What is the role of Clopidogrel (Plavix) in Focal Segmental Glomerulosclerosis (FSGS)?

From the Guidelines

Clopidogrel is not recommended as a standard treatment for Focal Segmental Glomerulosclerosis (FSGS) due to the lack of clinical evidence supporting its efficacy in this context. The primary treatments for FSGS, as outlined in the KDIGO 2021 guideline for the management of glomerular diseases 1, typically include high-dose glucocorticoids, calcineurin inhibitors, and other immunosuppressive agents. Clopidogrel, being an antiplatelet medication, does not directly address the underlying pathophysiology of FSGS, which involves podocyte injury and immune dysregulation.

Treatment Options for FSGS

• High-dose glucocorticoids, such as prednisone, are recommended as first-line therapy for FSGS, with a starting dose of 1 mg/kg/day for 4-16 weeks 1.
• Calcineurin inhibitors, such as cyclosporine or tacrolimus, are recommended for glucocorticoid-resistant or intolerant patients, with a starting dose of 3-5 mg/kg/day or 0.05-0.1 mg/kg/day, respectively 1.
• Other immunosuppressive agents, such as mycophenolate mofetil or rituximab, may be considered in certain cases, although there is limited evidence to support their use in FSGS.

Rationale for Not Recommending Clopidogrel

While there has been some theoretical interest in antiplatelet agents for certain kidney diseases due to their potential to reduce intraglomerular thrombosis and inflammation, there is insufficient clinical evidence supporting clopidogrel's efficacy specifically for FSGS. The KDIGO 2021 guideline does not mention clopidogrel as a recommended treatment for FSGS, and the available evidence does not suggest a clear benefit of clopidogrel in reducing proteinuria or preserving kidney function in patients with FSGS 1.

Clinical Implications

Management of FSGS should focus on proven therapies that target proteinuria reduction, preservation of kidney function, and addressing the underlying cause of FSGS when identifiable. Clinicians should prioritize the use of established treatments, such as glucocorticoids and calcineurin inhibitors, and consider referral to an expert center for patients with resistant or complex disease.

From the Research

Role of Clopidogrel in FSGS

• Clopidogrel, an anti-platelet drug, has been identified as a potential therapeutic option for Focal Segmental Glomerulosclerosis (FSGS) through computational drug repositioning 2.
• The study found that clopidogrel improved key FSGS outcome parameters, including reducing urinary albumin to creatinine ratio and weight loss, and ameliorating histopathological damage in an adriamycin FSGS mouse model 2.
• Clopidogrel's favorable safety profile and efficacy in the mouse model recommend it as an attractive drug repositioning candidate for clinical trial in FSGS 2.

Current Treatment of FSGS

• Current treatment of FSGS is limited to systemic corticosteroids or calcineurin inhibition, along with inhibitors of the renin-angiotensin-aldosterone system 2.
• Other treatment options include cyclosporine A, cytotoxic therapy, and plasmapheresis or protein adsorption for renal transplant patients with recurrent FSGS 3.
• However, these treatments have limited efficacy and are often associated with significant side effects.

Pathogenesis and Classification of FSGS

• FSGS is a heterogeneous entity with diverse clinicopathological entities and different mechanisms of injury, with the podocyte as the principal target of lesion 4, 5, 6.
• The classification of FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and genetic testing 6.
• Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight 6.