Lucan · Conditions

Glomerulonephritis approach

Australian guidance: CARI Guidelines — Glomerulonephritis

1. Definition and epidemiology

Glomerulonephritis (GN) refers to a heterogeneous group of immune-mediated disorders characterised by inflammation of the glomerulus, leading to haematuria, proteinuria, and variable degrees of renal impairment. In Australia, glomerular disease accounts for 18% of all causes of kidney failure, making it the second most common identifiable cause behind diabetic kidney disease (40%), as documented by Kidney Health Australia. GN spans a spectrum from asymptomatic urinary abnormalities to rapidly progressive glomerulonephritis (RPGN), which constitutes a renal emergency requiring urgent nephrologist review.

2. Pathophysiology

Per Robbins Ch 20, glomerular injury occurs via two main immune mechanisms. First, immune complex deposition: circulating antigen-antibody complexes lodge in the glomerular basement membrane (GBM) or mesangium, activating complement (C3, C4) and triggering neutrophil and macrophage recruitment. This produces the granular immunofluorescence pattern seen in post-infectious GN, lupus nephritis, and IgA nephropathy. Second, anti-GBM disease (Goodpasture syndrome): autoantibodies against the alpha-3 chain of type IV collagen bind directly to the GBM, producing a linear immunofluorescence pattern and frequently causing RPGN with pulmonary haemorrhage. A third pauci-immune mechanism occurs in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis): little or no immunoglobulin deposition is found, yet necrotising crescentic GN develops. Crescents form from proliferating parietal epithelial cells and macrophages filling Bowman's space, compressing the glomerular tuft and causing rapid loss of filtration function.

3. Clinical presentation and diagnostic criteria

GN classically presents as one of several clinical syndromes. The nephritic syndrome features haematuria (dysmorphic red cells, red cell casts on microscopy), subnephrotic proteinuria, hypertension, and oliguria with reduced glomerular filtration rate (GFR). The nephrotic syndrome features heavy proteinuria (greater than 3.5 g per day in adults), oedema, hypoalbuminaemia, and hyperlipidaemia, and points toward minimal change disease, focal segmental glomerulosclerosis, or membranous nephropathy. RPGN presents with rapid deterioration in renal function (often a doubling of creatinine within weeks), frequently with active urinary sediment; it requires same-day nephrologist review. Asymptomatic haematuria with or without proteinuria is the most common presentation of IgA nephropathy, the most prevalent primary GN worldwide. The CARI CKD staging guideline explicitly identifies RPGN and vasculitis as treatable causes to exclude when evaluating any new CKD presentation.

4. Investigations and AU-specific cutoffs

Initial investigations follow the Kidney Health Australia algorithm for CKD evaluation, adapted for suspected GN:

Always indicated: - Serum urea, electrolytes, creatinine and eGFR (repeat within 1 week if eGFR less than 60 mL/min/1.73m2 to exclude acute kidney injury) - Urine albumin-to-creatinine ratio (uACR): first morning void preferred; AU cutoffs are uACR less than 3.0 mg/mmol (A1, normal), 3.0 to 30 mg/mmol (A2, microalbuminuria), greater than 30 mg/mmol (A3, macroalbuminuria) - Urine microscopy: dysmorphic red cells and red cell casts confirm glomerular origin of haematuria - Full blood count, fasting lipids, glucose, LFTs, hsCRP, ESR - Renal ultrasound of kidneys, ureters, and bladder (KUB) at least once

Conditionally indicated (when GN is suspected or there are signs of systemic disease): - Anti-GBM antibody: when pulmonary symptoms, haemoptysis, or rapidly deteriorating renal function are present - ANCA (c-ANCA/PR3, p-ANCA/MPO): when systemic vasculitis features (rash, arthritis, sinusitis, lung involvement) or RPGN pattern are present - Antinuclear antibodies (ANA) and extractable nuclear antigens (ENA): for suspected lupus nephritis - Complement studies (C3, C4): low complement in post-infectious GN, lupus, membranoproliferative GN; normal in IgA nephropathy and ANCA vasculitis - HBV, HCV, and HIV serology: risk-factor directed, given their association with membranous nephropathy and membranoproliferative GN - Serum and urine protein electrophoresis and free light chains: to exclude myeloma-associated renal disease - Renal biopsy: indicated when persistent uACR greater than 60 to 120 mg/mmol (approximately equivalent to urinary protein greater than 1 to 2 g/day), or when the GN subtype would alter treatment

5. Management

Management is disease-specific and directed by biopsy histology; general principles follow CARI and KHA guidance.

Blood pressure control: Target below 130/80 mmHg for all patients with GN-associated CKD, particularly those with proteinuria, where this lower target has been associated with reduced progression. The CARI cardiovascular guideline recommends a target below 130/80 mmHg specifically in individuals with CKD and macroalbuminuria.

Renin-angiotensin-aldosterone system (RAAS) blockade: ACE inhibitors (ACEi) or angiotensin receptor blockers (ARBs) are preferred as first-line antihypertensive agents in patients with proteinuric GN, given evidence of cardiovascular and renoprotective benefit. Dual RAAS blockade (combining ACEi with ARB or a renin inhibitor) is not recommended due to increased adverse outcomes without additional proven benefit.

Immunosuppression (disease-specific): - IgA nephropathy: ACEi or ARB for proteinuria reduction; oral corticosteroids (prednisolone) considered if proteinuria persists above 1 g/day after 3 to 6 months of optimised supportive care - Minimal change disease: high-dose prednisolone (1 mg/kg/day up to 80 mg/day) is first-line; cyclophosphamide or calcineurin inhibitors for relapsing or steroid-dependent disease - Membranous nephropathy: conservative management with RAAS blockade for low-risk disease; cyclophosphamide with alternating corticosteroids (Ponticelli regimen) or rituximab for high-risk or progressive disease - RPGN from ANCA vasculitis: urgent high-dose corticosteroids combined with cyclophosphamide or rituximab, with or without plasma exchange depending on severity - Anti-GBM disease: urgent plasma exchange, high-dose corticosteroids, and cyclophosphamide

Lifestyle: Dietary salt restriction to less than 5 g per day, target BMI below 25 kg/m2, and avoidance of nephrotoxic agents (NSAIDs, contrast without renal precautions) apply to all patients.

6. Pharmacology and AU PBS notes

First-line: - ACEi (e.g. perindopril, ramipril, enalapril) or ARB (e.g. irbesartan, losartan, candesartan): PBS listed for hypertension and for diabetic nephropathy (irbesartan PBS streamlined code 4141 for type 2 diabetes with microalbuminuria). In non-diabetic proteinuric GN, these agents are prescribed on clinical grounds as their renoprotective benefit is well established but PBS subsidy is under standard hypertension or heart failure indications. - Prednisolone (AU brand: various generics): PBS listed for nephrotic syndrome and vasculitis indications. - Fludrocortisone is not used for GN.

Second-line / disease-modifying: - Cyclophosphamide (PBS listed for vasculitis and some glomerular conditions) - Rituximab (PBS streamlined codes available for ANCA vasculitis: code 8512 induction; requires prior cyclophosphamide or documented intolerance in some scenarios) - Mycophenolate mofetil (used as maintenance therapy in lupus nephritis; PBS listed for transplant, used off-label for lupus nephritis) - Calcineurin inhibitors (ciclosporin, tacrolimus): used in steroid-dependent or frequently relapsing nephrotic syndrome; PBS listed for transplant, often off-label in GN

Supportive: - Statins: no specific cholesterol target in CKD, but statin with or without ezetimibe is recommended when eGFR is at least 15 mL/min/1.73m2 and 10-year cardiovascular disease risk is at least 10%, consistent with KHA guidance - Loop diuretics (frusemide): for oedema in nephrotic syndrome

7. Complications and monitoring

Complications: - Progression to CKD and end-stage kidney disease: glomerular disease causes 18% of kidney failure in Australia; risk correlates with proteinuria burden and hypertension control - Cardiovascular disease: CKD patients are up to 20 times more likely to die from cardiovascular events than to reach dialysis; this risk applies proportionally to GN-related CKD - Thromboembolic disease: nephrotic syndrome increases clotting factor synthesis and reduces anticoagulant proteins, predisposing to deep venous thrombosis and renal vein thrombosis (particularly in membranous nephropathy) - Infection: immunosuppression increases infection risk; live vaccine administration is contraindicated during active immunosuppression - Hypertension and secondary hyperparathyroidism with progressive CKD - Anaemia of CKD (typically apparent when eGFR falls below 45 mL/min/1.73m2)

Monitoring schedule: - eGFR and uACR: 3 monthly in active or progressive GN; 6 to 12 monthly once stable - Blood pressure at every clinical encounter; target below 130/80 mmHg - Urine microscopy: repeat to assess for persistent red cell casts indicating ongoing glomerular inflammation - Electrolytes (potassium, bicarbonate) when on ACEi or ARB and eGFR below 45 - Complement levels (C3, C4) and anti-dsDNA antibody titre for lupus nephritis monitoring - ANCA titres for monitoring vasculitis activity and guiding immunosuppression tapering - Vaccination: influenza annually, pneumococcal (initial and booster), COVID-19, and herpes zoster for patients aged 65 years and over or those who are immunocompromised - Nephrology referral: indicated at eGFR below 30 mL/min/1.73m2, a 20% or greater decline in eGFR over 3 months, or any suspicion of an immune-mediated or rapidly progressive GN

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.