A 35-year-old woman from Delhi presents with a 1-week history of gross haematuria, facial swelling, and headache. She denies fever, rash, or joint pain. BP is 172/104 mmHg. Urine shows 4+ blood, 2+ protein, and RBC casts. Serum creatinine is 2.1 mg/dL (baseline 0.9), and serum albumin is 3.8 g/dL. Serologies: ANA negative, anti-GBM negative, ANCA negative. Complement C3 is normal. Renal ultrasound shows normal-sized kidneys with increased echogenicity. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: IgA Nephropathy ### Key Clinical Features **Key Point:** IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and the most common cause of nephritic syndrome in East Asia and the Mediterranean. This patient presents with: 1. **Acute nephritic syndrome** — gross haematuria, hypertension, acute kidney injury (creatinine 2.1) 2. **Absence of systemic features** — no fever, rash, arthritis, or constitutional symptoms 3. **Negative serologies** — ANA, anti-GBM, ANCA all negative; **normal C3 complement** 4. **Urinary findings** — RBC casts (indicating glomerular origin of haematuria) ### Diagnostic Criteria Met | Feature | Finding | Significance | |---------|---------|---------------| | **Presentation** | Gross haematuria, hypertension | Acute nephritic pattern | | **Serum creatinine** | 2.1 (baseline 0.9) | Acute kidney injury | | **Urine** | 4+ blood, 2+ protein, RBC casts | Glomerulonephritis | | **C3 complement** | Normal | Rules out post-infectious or lupus nephritis | | **ANA, anti-GBM, ANCA** | All negative | Rules out lupus, anti-GBM disease, vasculitis | | **Systemic features** | Absent | Primary glomerulonephritis, not secondary | ### Pathophysiology **High-Yield:** IgA nephropathy is characterized by **predominant IgA deposition on immunofluorescence microscopy** (gold standard for diagnosis). The mechanism involves: 1. Abnormal IgA1 glycosylation → reduced clearance 2. Circulating IgA1-dominant immune complexes 3. Glomerular deposition → complement activation (alternative pathway) 4. Proliferative glomerulonephritis on light microscopy **Mnemonic: IgAN features — HEMATURIA** - **H**aematuria (gross or microscopic) - **E**ast Asia endemic - **M**ost common primary GN worldwide - **A**bsence of systemic disease - **T**ypically young adults - **U**rinary RBC casts - **R**enal biopsy diagnostic (IgA deposits) - **I**mmunofluorescence shows IgA predominance - **A**lternative complement pathway activation ### Clinical Variants 1. **Episodic haematuria** (most common) — recurrent gross haematuria with upper respiratory infections 2. **Persistent microscopic haematuria** — proteinuria ± declining renal function 3. **Rapidly progressive** — rare, with crescent formation ### Prognosis **Clinical Pearl:** IgAN has variable outcomes; ~30% progress to end-stage renal disease over 20 years. Factors predicting poor prognosis include: - Proteinuria >1 g/day - Hypertension - Reduced GFR at presentation - Crescentic disease on biopsy ### Management - **Supportive:** ACE inhibitor/ARB (renal protective, reduces proteinuria) - **Blood pressure control:** target <120/80 mmHg - **Corticosteroids:** considered for progressive disease or proteinuria >1 g/day - **Immunosuppression:** reserved for crescentic or rapidly progressive IgAN - **Definitive diagnosis:** renal biopsy with immunofluorescence (IgA predominance) **Key Point:** This patient requires renal biopsy to confirm IgAN and assess for crescents, which would influence treatment intensity.