Synopsis
Recognise membranous nephropathy, separate primary immune disease from secondary causes, and coordinate risk-based supportive and specialist treatment safely.
- Membranous nephropathy is an immune-complex glomerular disease in which subepithelial deposits and podocyte injury produce heavy, often nephrotic-range proteinuria.
- Anti-PLA2R antibodies strongly support primary membranous nephropathy in the right phenotype, but a negative result neither excludes the disease nor removes the need to search for secondary causes.
- Evaluate medicines, malignancy, hepatitis B and C, autoimmune disease and other clinical clues before calling a case primary; biopsy antigen staining may refine this assessment.
- Natural history varies from spontaneous remission to persistent nephrosis and kidney failure, so treatment intensity should follow proteinuria, eGFR trajectory, antibody activity and complications rather than one urine result.
- Supportive care includes renin–angiotensin system blockade when tolerated, blood-pressure control, salt advice, oedema management, cardiovascular prevention and prompt infection assessment.
- Thrombosis risk rises with severe nephrosis and low albumin, but prophylactic anticoagulation is an individual benefit–bleeding decision rather than an automatic albumin threshold.
- Immunosuppression belongs in a nephrology pathway after secondary causes and treatment hazards have been addressed; rituximab access and regimen require current NHS and local governance.
- Clinical remission can lag behind immunological improvement, while rising or persistent anti-PLA2R may precede continuing disease activity and should be interpreted longitudinally.
Key red flags
Sudden pleuritic pain, hypoxia, unilateral leg swelling or loin pain may indicate pulmonary, deep venous or renal-vein thrombosis.
Active urinary casts, systemic inflammation or a rapid creatinine rise should prompt consideration of superimposed crescentic disease, infection or another diagnosis.
Fever or focal symptoms in nephrotic or immunosuppressed patients warrant prompt assessment because urinary immunoglobulin loss and treatment both increase risk.
Investigation priorities
Quantify protein loss and identify blood or an active sediment.
Management branches
An adult has heavy albuminuria with suspected nephrotic syndrome.
- Confirm quantitative proteinuria, serum albumin, renal trajectory and clinical complications while reviewing previous results.
- Request anti-PLA2R and a history-led secondary screen, including prescribed and non-prescribed medicines, infection risks and malignancy symptoms.
- Discuss biopsy with nephrology when serology is negative or discordant, renal function falls, another lesion is plausible, or tissue classification will guide treatment.
Membranous nephropathy is likely or confirmed and the patient is clinically stable.
- Optimise blood pressure and antiproteinuric therapy cautiously, checking creatinine and potassium after renin–angiotensin system changes.
- Treat oedema with salt advice and individually titrated diuresis while avoiding intravascular depletion, hypotension and avoidable acute kidney injury.
- Assess thrombosis and bleeding risks explicitly; investigate symptoms urgently and seek specialist advice before prophylactic anticoagulation.
Key medicines
ACE inhibitor or angiotensin-receptor blockerSelect and titrate one agent using the current CKD formulary, blood pressure, potassium and eGFR; do not combine ACE inhibition with an ARB.Check renal function and potassium after initiation and dose changes. Pause or reassess during significant hypovolaemia, marked hypotension, hyperkalaemia or a disproportionate creatinine rise, and follow pregnancy contraindications.
Rituximab in selected primary diseaseUse only through the specialist membranous-nephropathy protocol and current NHS commissioning arrangements; regimen, premedication and retreatment are determined by the renal team.Screen for hepatitis B and other infection risks, review vaccination timing, immunoglobulins and prior reactions, and counsel about delayed infection and reproductive considerations. Do not copy a regimen from another autoimmune indication.