# Clinical Cases: Glomerular Diseases

## Case 1: Minimal Change Disease

### Patient Presentation
**Demographics:** 5-year-old male

**Chief Complaint:** Facial and leg swelling for 1 week

**History of Present Illness:**
The patient's mother noticed swelling around his eyes 1 week ago, which has progressed to include his legs and abdomen. She reports he has been urinating less frequently and the urine appears "foamy." He had an upper respiratory infection 2 weeks ago that resolved. He has no history of similar episodes.

**Physical Examination:**
- Blood pressure: 100/60 mmHg (normal for age)
- Weight: 22 kg (up from 18 kg at last visit)
- General: Well-appearing but edematous
- HEENT: Periorbital edema
- Lungs: Clear
- Abdomen: Distended with shifting dullness (ascites)
- Extremities: 3+ pitting edema
- Skin: No rashes

### Workup and Results

**Laboratory Studies:**
- Creatinine: 0.4 mg/dL (normal)
- BUN: 12 mg/dL
- Albumin: 1.4 g/dL (low)
- Total cholesterol: 380 mg/dL (elevated)
- Urinalysis: 4+ protein, no blood, oval fat bodies
- Spot urine protein-to-creatinine ratio: 12 mg/mg (nephrotic range)
- C3 and C4: Normal

### Clinical Image

![Minimal Change Disease EM](case_01_image.jpg)

*Electron microscopy of minimal change disease demonstrating diffuse podocyte foot process effacement with otherwise normal glomerular basement membrane and no immune deposits.*

### Diagnosis
**Nephrotic Syndrome due to Minimal Change Disease**

Features supporting this diagnosis:
- Age (most common cause in children)
- Nephrotic-range proteinuria (>3.5 g/day equivalent)
- Hypoalbuminemia and hyperlipidemia
- Bland urine sediment (no hematuria)
- Normal complement levels

### Discussion
This case illustrates classic minimal change disease:

- **Most Common in Children**: The lecture notes MCD is the most common cause of nephrotic syndrome in children, accounting for 70-90% of cases under age 10.

- **Nephrotic Syndrome Definition**: Proteinuria >3.5 g/day (or equivalent ratio in children), hypoalbuminemia, hyperlipidemia, and edema. The lecture emphasizes that nephrotic-range proteinuria is the defining feature.

- **Pathophysiology**: T-cell dysfunction leads to circulating factors that damage podocytes. Light microscopy shows normal-appearing glomeruli; electron microscopy reveals diffuse foot process effacement.

- **Excellent Steroid Response**: The lecture states that 90% of patients achieve complete remission with corticosteroids, distinguishing MCD from other causes.

### Treatment Plan
1. **First-line Therapy:**
   - Prednisone 60 mg/m2/day (max 60 mg) for 4-6 weeks
   - Then alternate-day dosing and taper

2. **Supportive Care:**
   - Sodium restriction (<2 g/day)
   - Careful diuretic use for severe edema (furosemide with albumin)
   - No fluid restriction unless symptomatic

3. **Monitoring:**
   - Daily urine dipstick for protein
   - Weekly weights
   - Watch for complications (infection, thrombosis)

4. **Expected Response:**
   - Complete remission (negative protein) expected within 4 weeks
   - 70-80% relapse, often with intercurrent illness

### Teaching Points
1. Minimal change disease shows normal light microscopy but diffuse foot process effacement on EM
2. Children with first-episode nephrotic syndrome receive empiric steroids without biopsy
3. Nephrotic syndrome increases infection risk (immunoglobulin loss) and thrombosis risk

---

## Case 2: Membranous Nephropathy with Renal Vein Thrombosis

### Patient Presentation
**Demographics:** 52-year-old male

**Chief Complaint:** Leg swelling and sudden left flank pain

**History of Present Illness:**
The patient has had progressive lower extremity edema for 2 months. Today he developed sudden onset severe left flank pain radiating to the groin. He also notes foamy urine and a 10-pound weight gain. He has no history of kidney disease. He takes no medications and has no known malignancy.

**Physical Examination:**
- Blood pressure: 138/88 mmHg
- Heart rate: 102 bpm
- General: Uncomfortable, moderate distress
- Lungs: Clear
- Abdomen: Left-sided tenderness, no masses
- Extremities: 3+ bilateral pitting edema
- Left flank: Tenderness to palpation

### Workup and Results

**Laboratory Studies:**
- Creatinine: 1.6 mg/dL
- Albumin: 1.8 g/dL
- Total cholesterol: 420 mg/dL
- 24-hour urine protein: 9.2 g
- Urinalysis: 4+ protein, trace blood, oval fat bodies
- C3 and C4: Normal
- **Anti-PLA2R antibody: Positive (185 RU/mL)**
- ANA, hepatitis serologies: Negative

**CT Abdomen with Contrast:**
- Left renal vein thrombosis with extension into IVC
- Enlarged left kidney

**Renal Biopsy:**
- Light microscopy: Thickened capillary walls
- Immunofluorescence: Granular IgG and C3 along GBM
- Electron microscopy: Subepithelial deposits with spike and dome pattern

### Clinical Image

![Membranous Nephropathy](case_01_image.jpg)

*Renal biopsy demonstrating membranous nephropathy with characteristic "spike and dome" pattern on electron microscopy, showing subepithelial electron-dense deposits with intervening basement membrane projections.*

### Diagnosis
**Primary Membranous Nephropathy with Renal Vein Thrombosis**

- Anti-PLA2R positive (present in ~70% of primary MN)
- Nephrotic syndrome with heavy proteinuria
- Classic thrombotic complication

### Discussion
This case demonstrates membranous nephropathy and its complications:

- **Anti-PLA2R Antibodies**: The lecture describes how anti-PLA2R antibodies are found in approximately 70% of primary membranous nephropathy cases. A positive test can obviate biopsy in typical presentations.

- **Spike and Dome Pattern**: Characteristic EM finding as subepithelial deposits form and GBM projects around them. Immunofluorescence shows granular IgG staining.

- **Thromboembolism Risk**: The lecture emphasizes that membranous nephropathy carries particularly high thrombosis risk, especially renal vein thrombosis. This is due to urinary loss of anticoagulant proteins (antithrombin III) and increased hepatic synthesis of procoagulant factors.

- **Secondary Causes**: Always exclude malignancy (especially in older patients), hepatitis B, lupus, and medications (NSAIDs, gold).

### Treatment Plan
1. **Immediate Anticoagulation:**
   - Heparin transitioning to warfarin
   - Continue until nephrotic syndrome resolves
   - Prophylactic anticoagulation if albumin <2.5 g/dL

2. **RAAS Blockade:**
   - ACE inhibitor for proteinuria reduction

3. **Immunosuppression (for high-risk features):**
   - Rituximab (increasingly first-line)
   - OR cyclophosphamide plus corticosteroids
   - Monitor anti-PLA2R levels (correlate with disease activity)

4. **Cancer Screening:**
   - Age-appropriate malignancy workup
   - CT chest/abdomen/pelvis
   - Colonoscopy if indicated

### Teaching Points
1. Anti-PLA2R antibodies are highly specific for primary membranous nephropathy
2. Membranous nephropathy has the highest thrombosis risk among glomerular diseases
3. Albumin <2.5 g/dL warrants consideration of prophylactic anticoagulation
4. Always exclude secondary causes including malignancy

---

## Case 3: ANCA-Associated Glomerulonephritis

### Patient Presentation
**Demographics:** 68-year-old female

**Chief Complaint:** Blood in urine, fatigue, and shortness of breath for 2 weeks

**History of Present Illness:**
The patient noticed cola-colored urine 2 weeks ago along with progressive fatigue and dyspnea on exertion. She has had low-grade fevers, joint pains, and a 5-pound weight loss. She also reports a several-month history of recurrent sinusitis and epistaxis. No recent infections or medication changes.

**Physical Examination:**
- Blood pressure: 162/96 mmHg
- Heart rate: 88 bpm
- Temperature: 37.8C
- General: Ill-appearing
- HEENT: Nasal crusting, saddle nose deformity
- Lungs: Bibasilar crackles
- Skin: Palpable purpura on lower extremities
- Extremities: 1+ edema

### Workup and Results

**Laboratory Studies:**
- Creatinine: 4.8 mg/dL (baseline 0.9 three months ago)
- BUN: 68 mg/dL
- Hemoglobin: 9.2 g/dL
- Urinalysis: 3+ blood, 2+ protein, RBC casts, dysmorphic RBCs
- 24-hour urine protein: 2.1 g
- **c-ANCA (PR3): Strongly positive**
- p-ANCA (MPO): Negative
- C3 and C4: Normal
- Anti-GBM antibody: Negative

**Chest X-ray:**
- Bilateral pulmonary infiltrates concerning for hemorrhage

**Renal Biopsy:**
- Light microscopy: Crescentic glomerulonephritis (>50% crescents)
- Immunofluorescence: Pauci-immune (minimal to no staining)
- Electron microscopy: No immune deposits

### Clinical Image

![Crescentic GN](case_01_image.jpg)

*Renal biopsy demonstrating crescentic glomerulonephritis with cellular crescent formation (arrow) compressing the glomerular tuft. The pauci-immune pattern on immunofluorescence is characteristic of ANCA-associated vasculitis.*

### Diagnosis
**Granulomatosis with Polyangiitis (GPA) with Rapidly Progressive Glomerulonephritis**

- c-ANCA/PR3 positive (associated with GPA)
- Pulmonary-renal syndrome
- Upper respiratory involvement (sinusitis, saddle nose)
- Pauci-immune crescentic GN

### Discussion
This case illustrates ANCA-associated vasculitis:

- **RPGN Type III**: The lecture classifies RPGN by immunofluorescence pattern. Type III is pauci-immune (negative or minimal staining) and ANCA-associated. Types I (linear, anti-GBM) and II (granular, immune complex) have different mechanisms.

- **c-ANCA and PR3**: The lecture notes that c-ANCA targeting proteinase-3 (PR3) is most associated with granulomatosis with polyangiitis (formerly Wegener's). p-ANCA/MPO is associated with microscopic polyangiitis.

- **Crescent Formation**: Crescents form when inflammatory cells breach Bowman's capsule. More than 50% crescents indicates severe disease requiring urgent treatment.

- **Pulmonary-Renal Syndrome**: Concurrent lung and kidney involvement should prompt consideration of anti-GBM disease and ANCA vasculitis.

### Treatment Plan
1. **Induction Therapy:**
   - Pulse methylprednisolone (500-1000 mg IV daily x 3 days)
   - Rituximab OR cyclophosphamide
   - Consider plasma exchange for severe disease (creatinine >5.7 or pulmonary hemorrhage)

2. **Maintenance Therapy:**
   - Rituximab OR azathioprine
   - Low-dose prednisone taper

3. **Supportive Care:**
   - PCP prophylaxis (TMP-SMX)
   - Blood pressure control
   - May require temporary dialysis

4. **Monitoring:**
   - ANCA titers (rising may predict relapse)
   - Renal function
   - Watch for treatment-related infections

### Teaching Points
1. RPGN requires urgent diagnosis and treatment to preserve renal function
2. c-ANCA/PR3 is associated with GPA; p-ANCA/MPO with microscopic polyangiitis
3. Pauci-immune pattern on IF indicates ANCA-associated vasculitis
4. The classic triad of GPA involves upper respiratory, lower respiratory, and kidney

---

## Image Reference

For visual reference of glomerular disease concepts, see:
- Radiopaedia: [Glomerulonephritis](https://radiopaedia.org/articles/glomerulonephritis) - Overview and imaging
- Wikimedia Commons: [Kidney biopsy histology](https://commons.wikimedia.org/wiki/Category:Kidney_histopathology) - Pathologic findings
- Radiopaedia: [Crescentic glomerulonephritis](https://radiopaedia.org/articles/crescentic-glomerulonephritis) - Histologic features

---

## Learning Points

1. **Nephrotic vs Nephritic**: Nephrotic features heavy proteinuria, hypoalbuminemia, edema; nephritic features hematuria, RBC casts, hypertension, mild proteinuria

2. **MCD Responds to Steroids**: 90% of minimal change disease achieves complete remission with corticosteroids

3. **Anti-PLA2R for Membranous**: 70% of primary membranous nephropathy is anti-PLA2R positive

4. **Thrombosis in Nephrotic**: Membranous nephropathy has highest thrombosis risk; anticoagulate if albumin <2.5 g/dL

5. **ANCA Patterns**: c-ANCA/PR3 = GPA; p-ANCA/MPO = MPA; both cause pauci-immune crescentic GN