A 42-year-old woman with systemic lupus erythematosus presents with fever, malaise, and progressive dyspnea for 5 days. She reports dark-colored urine and decreased urine output. On examination, blood pressure is 148/92 mmHg, respiratory rate 24/min, and bilateral crackles are heard. Laboratory findings: serum creatinine 2.8 mg/dL (baseline 0.9 mg/dL), BUN 52 mg/dL, hemoglobin 8.2 g/dL, platelet count 45,000/μL, and LDH 680 U/L. Urinalysis shows 3+ proteinuria, dysmorphic RBCs, RBC casts, and WBC casts. Serum complement C3 is low. What is the most likely diagnosis?

Explanation

## Clinical Analysis **Key Point:** The constellation of dysmorphic RBCs, RBC casts, proteinuria, low complement C3, and systemic lupus erythematosus in a patient with acute renal failure is diagnostic of lupus nephritis with acute glomerulonephritis. ### Diagnostic Criteria for Lupus Nephritis | Feature | Finding | Significance | |---------|---------|---------------| | **Urinary RBC casts** | Present | Pathognomonic for glomerulonephritis | | **Dysmorphic RBCs** | Present | Indicates glomerular origin of hematuria | | **Proteinuria** | 3+ (nephrotic range likely) | Glomerular capillary injury | | **WBC casts** | Present | Active glomerular inflammation | | **Low C3** | Yes | Immune complex-mediated disease (SLE hallmark) | | **Hemolytic anemia** | Hgb 8.2 (low) | Microangiopathic hemolytic anemia (MAHA) component | | **Thrombocytopenia** | 45,000/μL | Part of SLE manifestation, also suggests TMA | | **Elevated LDH** | 680 U/L | Hemolysis marker | | **Systemic disease** | Fever, malaise, dyspnea | Multi-organ SLE involvement | **High-Yield:** RBC casts are the gold standard for diagnosing glomerulonephritis. They indicate that red blood cells have been trapped within a fibrin matrix in the glomerulus—this is intrinsic glomerular disease, not prerenal or tubular. ### Pathophysiology of Lupus Nephritis ```mermaid flowchart TD A[SLE: Loss of immune tolerance]:::outcome --> B[Autoantibody production<br/>anti-dsDNA, anti-nucleosome] B --> C[Immune complex formation] C --> D[Deposition in glomeruli] D --> E[Complement activation<br/>C3 consumption] E --> F[Glomerular inflammation] F --> G[Endocapillary proliferation] G --> H[RBC casts, proteinuria,<br/>dysmorphic RBCs]:::outcome H --> I[Acute glomerulonephritis<br/>with AKI]:::outcome ``` **Mnemonic: CASTS in Lupus Nephritis** — **C**irculating immune **C**omplexes, **A**utoantibodies (anti-dsDNA), **S**evere glomerular **S**welling, **T**ubular **T**hrombosis (in severe cases), **S**ubendothelial **S**pikes (electron microscopy finding). ### Why This Is NOT Thrombotic Microangiopathy (TMA)? **Clinical Pearl:** Although thrombocytopenia and hemolytic anemia are present (suggesting TMA), the presence of RBC casts and low C3 complement strongly favor lupus nephritis. TMA typically shows: - Schistocytes on blood smear (not mentioned; would be expected) - Normal or only mildly elevated creatinine initially (this patient has significant rise) - Absence of immune complex markers (C3 would be normal in typical TMA) - No dysmorphic RBCs or casts (mechanical hemolysis, not glomerular) **Key Point:** The combination of **RBC casts + low C3 + SLE diagnosis** is virtually pathognomonic for lupus nephritis, even if TMA features coexist. ### Classification of Lupus Nephritis (WHO/ISN-RPS) | Class | Histology | Clinical Features | |-------|-----------|-------------------| | I | Minimal mesangial | Asymptomatic hematuria/proteinuria | | II | Mesangial proliferation | Mild proteinuria, preserved function | | III | Focal proliferative | Active urinary sediment, moderate proteinuria | | IV | Diffuse proliferative | **Most common; worst prognosis** | | V | Membranous | Nephrotic syndrome | | VI | Advanced sclerotic | Chronic kidney disease | This patient's presentation (acute AKI, active sediment, low C3) is consistent with **Class III or IV** lupus nephritis. ### Management Approach 1. **Confirm diagnosis:** Renal biopsy (gold standard) 2. **Immunosuppression:** Induction therapy (corticosteroids + cyclophosphamide or mycophenolate mofetil) 3. **Supportive care:** ACE inhibitor/ARB, blood pressure control, fluid management 4. **Monitor:** Serum creatinine, proteinuria, complement levels, anti-dsDNA titers [cite:Harrison 21e Ch 319]