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Membranous nephropathy

Guidelines

Key sources

The following summarized guidelines for the evaluation and management of membranous nephropathy are prepared by our editorial team based on guidelines from the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2021)....
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Classification and risk stratification

Prognosis: as per KDIGO 2021 guidelines, Use clinical and laboratory criteria to assess the risk of progressive loss of kidney function in patients with membranous nephropathy:
Situation
Guidance
Low risk
Normal eGFR, proteinuria < 3.5 g/day, and serum albumin > 30 g/L
Normal eGFR, proteinuria < 3.5 g/day or a decrease > 50% after 6 months of conservative therapy with ACEI/ARB
Moderate risk
Normal eGFR, proteinuria > 3.5 g/day and no decrease > 50% after 6 months of conservative therapy with ACEI/ARB, and not meeting high-risk criteria
High risk
EGFR < 60 mL/min/1.73 m² and/or proteinuria > 8 g/day for > 6 months
Normal eGFR, proteinuria > 3.5 g/day and no decrease > 50% after 6 months of conservative therapy with ACEI/ARB, and at least one of the following
Very high risk
Life-threatening nephrotic syndrome or rapid deterioration of kidney function not otherwise explained
E
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Diagnostic investigations

Evaluation for secondary causes: as per KDIGO 2021 guidelines, Evaluate patients with membranous nephropathy for associated conditions obtaining the following, regardless of whether anti-PLA2R and/or anti-THSD7A antibodies are present or absent:
full medical history (including systemic diseases, thyroid disease), history of medication use (NSAIDs, gold, penicillamine), and physical examination (skin, joints)
screening for malignancies (population and age-appropriate)
kidney ultrasound
CXR (sarcoidosis)
ANA
HBV, HCV, HIV, and treponemal infection (on indication).
E

Diagnostic procedures

Kidney biopsy: as per KDIGO 2021 guidelines, Do not perform kidney biopsy to confirm the diagnosis of membranous nephropathy in patients with nephrotic syndrome and a positive anti-PLA2R antibody test.
D

Medical management

General principles
As per KDIGO 2021 guidelines:
Provide optimal supportive care in all patients with primary membranous nephropathy and proteinuria.
E
Decide on the treatment strategy based on the risk evaluation:
Situation
Guidance
Low risk
Observation
Moderate risk
Observation, or rituximab, or calcineurin inhibitor with or without corticosteroids
High risk
Rituximab, or cyclophosphamide with corticosteroids, or calcineurin inhibitors with rituximab
Very high risk
Cyclophosphamide with corticosteroids
E

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Surgical interventions

Kidney transplantation
As per KDIGO 2021 guidelines:
Obtain pretransplant evaluation in patients with membranous nephropathy to ascertain if membranous nephropathy is associated with PLA2Rab. Measure PLA2Rab in patients with known or unknown PLA2Rab-associated membranous nephropathy.
E
Classify patients into the following categories for risk of recurrence:
Situation
Guidance
High risk (50%)
Positive PLA2Rab
Medium risk (30%)
Negative PLA2Rab and negative native kidney biopsy and stain for PLA2R antigen
Low risk (10%)
Negative PLA2Rab and positive native kidney biopsy and stain for PLA2R antigen (antibodies have disappeared)
E

Specific circumstances

Pediatric patients: as per KDIGO 2021 guidelines, Perform kidney biopsy in pediatric patients with membranous nephropathy.
E
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Follow-up and surveillance

Serial laboratory assessment: as per KDIGO 2021 guidelines, Consider monitoring the anti-PLA2R antibody levels after 6 months of treatment initiation to evaluate treatment response in patients with membranous nephropathy and to guide adjustments to therapy.
E
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