In New Zealand, membranous Nephropathy is managed by nephrologists. Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in non-diabetic adults of European ancestry, accounting for roughly 20-30% of biopsy-proven adult nephrotic syndrome. It is driven by deposition of subepithelial immune complexes on the outer surface of the glomerular basement membrane, with thickening visible on light microscopy and characteristic spikes on silver staining.
Membranous nephropathy (ICD-10: N04.2 nephrotic syndrome with diffuse membranous glomerulonephritis) is a histologic pattern of glomerular disease defined by subepithelial immune complex deposits on the glomerular basement membrane (GBM), with diffuse thickening of the GBM and characteristic spikes seen on Jones silver stain. The cellular mechanism involves IgG4-predominant autoantibodies binding to a podocyte antigen — most commonly the M-type phospholipase A2 receptor (PLA2R), responsible for 70-80% of primary cases — at the podocyte slit diaphragm. Bound antibody activates the complement membrane attack complex (C5b-9) in situ, damaging podocytes and producing massive proteinuria. Newer antigens include thrombospondin type-1 domain-containing 7A (THSD7A, 1-5%), neural epidermal growth factor-like 1 protein (NELL1, particularly in malignancy-associated MN), semaphorin 3B, protocadherin 7, and exostosin 1/2 (in lupus-associated cases).
The key symptoms of Membranous Nephropathy are: Foamy, frothy urine that persists from morning to evening — the visible expression of heavy proteinuria., Generalized peripheral edema, often starting in the ankles and progressing to the thighs, scrotum or vulva, and abdomen; periorbital edema is common in the morning., Sudden weight gain (5-15 kg) from fluid retention over weeks to months., Fatigue and reduced exercise tolerance from hypoalbuminemia and overall systemic effects of nephrotic syndrome., Sometimes hypertension (40-50% of patients at presentation) with associated headache or blurred vision., Microscopic hematuria in roughly 30-50% of patients; macroscopic hematuria is uncommon and suggests a different diagnosis., Symptoms of venous thromboembolism — unilateral leg swelling with calf tenderness, pleuritic chest pain, breathlessness, or flank pain — from renal-vein thrombosis or deep-vein thrombosis, particularly in severe nephrotic syndrome..
Diagnosis starts with confirmation of nephrotic syndrome — proteinuria over 3.5 g/24 hours (or urinary protein-to-creatinine ratio over 3.5 g/g) with hypoalbuminemia under 30 g/L, edema, and hyperlipidemia. Serum and urine immunofixation rules out paraprotein-associated disease. Hepatitis B and C serology, HIV testing, autoimmune panel (ANA, anti-dsDNA, complement C3 and C4, anti-Ro, anti-La, anti-thyroid), serum anti-PLA2R antibody, age-appropriate cancer screening, and review of medications all proceed in parallel. Anti-PLA2R antibody by indirect immunofluorescence or ELISA is positive in 70-80% of primary MN and is approximately 99% specific. A positive anti-PLA2R titer combined with nephrotic syndrome and absence of secondary causes can sometimes confirm primary MN without biopsy (KDIGO 2021), but renal biopsy remains the gold standard. Biopsy shows diffuse subepithelial immune deposits on electron microscopy with characteristic GBM spikes, granular IgG (predominantly IgG4 in primary disease, IgG1/IgG3 in secondary or lupus-associated) and C3 on immunofluorescence, and positive PLA2R or THSD7A staining when applicable. Disease stages (Ehrenreich-Churg I to IV) reflect deposit location and basement membrane thickening. Risk stratification at diagnosis uses proteinuria magnitude, serum albumin, eGFR, anti-PLA2R titer, and rate of change — KDIGO 2021 separates low, moderate, high, and very-high risk to guide treatment. Imaging (renal ultrasound) excludes obstruction and assesses kidney size; chest CT, colonoscopy, mammography, and PSA are obtained based on age and risk profile.
Outlook in MN follows the rule of thirds without treatment but is substantially better with risk-stratified KDIGO-aligned care. Low-risk patients have spontaneous complete or partial remission rates of 30-35% within 12-24 months. With immunosuppression, complete or partial remission is achieved in 60-80% of moderate-to-high-risk patients. Long-term renal survival at 10 years exceeds 80% in patients achieving sustained remission, versus 35-50% in those with persistent nephrotic-range proteinuria. The MENTOR trial showed sustained remission at 24 months in 60% on rituximab versus 20% on cyclosporine, with similar safety. Predictors of poor outcome include male sex, older age, severe baseline proteinuria over 8 g/day, declining eGFR, high anti-PLA2R titer, and chronic damage on biopsy (interstitial fibrosis over 25%). Recurrence after transplantation occurs in approximately 40% of primary MN recipients and is treated effectively with rituximab. Cardiovascular and thromboembolic complications remain significant contributors to morbidity and mortality and require integrated management.
Nephrology referral is essential for any adult with nephrotic-range proteinuria. Specialists confirm diagnosis with biopsy, identify secondary causes, perform risk stratification, and select immunosuppression. Tertiary glomerular disease centers offer access to rituximab and clinical trials of newer agents.
Find specialists →Proteinuria typically begins to fall within 6-12 weeks of starting ACE inhibitor or ARB, and within 3-6 months of starting immunosuppression. Complete remission (proteinuria under 0.3 g/day) usually takes 12-24 months on rituximab and 6-12 months on cyclophosphamide-based regimens. Anti-PLA2R titers fall before proteinuria, often within 3-6 months of effective therapy. Edema resolves within weeks of diuretic and protein response. Sustained remission after rituximab can last several years; re-treatment is timed by titer rebound and proteinuria recurrence.
Moderate aerobic activity is safe and beneficial once severe edema is controlled. Patients on anticoagulation should avoid contact sports. Resistance training supports lean mass during steroid therapy. Restart progressively after rituximab infusions and check for any new infection or flare before increasing intensity.
Choose a nephrologist with experience in glomerular diseases — KDIGO-aligned protocols, access to anti-PLA2R testing, and a working relationship with renal pathology, oncology, and hepatology. Tertiary centers with dedicated glomerular disease clinics or trial enrolment are preferred for high-risk or refractory disease.
Medically reviewed by AIHealz Medical Editorial Board · May 13, 2026
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