A 28-year-old male presents to the emergency department with sudden onset hematuria and flank pain. He reports a sore throat 2 weeks ago that resolved spontaneously. On examination, blood pressure is 152/98 mmHg, and there is mild bilateral costovertebral angle tenderness. Urinalysis shows 3+ blood, RBC casts, and dysmorphic RBCs. Serum creatinine is 1.8 mg/dL (baseline 0.9 mg/dL). Complement levels (C3 and C4) are normal. Throat culture is negative. What is the most likely diagnosis?

Explanation

## Clinical Presentation & Diagnosis This patient presents with the classic features of **IgA Nephropathy (Berger's Disease)**: - Gross hematuria occurring **synpharyngitically** (within 1–5 days of upper respiratory infection) - Acute nephritic syndrome (hematuria, RBC casts, dysmorphic RBCs, hypertension, acute kidney injury) - **Normal complement levels (C3 and C4)** — a critical distinguishing feature ### Key Diagnostic Features **High-Yield:** IgA nephropathy is the most common primary glomerulonephritis worldwide. It classically presents with **synpharyngitic hematuria** — hematuria occurring simultaneously with or within days of an upper respiratory infection, in contrast to the 1–3 week latent period seen in PSGN. **Key Point:** The **normal C3 and C4** in this patient strongly argue against PSGN (which characteristically shows **low C3** with normal C4 during the acute phase) and against MPGN type I (which shows low C3 and low C4). Normal complement levels are characteristic of IgA nephropathy. **Clinical Pearl:** The 2-week interval described here is ambiguous, but the **normal complement** is the decisive clue. In PSGN, C3 is depressed at presentation in >90% of cases and normalizes within 6–8 weeks. A normal C3 at presentation effectively excludes PSGN. ### Distinguishing IgA Nephropathy from PSGN | Feature | IgA Nephropathy | PSGN | | --- | --- | --- | | **Onset after infection** | Synpharyngitic (0–5 days) | 1–3 weeks (pharyngitis); 3–6 weeks (skin) | | **C3 level** | **Normal** | **Low** (in >90% at presentation) | | **C4 level** | Normal | Normal | | **Age** | Young adults (20s–30s) | Children (5–15 years) | | **Recurrence** | Common | Rare | | **Throat culture** | Negative | May be positive for GAS | | **Serum IgA** | Elevated in ~50% | Normal | | **Immunofluorescence** | Mesangial IgA deposits | Granular C3 ± IgG (subepithelial) | ### Pathophysiology of IgA Nephropathy 1. Aberrantly glycosylated IgA1 (galactose-deficient) is produced in response to mucosal infections 2. Anti-glycan IgG/IgA antibodies form immune complexes with aberrant IgA1 3. Immune complexes deposit in the **mesangium** 4. Complement activation via the **alternative and lectin pathways** (not classical) → mesangial proliferation and injury ### Why Other Options Are Incorrect - **Lupus nephritis (A):** Requires systemic features (rash, arthritis, serositis), positive ANA/anti-dsDNA, and typically shows low C3 AND low C4 - **MPGN type I (B):** Shows persistently low C3 and low C4; presents insidiously without a clear post-infectious trigger - **PSGN (D):** Requires low C3 at presentation; the normal complement in this patient effectively excludes this diagnosis per Harrison's Principles of Internal Medicine ### Management of IgA Nephropathy - Optimize blood pressure control (target <125/75 mmHg with proteinuria) - ACE inhibitors or ARBs (first-line for proteinuria reduction) - Fish oil (omega-3 fatty acids) for persistent proteinuria - Corticosteroids for progressive disease (proteinuria >1 g/day despite supportive care) - Tonsillectomy may reduce hematuria episodes in selected patients **Key Point:** Per *Harrison's Principles of Internal Medicine* (21st ed.) and *Robbins & Cotran Pathologic Basis of Disease* (10th ed.), IgA nephropathy is characterized by mesangial IgA deposits, normal complement, and synpharyngitic hematuria — all consistent with this clinical vignette.