SUCCESSFUL TREATMENT OF IMMUNOSUPPRESSIVE THERAPY AND LDL-APHERESIS FOR NEPHROTIC SYNDROME CAUSED BY FIBRONECTIN GLOMERULOPATHY DIAGNOSED BY IMMUNOSTAINING AND GENETIC ANALYSIS

Fibronectin glomerulopathy (FNG) is an autosomal dominant hereditary kidney disease caused by pathogenic variants in the FN1 gene, which encodes plasma fibronectin. Mutant fibronectin abnormally deposits within the glomerular mesangium and subendothelial regions, leading to progressive glomerular injury. FNG is typically diagnosed in young adulthood. Most patients present with asymptomatic proteinuria or chronic glomerulonephritis, while nephrotic syndrome occurs in approximately 30% of reported cases. FNG is considered a non-immune-mediated condition, and no established treatment exists beyond supportive care; the efficacy of immunosuppressive therapy remains unclear. We report a case of FNG with nephrotic syndrome that achieved complete remission following immunosuppressive therapy and LDL-apheresis (LDL-A).

A 25-year-old man was referred to our hospital due to acute-onset edema. Laboratory tests revealed severe hypoalbuminemia (serum albumin 1.3 g/dL), massive proteinuria (urinary protein-to-creatinine ratio 8.7 g/gCr), and hyperlipidemia (LDL-cholesterol 308 mg/dL), consistent with nephrotic syndrome. Treatment was initiated on the day of admission, starting with intravenous methylprednisolone (1000 mg/day for three days), followed by oral prednisolone. Kidney biopsy revealed, on light microscopy, remarkable mesangial cell and matrix proliferation, along with subendothelial deposits that were negative for silver staining. Immunofluorescence revealed positivity for IgA, IgM, C3, and C1q, while staining for galactose-deficient IgA1 was negative. Electron microscopy demonstrated abundant subendothelial electron-dense deposits without organized structures. Immunohistochemistry showed IST4 positivity and IST9 negativity.　
We identified a previously reported heterozygous splice-site variant (c.5888-2A>G) in intron 36 of the FN1 gene, confirming the diagnosis of FNG. Cyclosporine was introduced as adjunctive therapy, and corticosteroids were gradually tapered. Due to persistent partial remission, LDL-A was performed at three months, resulting in a mild improvement in serum albumin levels. At 15 months, the patient experienced a relapse with declining serum albumin levels and recurrent edema. Prednisolone was reinitiated, and complete remission was achieved with corticosteroid monotherapy. Complete remission was achieved after 29 months, allowing discontinuation of immunosuppressive therapy. The patient has since maintained long-term remission.

Although FNG is not considered to involve an immunologic mechanism, several reports have described cases without coexisting autoimmune disease that responded favorably to corticosteroids or combined immunosuppressive therapy, such as mycophenolate mofetil. In our case, the clinical course also suggested a beneficial effect of immunosuppressive therapy and LDL-A.
LDL-A has been reported to exert renoprotective effects in patients with nephrotic syndrome by removing LDL cholesterol. However, its efficacy in FNG remains unclear. In our case, the patient initially presented with refractory nephrotic syndrome and underwent LDL-A, which led to a mild improvement in serum albumin levels.

We report a rare case of FNG presenting with nephrotic syndrome that achieved remission through a combination of immunosuppressive therapy and LDL-A. Further accumulation of clinical evidence is needed to clarify the therapeutic efficacy and long-term outcomes of LDL-A and immunosuppressive treatment in FNG.