IgA Nephropathy (IgAN)

A form of nephritic syndrome from deposition of IgA immune complexes in the glomeruli — the most common form of glomerulonephritis worldwide, and the leading cause of primary glomerulonephritis resulting in kidney failure in Australia (30% of primary-GN-caused kidney failure in 2020, per the ANZDATA registry — vs 5% of all new kidney failure overall, diabetic kidney disease being the largest single cause at 38%).

Epidemiology

• Onset at any age, peak in the teens/20s
• Affects men 2–6× more often than women
• More common in whites and Asians than Black populations; more common and more severe in people of Asian/Pacific descent specifically
• Prevalence of IgA kidney deposits: ~5% (US), 10–20% (southern Europe/Australia), 30–40% (Asia)

Clinical presentation

• Persistent/recurrent macroscopic haematuria, or asymptomatic microscopic haematuria with mild proteinuria
• Often presents after a mucosal/respiratory infection with haematuria lasting several days — gross haematuria typically begins 1–2 days after a febrile mucosal illness, mimicking post-streptococcal GN except the haematuria coincides with or immediately follows the febrile illness (rather than the ~1–3 week PSGN latency — see post-strep-glomerulonephritis.md)
• Flank pain and low-grade fever may accompany acute episodes
• Some patients are picked up incidentally via a hypertension work-up

When to suspect IgAN/GN and refer

Any combination of haematuria, hypertension, declining kidney function, or persistent proteinuria (± oedema) should raise suspicion for IgAN or another glomerulonephritis — refer to nephrology. Refer urgently if there are features of acute nephritis: rapid oedema onset, severe hypertension, gross haematuria, or rapid kidney function decline.

Any haematuria presentation should prompt an initial urine ACR check (see haematuria.md for the fuller assessment algorithm) — delayed referral is a recognised missed opportunity for early intervention, since progression can be subtle but ongoing.

Diagnosis

• Urinalysis: microscopic haematuria (usually dysmorphic RBCs, occasionally RBC casts); mild proteinuria (<1 g/day), which may occur without haematuria
• Renal biopsy confirms the diagnosis — granular IgA and complement (C3) deposition on immunofluorescence

Mild/asymptomatic IgAN — monitoring

Patients with asymptomatic microscopic haematuria, <100 RBC/HPF, normal renal USS/cytology/ renal function, no proteinuria and no hypertension typically have mild disease. Monitor 6-monthly: BP, eGFR, MSU, urine protein:creatinine ratio. All patients with IgAN — including mild cases — should be under regular nephrology follow-up, since progression can still occur even without overt proteinuria or symptoms, particularly with pre-existing CKD.

Risk factors for progression

Higher proteinuria at presentation, hypertension, and reduced renal function at diagnosis (creatinine clearance <75 mL/min) are the traditional risk factors — plus Asian/Pacific ethnicity (above).

Management

Best supportive care (KDIGO) is the cornerstone of therapy:

• Lifestyle: dietary sodium reduction, smoking cessation, weight management, exercise
• BP target 120–130/70 mmHg — tighter than the general CKD target of <130/80
• RAAS blockade at maximum tolerated dose for all patients with proteinuria >0.5 g/day, regardless of hypertension status

SGLT2 inhibitors (dapagliflozin, empagliflozin) are now an additional foundational therapy — DAPA-CKD and EMPA-KIDNEY showed substantial progression-slowing benefit in non-diabetic CKD including IgAN. PBS authority-listed for CKD with eGFR 25–75 mL/min/1.73m² and uACR 22.6–565 mg/mmol, if already stabilised on RAAS blockade for at least 4 weeks.

Newer IgAN-specific, non-immunosuppressive options for patients at risk of progression:

• Targeted-release budesonide (Tarpeyo) — acts on gut mucosal immunity; approved by several regulators 2021–2023
• Sparsentan — a dual endothelin/angiotensin receptor antagonist, FDA-approved 2023

Corticosteroids remain a cornerstone for high-risk patients with persistent proteinuria despite optimal supportive care — reduce proteinuria and delay progression, but carry significant adverse-effect risk (including severe infection). Corticosteroids and cyclophosphamide are used for proliferative injury or rapidly progressive GN. Transplantation for advanced disease.

Prognosis

• Usually progresses slowly: renal insufficiency and hypertension develop within 10 years in 15–20% of patients; progression to end-stage renal disease occurs in 25% by 20 years
• Childhood-diagnosed IgAN usually has a good prognosis, though persistent haematuria invariably leads to hypertension, proteinuria and renal insufficiency over time
• Risk factors for progressive deterioration: proteinuria >1 g/day, elevated creatinine, uncontrolled hypertension, persistent microscopic haematuria, extensive fibrotic change, crescents on biopsy