Acute and chronic glomerulonephritis

At a glance

• Glomerulonephritis (GN) is inflammation of the glomeruli. It presents on a spectrum from isolated microscopic haematuria to nephritic syndrome to rapidly progressive GN (RPGN).
• Acute GN develops over days to weeks. Chronic GN is persistent haematuria and proteinuria with slowly declining GFR over years, often found on a routine urine test.
• Dysmorphic red cells and red cell casts locate the bleeding to the glomerulus.
• Complement levels split the causes into low-complement and normal-complement groups.
• Treat every patient with supportive kidney protection (BP, RAS blockade, SGLT2 inhibitor), and add immunosuppression for the specific lesion.

Classification

Syndrome	Features
Asymptomatic haematuria	Microscopic haematuria, normal GFR, minimal proteinuria. IgA nephropathy, thin basement membrane nephropathy, Alport syndrome
Nephritic syndrome	Haematuria with casts, proteinuria under 3.5 g/day, hypertension, oedema, reduced GFR
RPGN	Loss of half the GFR over days to weeks, crescents on biopsy. See Rapidly progressive glomerulonephritis
Nephrotic syndrome	Proteinuria over 3.5 g/day, albumin under 30 g/L, oedema. See Oedema
Chronic GN	Persistent active sediment, proteinuria and progressive CKD

Many lesions overlap: lupus nephritis and MPGN can be nephritic and nephrotic at once.

Causes

Complement	Causes
Low C3, normal C4	Post-infectious GN (including post-streptococcal), C3 glomerulopathy
Low C3 and C4	Lupus nephritis, cryoglobulinaemia (C4 very low; hepatitis C), immune-complex MPGN, infective endocarditis, shunt nephritis
Normal	IgA nephropathy, IgA vasculitis, ANCA-associated GN, anti-GBM disease, thin basement membrane and Alport syndrome

Recognition

• Urine: cola-coloured or frank haematuria, frothy urine.
• Volume: periorbital and leg oedema, hypertension, sometimes pulmonary oedema from salt and water retention.
• Systemic clues: rash, arthritis, serositis (lupus); purpura over the legs and buttocks, abdominal pain (IgA vasculitis); haemoptysis (anti-GBM, ANCA); sinus disease (GPA); fever and murmur (endocarditis); recent impetigo or sore throat.

The important individual diseases

IgA nephropathy

• The commonest primary GN worldwide and in Australia. Peaks in young adults.
• Episodic visible haematuria within 1 to 3 days of an upper respiratory infection (synpharyngitic), or persistent microscopic haematuria with proteinuria.
• Diagnosis needs a biopsy (mesangial IgA deposits). The Oxford MEST-C score and the International IgAN Prediction Tool estimate the risk of kidney failure.
• About 20 to 40% reach kidney failure within 20 years. Proteinuria is the strongest modifiable predictor.

Post-infectious GN (including post-streptococcal)

• Follows group A streptococcal infection: 1 to 3 weeks after pharyngitis or 3 to 6 weeks after skin infection.
• In remote Aboriginal and Torres Strait Islander communities, impetigo driven by scabies causes recurrent outbreaks. Post-streptococcal GN in childhood is linked to adult CKD in these communities.
• Raised ASOT (after pharyngitis) or anti-DNase B (better after skin infection), low C3.
• In older adults, post-infectious GN increasingly follows staphylococcal infection, often in diabetes, and may show IgA-dominant deposits.
• Children usually recover with supportive care. Adults do worse.

Lupus nephritis

• Up to half of people with SLE develop nephritis, most within 5 years of diagnosis. Screen with urinalysis and UPCR at each review.
• ISN/RPS classes: I and II mesangial, III focal and IV diffuse proliferative (need immunosuppression), V membranous (nephrotic), VI advanced sclerosis.
• Low C3 and C4 and rising anti-dsDNA track activity.

Others

• IgA vasculitis (Henoch-Schönlein purpura): purpura, arthralgia, abdominal pain and IgA nephritis. Self-limiting in most children; adults have worse kidney outcomes.
• Cryoglobulinaemic GN: hepatitis C, purpura, arthralgia, neuropathy, very low C4, positive rheumatoid factor.
• Infective endocarditis: immune-complex GN with low complement. Treat the infection. See Infective endocarditis.
• Alport syndrome (COL4A3 to COL4A5, X-linked in most): haematuria, sensorineural deafness, anterior lenticonus. Not inflammatory but often in the haematuria differential.

Investigations

• Urine: dipstick, phase-contrast microscopy for dysmorphic red cells (acanthocytes) and casts, UPCR or UACR. CARI 2025 notes KDIGO's preference for timed collections when an exact measure matters.
• Kidney function: creatinine and eGFR, with trend.
• Serology: C3, C4, ANA and anti-dsDNA, ANCA (MPO and PR3), anti-GBM, ASOT and anti-DNase B, hepatitis B and C, HIV, cryoglobulins, rheumatoid factor.
• Over 50 or unexplained: serum protein electrophoresis with immunofixation, serum free light chains and urine immunofixation (the IKMG screen) for monoclonal gammopathy of renal significance.
• Blood cultures when endocarditis is possible.
• Kidney ultrasound for size and to plan biopsy.
• Kidney biopsy is the diagnostic standard: light microscopy, immunofluorescence and electron microscopy. Typical post-streptococcal GN in a child with recovering C3 usually doesn't need one.

Management

Supportive care for all

• BP target: systolic under 120 mmHg where tolerated (KDIGO 2021 BP in CKD); 120/70 or lower in IgA nephropathy (KDIGO 2025).
• ACE inhibitor or ARB titrated to the maximum tolerated dose for proteinuria. Check creatinine and potassium at 1 to 2 weeks; a rise in creatinine under 30% is acceptable.
• SGLT2 inhibitor: DAPA-CKD and EMPA-KIDNEY included many patients with GN and showed slower progression. Both dapagliflozin and empagliflozin are PBS-listed for CKD.
• Salt restriction under 2 g sodium/day, statins for persistent nephrotic-range proteinuria or high cardiovascular risk, avoid NSAIDs.
• Vaccinate before immunosuppression; screen for hepatitis B, latent TB and strongyloides where relevant.

IgA nephropathy (KDIGO 2025)

• Biopsy and treat if proteinuria is over 0.5 g/day (the 2021 threshold was 1 g/day).
• Targets: proteinuria under 0.5 g/day, ideally under 0.3 g/day, and eGFR loss under 1 mL/min/year.
• The new framework treats two things at once: the IgA immune process and the nephron loss it causes.
  • Nephron loss: maximal RAS blockade or sparsentan (dual endothelin and angiotensin receptor antagonist; PROTECT), plus an SGLT2 inhibitor.
  • Immune process: a 9-month course of targeted-release budesonide (Nefecon; NefIgArd) for those at risk of progression. If unavailable, reduced-dose methylprednisolone 0.4 mg/kg/day for 2 months then tapering (TESTING), with PJP prophylaxis.
• In September 2025, CARI noted targeted-release budesonide and sparsentan weren't yet approved or subsidised in Australia and New Zealand, so access depended on trials or special access. An ARTG search in November 2026 still found neither product, so access remains through trials or special access.
• Rapidly progressive IgA nephropathy is treated like ANCA vasculitis (cyclophosphamide and glucocorticoids).

Post-streptococcal GN

• Supportive: salt and fluid restriction, loop diuretics for overload, antihypertensives, dialysis if needed.
• Penicillin treats ongoing streptococcal infection and protects contacts. It doesn't change the course of the GN.
• Treat scabies and impetigo in the household. Public health units coordinate response to community outbreaks in the NT, WA, SA and Queensland.

Lupus nephritis (KDIGO 2024, EULAR 2025)

• Hydroxychloroquine for all patients unless contraindicated.
• Class III or IV induction: glucocorticoids (IV methylprednisolone pulses then reduced-dose oral prednisolone, tapering to 7.5 mg/day or less by 3 to 6 months) plus one of:
  • mycophenolate (MMF 2 to 3 g/day)
  • low-dose IV cyclophosphamide (Euro-Lupus: 500 mg every 2 weeks for 6 doses)
  • mycophenolate plus belimumab (BLISS-LN)
  • mycophenolate plus a calcineurin inhibitor (voclosporin, AURORA; or tacrolimus) when eGFR is over 45
• EULAR 2025 goes further, favouring early add-on therapy for many patients. Obinutuzumab added to standard therapy raised complete renal response at week 76 (46% versus 33%, REGENCY, NEJM 2025).
• Maintenance with mycophenolate for at least 3 years in total. Azathioprine if planning pregnancy (mycophenolate is teratogenic; stop it 6 weeks before conception).
• Complete response: UPCR under 50 mg/mmol with stable eGFR within 12 months.

Complications

• AKI and RPGN, CKD and kidney failure.
• Hypertension and accelerated cardiovascular disease.
• Nephrotic complications: VTE, infection, hyperlipidaemia.
• Treatment toxicity: infection (PJP), steroid diabetes and osteoporosis, cyclophosphamide infertility and bladder toxicity.
• Recurrence after transplant, especially IgA nephropathy, C3 glomerulopathy and FSGS.

Pitfalls

• Mistaking catheter or menstrual blood for glomerular haematuria. Repeat the urine and look at the cells.
• Calling post-streptococcal GN without checking C3 recovery at 8 weeks.
• Forgetting hepatitis C serology in GN with very low C4 and purpura.
• Missing monoclonal gammopathy in older adults with proteinuric kidney disease.
• Using the old IgA threshold of 1 g/day: KDIGO 2025 acts at 0.5 g/day.
• Starting mycophenolate in a woman of reproductive age without contraception counselling.