October 2023
Ampath | ampath.co.za
Overview
Membranous nephropathy (MN) is characterised by thickening of the glomerular capillary walls due to the formation of immune complexes on the outer basement membrane.
- MN is the most common cause of nephrotic syndrome in non-diabetic adults.
- Around 20% of MN cases are linked to secondary causes such as:
- Autoimmune disease
- Hepatitis B or C
- Thyroiditis
- Malignancy
- Medications (e.g. NSAIDs)
- The remaining 80% of cases are classified as primary membranous nephropathy (PMN), where no underlying cause is found.
The Role of Anti-PLA₂R Antibodies:
- Up to 80% of PMN patients have auto-antibodies against phospholipase A2 receptor (PLA₂R), a podocyte antigen.
- These antibodies are highly specific for PMN.
- Their binding leads to podocyte injury and impaired filtration function.
Who Should Be Tested?
Diagnosis of MN should be considered in any adult patient presenting with signs of nephrotic syndrome, such as:
- Significant proteinuria
- Hypoalbuminemia
- Oedema
- Unexplained weight gain
Diagnostic Approach for Suspected MN
In line with KDIGO 2021 guidelines, a non-invasive diagnostic approach is preferred for adults with suspected PMN. This includes:
✅ Clinical History and Screening for Secondary Causes:
- Infections (HIV, Hepatitis B, Hepatitis C)
- Autoimmune diseases
- Cancer
- Medication review
- Diabetes mellitus (rule out diabetic nephropathy)
✅ Laboratory Investigations:
- Serum albumin
- Full blood count
- Urinalysis
- 24-hour urine protein
- ANA and ds-DNA
- ENA/CTD screen
- Complement levels (C3, C4)
- Serum-free light chain and protein electrophoresis (especially if >50 years)
- Chest X-ray (optional, for malignancy screening)
- Anti-PLA₂R antibody test
If anti-PLA₂R antibodies are positive and secondary causes are excluded, a renal biopsy may not be required to confirm the diagnosis of PLA₂R-associated PMN.
Monitoring and Risk Stratification Using Anti-PLA₂R Antibodies
Anti-PLA₂R antibody titres can be monitored to guide treatment decisions:
✅ How Often?
- Every 3 to 6 months, depending on clinical scenario
✅ Interpretation of Trends:
- High or unchanged titres: Indicates high risk of disease progression
- Low or decreasing titres: Suggests treatment response or lower risk
- Negative titres: May support tapering or stopping treatment
Risk Categories for Disease Progression
Risk is determined based on anti-PLA₂R antibody titres, kidney function (eGFR), and proteinuria:
🔹 Low Risk
- Normal/stable eGFR
- Proteinuria <4 g/day
- Low antibody titres
- Management: Observation or conservative management
🔹 Moderate Risk
- Normal/stable eGFR
- Proteinuria 4–8 g/day
- Stable or moderate antibody titres
- Management: Consider RTX, CNI ± glucocorticoids
🔹 High Risk
- Proteinuria >8 g/day after observation
- High, stable anti-PLA₂R titres
- Management: Escalation of immunosuppressive therapy (e.g., RTX, CP)
🔹 Very High Risk
- Rapid decline in eGFR or life-threatening nephrotic syndrome
- eGFR drop >25% from baseline
- Management: Aggressive treatment (e.g., CP + glucocorticoids)
Monitoring During Treatment
- Anti-PLA₂R titres reflect immunological response
- Should be considered alongside:
- 24-hour proteinuria
- Serum albumin
- Serum creatinine
- Testing is also recommended prior to kidney transplantation due to risk of disease recurrence associated with high titres.
Test Details
- Test name: Anti-PLA₂R Antibodies
- Method: Transfected cell-based indirect immunofluorescence (IIFT)
- Specimen: Serum (SST tube)
- Mnemonic:
PLA2R - Turnaround time: 48 hours (weekdays only)
- Test characteristics:
- High sensitivity and specificity for PMN
- Cost-effective
- No batching required → faster reporting
📌 For more info or guidance, contact your local Ampath nephrologist or pathologist.