Cyclosporine-Induced Remission in Pediatric focal segmental glomerulosclerosis with Anti-Nephrin Autoantibody Positivity

Background:
Anti-nephrin autoantibodies, targeting a key slit diaphragm protein, have recently been reported in subsets of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), correlating with proteinuria and disease activity. Nevertheless, their clinical implications remain incompletely understood, particularly in relation to immunosuppressive therapy. And it remains unclear whether calcineurin inhibitors such as cyclosporine (CsA) can influence autoantibody-mediated disease processes.

Case presentation:
A 10-year-old girl with no family history of kidney disease developed idiopathic nephrotic syndrome. Prednisolone (PSL, 2 mg/kg/day) for 3 weeks failed to induce remission, and she was referred to our hospital. At the time of transfer, she presented with generalized edema, heavy proteinuria (urine protein/creatinine ratio 7.6 g/gCr), hypoalbuminemia (total protein 4.25 g/dL, albumin 1.49 g/dL), and hypercholesterolemia (423 mg/dL), with preserved renal function. Proteinuria persisted despite continued PSL treatment for a total of four weeks, leading to the diagnosis of steroid-resistant nephrotic syndrome (SRNS). Renal biopsy on day 30 of PSL therapy showed FSGS, perihilar variant, with segmental hyalinosis and no immunoglobulin or complement deposition. High-dose cyclosporine (CsA; target trough 120–150 ng/mL) was added to PSL, inducing partial remission at 2 months and complete remission at 4 months, sustained thereafter.

Findings:
Renal biopsy tissue was positive for anti-nephrin autoantibodies, suggesting their involvement in the disease process. Serial serum titers were 96 U/mL at referral, 154 U/mL at CsA initiation, 295 U/mL at partial remission, 223 U/mL at complete remission, and 77 U/mL several months after sustained remission, with a cutoff value of 226 U/mL. Interestingly, antibody titers were relatively low during periods of heavy proteinuria, possibly reflecting intrarenal deposition, consumption, or urinary loss. They rose transiently during partial remission and subsequently declined below the cutoff in parallel with sustained remission. This course suggests that CsA may influence not only T-cell activity and podocyte stabilization but also humoral immunity and autoantibody production.

Conclusion:
We present a pediatric FSGS case in which renal tissue demonstrated positivity for anti-nephrin autoantibodies, implicating their involvement in the disease process, and cyclosporine was effective. Further accumulation and analysis of similar cases will be essential to clarify the clinical significance of anti-nephrin antibodies and to optimize treatment strategies.

This abstract is based on a case previously presented at the Kyushu Nephrology Meeting in 2025, with additional analyses and updated discussion. Re-submission of this work has been permitted by the meeting organizers.

Conflict of Interest statement:
The authors declare no conflicts of interest relevant to this work.

AI statement:
Artificial intelligence (AI)–assisted technology (ChatGPT, OpenAI) was used to refine the English language and improve the clarity of this abstract. All content was reviewed and approved by the authors, who take full responsibility for the work.