## Clinical Context This patient presents with nephrotic syndrome in the absence of systemic disease (seronegative, normal complements, no clinical features of lupus or vasculitis). The clinical picture is consistent with primary glomerulonephritis, most likely minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). ## Why Kidney Biopsy Is Indicated **Key Point:** In seronegative nephrotic syndrome with normal renal function and no systemic disease, kidney biopsy is essential to differentiate between MCD (steroid-responsive, excellent prognosis) and FSGS (steroid-resistant, progressive). **High-Yield:** The histological diagnosis determines: - Treatment intensity (MCD responds to steroids alone; FSGS often requires additional agents) - Prognosis and counseling - Risk of progression and need for immunosuppression ## Management Algorithm ```mermaid flowchart TD A[Nephrotic syndrome + seronegative + normal complements]:::outcome --> B{Kidney biopsy done?}:::decision B -->|No| C[Perform kidney biopsy]:::action B -->|Yes| D{Histology?}:::decision D -->|MCD| E[Corticosteroids first-line]:::action D -->|FSGS| F[Steroids + consider second-line agents]:::action D -->|Other| G[Tailored immunosuppression]:::action ``` **Clinical Pearl:** Empirical steroid therapy without biopsy in seronegative nephrotic syndrome risks: - Unnecessary steroid exposure in FSGS (which is often steroid-resistant) - Delayed diagnosis of other glomerulonephritides - Inability to counsel on prognosis ## Rationale for Correct Answer **Key Point:** Biopsy-first approach in seronegative nephrotic syndrome is the standard of care because histology guides intensity and choice of immunosuppression. MCD (most common in this demographic) has >90% response to steroids; FSGS requires additional agents from the outset. [cite:Harrison 21e Ch 279] 
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