichikawa

• Yamamoto, Eri Morita, Central Research Laboratories, Sysmex Corporation, Kobe, Japan

Eri Morita Yamamoto

• Kamei, Koichi, Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan

Koichi Kamei, MD, PhD

• Hamada, Riku, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan

Riku Hamada, MD

• Isaka, Yoshitaka, Department of Nephrology, The University of Osaka, Osaka, Japan

Yoshitaka Isaka, MD, PhD

• Maruyama, Shoichi, Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Shoichi Maruyama, MD, PhD

• Ishikura, Kenji, Department of Pediatrics, Kitasato University School of Medicine, Tokyo, Japan

Kenji Ishikura, MD, PhD

• Harada, Amane, Central Research Laboratories, Sysmex Corporation, Kobe, Japan

Amane Harada, PhD

• Nozu, Kandai, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Kandai Nozu, MD, PhD

• Iijima, Kazumoto, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Kazumoto Iijima, MD, PhD

Background

Pediatric nephrotic syndrome (NS) may progress to steroid–sensitive NS (SSNS) or steroid–resistant NS (SRNS) or be diagnosed as other nephropathy during the disease course. Nephrin is a proposed autoimmune target, but the clinical significance of anti–nephrin antibodies at NS onset and their association with genetic risk remain unclear.

Methods

We developed a highly sensitive automated immunoassay for circulating anti–nephrin antibodies using a recombinant human nephrin extracellular domain with three substituted cysteine residues to enhance sensitivity. Bound antibodies were detected by chemiluminescence on an automated platform (HISCL–5000). Using this assay, we prospectively evaluated 103 Japanese children with newly diagnosed NS and analyzed associations between anti–nephrin antibody titers, clinical phenotype, time to remission, and HLA (rs3129888) and NPHS1 (rs2285450) risk alleles. Serum or plasma samples were obtained before treatment and after remission.

Results

At disease onset, 92 of 103 patients (89.3%) were positive for anti–nephrin antibodies, with levels decreasing during remission in all but one case. All patients who developed SSNS (n=83) were antibody–positive, whereas all those diagnosed with IgA nephropathy (n=4) were antibody–negative. Among patients progressing to SRNS (n=16), antibody–negative cases (n=7) and high–titer cases (>7,783 SU/mL, n=9) were identified; this cutoff discriminated SRNS from SSNS with 100% sensitivity and 92.8% specificity. Patients with either high titers or antibody negativity had a significantly increased risk of progressing to SRNS or non–idiopathic NS, compared with those with intermediate titers (P<0.0001). In SSNS, pretreatment antibody titers correlated positively with time to remission (Spearman's ρ=0.264, p=0.0166), indicating delayed remission in patients with higher titers. Baseline anti–nephrin antibody levels were not associated with HLA or NPHS1 risk alleles.

Conclusion

Anti–nephrin antibodies are highly prevalent at disease onset in pediatric SSNS and decrease with treatment. Pretreatment antibody titers provide strong diagnostic and prognostic value for disease classification and clinical course, independent of genetic risk alleles, supporting their role as a clinically actionable biomarker for personalized management of pediatric NS.

Funding

• Government Support – Non-U.S.