IgA Nephropathy

IgA nephropathy is the commonest primary glomerulonephritis worldwide, defined by dominant mesangial IgA deposition.

• Highest prevalence in East Asia and Europe, lower in people of African ancestry; peak onset in 2nd to 3rd decade, male predominance.
• Pathogenesis ("four hit"): galactose-deficient IgA1 (hit 1), autoantibodies against it (2), immune complex formation (3), mesangial deposition with complement activation and inflammation (4).
• Genetic associations (HLA, CFH region); mucosal immune dysregulation.
• Secondary causes: cirrhosis, coeliac disease, HIV, inflammatory bowel disease, ankylosing spondylitis.
• Prognosis: 20 to 40% develop ESKD in 20 years. Adverse factors: proteinuria over 1 g/day, hypertension, reduced GFR, MEST-C lesions (mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, tubular atrophy, crescents).

• Recurrent macroscopic haematuria 1 to 3 days after an upper respiratory infection (synpharyngitic), with loin pain.
• Persistent microscopic haematuria with proteinuria found incidentally.
• Hypertension, nephrotic syndrome (minority), rapidly progressive GN with crescents, AKI from red cell cast nephropathy.
• Chronic kidney disease at presentation in 20%.

• Urinalysis: dysmorphic red cells, red cell casts, proteinuria; creatinine and eGFR; normal complement (C3 may be reduced in some).
• Renal biopsy: mesangial IgA-dominant deposits with C3, mesangial proliferation; Oxford MEST-C classification. Indicated with proteinuria over 0.5 g/day, reduced GFR or unclear diagnosis.
• Exclude IgA vasculitis (extra-renal features), lupus nephritis, post-infectious GN, Alport syndrome, thin basement membrane disease, secondary IgA nephropathy.
• Serum IgA elevated in 50%; routine serology for hepatitis B/C, HIV, ANA.
• Risk assessment with the international IgAN prediction tool.

• Optimised supportive care for all for at least 3 months: ACE inhibitor or ARB titrated to maximum (ramipril 10 mg, losartan 100 mg), blood pressure below 120/80 mmHg, sodium restriction, SGLT2 inhibitor (dapagliflozin 10 mg or empagliflozin 10 mg), statin, weight loss, smoking cessation, avoid NSAIDs.
• Persistent proteinuria over 1 g/day despite supportive care and eGFR above 30 mL/min:
  • Targeted release budesonide 16 mg daily for 9 months, then 8 mg for 2 weeks (reduces proteinuria and slows eGFR decline).
  • Systemic glucocorticoids: methylprednisolone 0.8 to 1 mg/kg (maximum 80 mg) tapered over 6 to 9 months, with significant infection risk (low dose regimens preferred; use Pneumocystis prophylaxis and bone protection).
  • Sparsentan 400 mg daily (dual endothelin and angiotensin receptor antagonist), or atrasentan 0.75 mg daily.
  • Iptacopan 200 mg twice daily (factor B inhibitor).
  • Sibeprenlimab and other APRIL inhibitors emerging.
• Crescentic IgAN with rapid decline: methylprednisolone 500 mg to 1 g IV for 3 days with cyclophosphamide 15 mg/kg or rituximab.
• Hydroxychloroquine 200 to 400 mg daily may reduce proteinuria. Mycophenolate in selected Asian patients with active lesions.
• Tonsillectomy is not recommended in Western populations.
• Monitor eGFR and urine protein every 3 to 6 months; transplantation (recurrence in 30 to 50%, rarely graft loss).