Primary Membranous Nephropathy - Idiopathic Membranous Glomerulonephritis

Membranous nephropathy (MN) is one of the common causes of nephrotic-range proteinuria. Affected patients present with peripheral edema, decreased serum albumin, and often hyperlipidemia (Kodner, 2016). Secondary causes of MN include drugs, autoimmune disease, infections, and malignancy (Kidney Disease: Improving Global Outcomes [KDIGO], 2012). Once these are ruled out, the remaining cases (approximately 75%) are considered primary or idiopathic. Renal biopsy is the gold standard for diagnosis of membranous nephropathy. Testing for phospholipase A2 receptor (PLA2R) antibody can assist with the differentiation of primary and secondary membranous nephropathy.


Indications for Testing

  • Evaluate nephrotic syndrome
  • Differentiate between primary and secondary MN

Laboratory Testing

  • Initial testing for nephrotic syndrome
    • 24-hour urine protein
    • Serum albumin
    • Testing to rule out the most common secondary disorders associated with MN
      • Antinuclear antibodies (ANAs), hepatitis B and C serologies, diabetes mellitus
      • Also consider age-appropriate cancer screening
  • If renal biopsy reveals MN or patient cannot undergo biopsy and no other obvious etiology is present
    • Serum PLA2R antibody IgG with titers
      • Relatively high specificity for primary MN (80-90%)
        • Etiologies for false positives – most commonly hepatitis B or C, autoimmune disease, or cancer


​Positive staining for PLA2R and immunoglobulin G4 (IgG4) – suggests primary MN

Differential Diagnosis


  • Serum PLA2R antibody titers can be used to assess disease activity or monitor therapy (Hofstra, 2012)
    • Decreasing titer suggests therapeutic response
    • Persistently high titer is associated with less favorable course



  • Incidence – ~1/100,000 (Bockenhauer, 2008)
    • Most common diagnosis in nondiabetic adults with nephrotic syndrome
  • Sex – M>F
  • Age – most commonly, 40-70 years


Familial occurrence associated with HLA-DQA1 (Stanescu, 2011)


  • Autoimmune disorder – several antibodies identified in MN
    • M-type PLA2R antibody
      • Found in majority (≥70%) of patients with primary MN; not found in secondary MN
      • Predominantly IgG4 antibodies
    • Thrombospondin type-1 domain-containing 7A (THSD7A) antibody
      • Predominantly IgG4 antibodies
      • Mutually exclusive for PLA2R antibody
      • Detected in 8-14% of patients with MN (Tomas, 2014)
    • Neutral endopeptidase (NEP) antibody 
      • Found in alloimmune antenatal MN (Debiec, 2002)
      • Predominantly IgG1 antibodies in neonates
  • Antibodies cause formation of  immune complexes that are deposited in basement membrane of glomeruli
    • Immune complexes activate complement to form membrane attack complexes that damage renal epithelial cells, leading to nephrotic syndrome
    • Antibodies mirror disease activity

Clinical Presentation

  • Asymptomatic proteinuria
    • Found in small percentage of patients presenting with primary MN
    • Usually discovered on urine dipstick testing for other disorders such as urinary tract infection
  • Nephrotic syndrome
    • Found in majority of patients presenting with primary MN
    • Clinical hallmark is edema (lower extremities and face most common sites)
      • Weight gain
      • Usually no heart or liver failure
      • Hypertension may occur, but majority are normotensive
    • Laboratory-hypoalbuminemia, proteinuria (>3.5 gm/day), hyperlipidemia
      • May have hematuria
      • Serum creatinine –  typically normal or near normal at presentation
  • End-stage renal disease – common in untreated primary MN

ARUP Laboratory Tests

Aid in confirmation of nephrotic syndrome

May assist in assessing nutritional status or in indicating a possible chronic process

Differentiate between primary and secondary MN

Monitor therapy efficacy and disease status

Negative result does not rule out the diagnosis of primary MN

Results should be used in conjunction with other laboratory tests and clinical findings

Reflex pattern: if PLA2R antibody, IgG is positive, then a PLA2R antibody, IgG titer is reported

Related Tests

Aid in initial diagnosis of connective tissue disease

Positive nuclear patterns reported include homogeneous, speckled, centromere, nucleolar, or nuclear dots; positive cytoplasmic patterns reported include reticular/AMA, discrete/GW body-like, polar/golgi-like, rods and rings, or cytoplasmic speckled patterns

Reflex pattern: if ANA are detected by ELISA, then ANA, HEp-2, IgG by IFA will be added

Can be ordered as part of the acute hepatitis panel, which includes hepatitis A virus (HAV) IgM, hepatitis B virus (HBV) core antibody IgM, HBV surface antigen (HBsAg), and hepatitis C virus (HCV) antibody; refer to acute hepatitis panel with reflex to HBsAg confirmation

Reflex pattern: if results for HBsAg screen are repeatedly reactive with an index value between 1.00 and 50.00, then HBsAg confirmation will be added

Preferred single screening test for individuals at risk for HCV infection

One-time screening for population born between 1945 and 1965

Positive results require confirmation by molecular testing using quantitative polymerase chain reaction (PCR)

Medical Experts



Additional Resources