A 28-year-old man from rural India presents with sudden onset hematuria and mild flank pain for 3 days. He reports a sore throat 2 weeks prior that resolved spontaneously. On examination, blood pressure is 148/92 mmHg (previously normal). Urinalysis shows 3+ blood, RBC casts, and mild proteinuria (0.8 g/day). Serum creatinine is 1.2 mg/dL (baseline 0.9 mg/dL). Complement C3 levels are normal. Throat culture is negative. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: IgA Nephropathy (Berger's Disease) ### Key Clinical Features **Key Point:** IgA nephropathy is the most common primary glomerulonephritis worldwide and classically presents with episodic gross hematuria occurring concurrently with or shortly after an upper respiratory infection, with **normal complement levels**. This patient's presentation is classic for IgA nephropathy: 1. **Synpharyngitic hematuria** — hematuria occurring within days of a sore throat (concurrent or 1–5 days after URI, NOT 2–3 weeks later) 2. **Gross hematuria with RBC casts** — indicating glomerular origin 3. **Normal C3 complement** — a hallmark distinguishing IgA nephropathy from PSGN 4. **Mild proteinuria** (<1 g/day) — typical of IgA nephropathy 5. **Mild hypertension** — common at presentation ### Distinguishing Features: IgA Nephropathy vs. PSGN | Feature | IgA Nephropathy | Post-Streptococcal GN | MPGN | Alport Syndrome | |---------|-----------------|----------------------|------|-----------------| | **Latency after infection** | Concurrent or 1–5 days | 7–14 days (pharyngitis) | Variable | None (hereditary) | | **C3 complement** | **Normal** | ↓ in 50–80% of cases | ↓ (especially type II) | Normal | | **Proteinuria** | Mild to moderate | Mild (<1 g/day) | Heavy (>3 g/day) | Progressive | | **Hematuria pattern** | Episodic, gross with URI | Gross initially | Persistent microscopic | Progressive | | **Age/demographics** | Young adults, M>F | Children/young adults | Any age | Hereditary, family Hx | | **Prognosis** | Variable (25–30% → ESRD) | Excellent (>95% recovery) | Guarded | Poor (ESRD by 30s) | ### Why IgA Nephropathy is the Correct Diagnosis 1. **Normal C3:** This is the single most discriminating clue. PSGN causes hypocomplementemia (low C3) in 50–80% of active cases. A normal C3 strongly argues against PSGN and favors IgA nephropathy. 2. **Temporal relationship:** The hematuria began 3 days after a sore throat — this is "synpharyngitic" hematuria, characteristic of IgA nephropathy. PSGN has a latency of 7–14 days (pharyngitis) or 3–6 weeks (skin infection). 3. **Negative throat culture:** Consistent with a viral URI triggering IgA nephropathy, not necessarily streptococcal infection. 4. **RBC casts + mild proteinuria:** Classic nephritic pattern seen in IgA nephropathy. 5. **Young adult male:** IgA nephropathy has a male predominance and peaks in the 2nd–3rd decade. **Clinical Pearl:** The key teaching point is the **latency period** and **complement status**. IgA nephropathy = synpharyngitic (concurrent) + normal C3. PSGN = post-pharyngitic (7–14 day lag) + low C3. Alport syndrome requires a family history of renal disease and sensorineural hearing loss, neither of which is present here. ### Pathophysiology of IgA Nephropathy IgA nephropathy results from mesangial deposition of poorly galactosylated IgA1 immune complexes. Mucosal infections (respiratory or GI) trigger increased IgA production, leading to immune complex deposition in the glomerular mesangium, complement activation via the alternative/lectin pathway, and subsequent glomerular inflammation. **High-Yield:** Diagnosis is confirmed by renal biopsy showing mesangial IgA deposits on immunofluorescence. Treatment depends on proteinuria level and GFR trajectory; ACE inhibitors/ARBs are first-line for proteinuria >1 g/day. (Reference: Harrison's Principles of Internal Medicine, 21st ed.; Robbins & Cotran Pathologic Basis of Disease, 10th ed.)