A 28-year-old man from rural India presents with cola-coloured urine and facial puffiness for 3 days. He reports a sore throat 2 weeks prior. On examination: BP 148/92 mmHg, periorbital oedema, no rash. Urinalysis shows RBC casts, proteinuria (2.1 g/day), and dysmorphic RBCs. Serum creatinine 1.2 mg/dL, ASO titre elevated. Complement C3 is low; C4 normal. Renal biopsy shows IgA-dominant deposits on immunofluorescence. What is the most likely diagnosis?

Explanation

## Clinical Presentation & Diagnosis **Key Point:** IgA nephropathy (Berger's disease) is defined by **IgA-dominant mesangial deposits** on immunofluorescence — this is the pathognomonic and definitive finding that establishes the diagnosis, overriding all other clinical clues. ### Diagnostic Features in This Case | Feature | Finding | Significance | |---------|---------|--------------| | **Renal biopsy IF** | IgA-dominant deposits | **Pathognomonic for IgA nephropathy** — the single most important finding | | **Trigger** | Sore throat 2 weeks prior | IgA nephropathy classically follows mucosal infections; latency can be short (synpharyngitic) or longer | | **Clinical syndrome** | Cola urine, RBC casts, dysmorphic RBCs, proteinuria | Acute nephritic presentation consistent with IgA nephropathy | | **Complement profile** | Low C3, normal C4 | Seen in IgA nephropathy (alternative pathway activation); NOT exclusive to PSGN | | **ASO titre** | Elevated | Confirms recent streptococcal exposure but does NOT determine the biopsy diagnosis | | **Age/setting** | 28-year-old male | IgA nephropathy is the most common primary GN worldwide, peak in 2nd–3rd decade | **High-Yield:** The immunofluorescence finding is the **gold standard** for diagnosing glomerulonephritis. IgA-dominant mesangial deposits = IgA nephropathy by definition (Robbins 10e, Ch 20). PSGN classically shows **granular IgG + C3** ("starry sky") deposits — NOT IgA-dominant deposits. ### Why Not the Other Options? - **B) PSGN:** Classic IF shows granular IgG and C3 deposition, NOT IgA-dominant. Although ASO titre and low C3 suggest streptococcal exposure, the biopsy result is definitive and incompatible with PSGN. - **A) Lupus nephritis:** Would show "full house" immunofluorescence (IgG, IgA, IgM, C3, C4, C1q). C4 is normal here, making lupus nephritis unlikely. - **C) MPGN:** Shows C3 ± IgG deposits with a membranoproliferative pattern on light microscopy; not IgA-dominant. **Clinical Pearl:** IgA nephropathy can mimic PSGN clinically (post-infectious nephritic syndrome, low C3, elevated ASO), but the renal biopsy is the definitive arbiter. In IgA nephropathy, episodes of gross haematuria often occur **synpharyngitically** (within 1–2 days of infection) or with a longer latency, and the disease follows a relapsing-remitting course unlike the self-limited PSGN. ### Management of IgA Nephropathy 1. **ACE inhibitors / ARBs** — first-line for proteinuria and hypertension control 2. **Fish oil (omega-3 fatty acids)** — may slow progression in proteinuric patients 3. **Corticosteroids** — considered if proteinuria >1 g/day despite RAS blockade 4. **Tonsillectomy** — debated; may reduce recurrent episodes in some patients 5. **Avoid nephrotoxins**; monitor renal function regularly [cite: Robbins & Cotran Pathologic Basis of Disease, 10e, Ch 20; Harrison's Principles of Internal Medicine, 21e, Ch 308]