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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Mutations in the NPHS1 gene, encoding the slit diaphragm protein Nephrin, typically cause severe Congenital Nephrotic Syndrome (CNS) progressing rapidly to ESRD. However, certain missense variants, particularly when combined in a compound heterozygous state, are associated with later-onset, milder forms of Focal Segmental Glomerulosclerosis (FSGS). The c.2464G>A (p.(Val822Met)) is a Japanese population hotspot linked to indolent progression. However, a case demonstrating the actual clinical course extending into the fifth decade of life has not been reported previously. We report a patient with an exceptionally long, slow-progressing course of the NPHS1-related nephropathy.
A 57-year-old Japanese male presented with facial edema and increased proteinuria (UPCR 5.71 g/gCre). He was diagnosed with nephrotic syndrome (NS) at age 3. He was classified as steroid-resistant nephrotic syndrome (SRNS) after failing a one-year course of prednisolone (PSL) and was subsequently followed untreated for decades, maintaining proteinuria in annual urine tests. At age 42, he began moderate-dose PSL for co-existing autoimmune hepatitis (AIH), which did not resolve the proteinuria. At age 51, he presented with NS (s-Alb 2.9 g/dL, UPCR 3.56g/gCre), but kidney biopsy was non-diagnostic. A repeat biopsy at age 52, prompted by increased proteinuria, revealed segmental sclerosing lesions at the perihilar variant, in one out of 17 sampled glomeruli with diffuse foot process effacement, confirming FSGS.
Genetic analysis detected two previously reported missense variants in NPHS1: c.1135C>T (p.(Arg379Trp), Pathogenic) and c.2464G>A (p.(Val822Met), Pathogenic). The compound heterozygosity of these variants is considered causative for Genetic FSGS. The latter variant successfully traffics to the plasma membrane but restricts the lateral assembly dynamics of Nephrin, which allows for residual limited slit diaphragm function. Despite 54 years of disease evolution since childhood onset, his current renal function is maintained at eGFR 38.5 mL/min/1.73m², managed solely with supportive therapy (ACE inhibitor), confirming a highly indolent course.
This case represents the first documented clinical trajectory of NPHS1-related nephropathy extending into the patient's late 50s, providing the longest follow-up for this genotype. It definitively demonstrates that the p.(Val822Met) acts as a profound phenotypic modifier, delaying FSGS progression until late adulthood. This report emphasizes the critical role of genetic testing in diagnosing adult-onset or seemingly idiopathic SRNS and FSGS, providing crucial prognostic information and ensuring appropriate avoidance of unnecessary immunosuppressive agents.
This abstract was also presented at the 55th Eastern Regional Meeting of the Japanese Society of Nephrology, Yokohama, Japan.
