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Background <p>C3 glomerulonephritis (C3GN) is a rare renal disorder caused by dysregulation of the alternative complement pathway, resulting in abnormal C3 activation and deposition. Current treatments, including immunosuppressants such as mycophenolate mofetil and glucocorticoids, sometimes yield limited efficacy. Complement inhibitors are under investigation but remain unapproved for clinical use. Low-density lipoprotein (LDL) apheresis, originally developed for severe hyperlipidemia, has shown therapeutic potential in nephrotic syndromes through mechanisms beyond lipid reduction. Emerging evidence suggests that LDL apheresis may rapidly reduce proteinuria; however, its precise role in C3GN remains unclear.</p> Case presentation <p>A 10-year-old Japanese female presented with persistent hematuria and proteinuria identified during school urine screening. Despite normal kidney function and serum albumin levels, C3-dominant hypocomplementemia prompted renal biopsy. Histopathological examination revealed diffuse endocapillary and mesangial hypercellularity, with significant C3 deposition and minimal C1q presence. On the basis of histological findings and clinical course, the patient was diagnosed with C3GN. Genetic testing identified a rare complement B factor mutation linked to complement pathway dysregulation.</p> <p>The patient’s condition progressed to nephrotic syndrome, refractory to treatments, including high-dose corticosteroids, mycophenolate mofetil, and statins. Hypocomplementemia persisted throughout the disease course. At age 16&#xa0;years, LDL apheresis was initiated using the Liposorber<sup>®</sup> LA-15 system, achieving a 52.6% proteinuria reduction the day after therapy, suggesting mechanisms independent of lipid-lowering. Adjunctive therapies, including methylprednisolone pulses and intensified statin treatment, achieved partial remission for 6&#xa0;months; however, proteinuria and hypoalbuminemia recurred 9&#xa0;months post-therapy.</p> Conclusions <p>This is the first case report that highlights an earlier therapeutic response, underscoring the potential of LDL apheresis in refractory C3GN. The immediate proteinuria reduction observed post-apheresis suggests a possible mechanism involving pathogenic humoral factor removal beyond lipid-lowering effects. This outcome contrasts with prior reports of delayed responses, emphasizing the need for further research on LDL apheresis in C3GN management. Future studies should explore the broader applicability and mechanisms of LDL apheresis in C3GN and other renal disorders.</p>

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Low-density lipoprotein apheresis shows a rapid response to proteinuria due to C3 glomerulonephritis: a case report and literature review

  • 期刊论文

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  • 发表日期：

    2025年7月1日

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  • Hideki Matsumura,
  • Yuko Fujii,
  • Tomoko Tanaka,
  • Maki Kagitani,
  • Akira Ashida

摘要

Background

C3 glomerulonephritis (C3GN) is a rare renal disorder caused by dysregulation of the alternative complement pathway, resulting in abnormal C3 activation and deposition. Current treatments, including immunosuppressants such as mycophenolate mofetil and glucocorticoids, sometimes yield limited efficacy. Complement inhibitors are under investigation but remain unapproved for clinical use. Low-density lipoprotein (LDL) apheresis, originally developed for severe hyperlipidemia, has shown therapeutic potential in nephrotic syndromes through mechanisms beyond lipid reduction. Emerging evidence suggests that LDL apheresis may rapidly reduce proteinuria; however, its precise role in C3GN remains unclear.

Case presentation

A 10-year-old Japanese female presented with persistent hematuria and proteinuria identified during school urine screening. Despite normal kidney function and serum albumin levels, C3-dominant hypocomplementemia prompted renal biopsy. Histopathological examination revealed diffuse endocapillary and mesangial hypercellularity, with significant C3 deposition and minimal C1q presence. On the basis of histological findings and clinical course, the patient was diagnosed with C3GN. Genetic testing identified a rare complement B factor mutation linked to complement pathway dysregulation.

The patient’s condition progressed to nephrotic syndrome, refractory to treatments, including high-dose corticosteroids, mycophenolate mofetil, and statins. Hypocomplementemia persisted throughout the disease course. At age 16 years, LDL apheresis was initiated using the Liposorber® LA-15 system, achieving a 52.6% proteinuria reduction the day after therapy, suggesting mechanisms independent of lipid-lowering. Adjunctive therapies, including methylprednisolone pulses and intensified statin treatment, achieved partial remission for 6 months; however, proteinuria and hypoalbuminemia recurred 9 months post-therapy.

Conclusions

This is the first case report that highlights an earlier therapeutic response, underscoring the potential of LDL apheresis in refractory C3GN. The immediate proteinuria reduction observed post-apheresis suggests a possible mechanism involving pathogenic humoral factor removal beyond lipid-lowering effects. This outcome contrasts with prior reports of delayed responses, emphasizing the need for further research on LDL apheresis in C3GN management. Future studies should explore the broader applicability and mechanisms of LDL apheresis in C3GN and other renal disorders.