Mayo Clinic Laboratories > Renal > Glomerular disease > Membranous nephropathy

MEmbranous nePHropathy

Classify subtype, guide therapy, and monitor responses

Membranous nephropathy (MN) is one of the leading causes of nephrotic syndrome in adults. It is traditionally classified into primary and secondary membranous nephropathy. Cases without associated disorders are termed primary membranous nephropathy (PMN) while cases associated with other conditions, such as different autoimmune diseases, infectious or parasitic diseases, tumor, or adverse reactions to certain medications, are referred to as secondary membranous nephropathy (SMN).

As more antigens that autoantibodies recognize are identified, the distinction between PMN and SMN is becoming blurred. While certain target antigens are more strongly associated with specific secondary causes,1 other autoantibodies associated with the same antigen can be associated with both types. The variable and unpredictable natural course of MN and other associated diseases results in ongoing challenges for disease management.2

70%

70% of patients with primary MN are positive for PLA2R

2%-5%

2%–5% of patients with primary MN are positive for NELL-1

1%

1% of patients with primary MN are positive for THSD7A

Membranous nePHropathy test menu

Primary membranous nephropathy Primary membranous nephropathy
Additional testing Additional testing

Primary membranous nephropathy

Mayo Clinic Laboratories offers a comprehensive menu of clinically validated assays to assist with the diagnosis of PMN, monitor disease progression, and guide clinical outcomes.

Key testing

Advantages

  • Detects low levels of anti-PLA2R antibodies in patients with borderline or negative PLA2R ELISA results.
  • Distinguishes PLA2R-associated MN from THSD7-associated MN in patients with biopsy-proven MN.
  • Determines levels of anti-PLA2R antibodies to predict remission or disease relapse status.
  • Determines relapse or presence of untreated disease in chronic kidney disease patients awaiting a transplant.
  • Provides an alternative diagnostic option for some patients who cannot undergo a kidney biopsy due to contraindications.
    • New KDIGO guidelines suggest a PMN diagnosis can be confirmed for PLA2R via ELISA or IFA if the eGFR is >60 and SMN causes are nonexistent.
Algorithm View the PMND1 cascade
Learn more Membranous nephropathy classification

Highlights

Membranous nephropathy assay: PMND1

John Lieske, M.D., describes Mayo Clinic Laboratories' new test for primary membranous nephropathy. PMND1 is a diagnostic cascade that provides a cost-effective approach to detecting antigens known to cause membranous nephropathy — a condition that can lead to kidney failure.

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Additional testing

Mayo Clinic Laboratories offers a comprehensive menu of ancillary renal pathology tests to assist with the diagnosis of membranous nephropathy.

Highlights

Testing for a surprising antigen enables insight into a chronic kidney illness

Mayo Clinic renal pathologist Dr. Sanjeev Sethi identified NELL-1 as a biomarker for membranous nephropathy (MN) in 2019. Two years later, Dr. Sethi helped implement the first ever IHC test to detect NELL-1 antigen, which appears in about 10% of MN patients and is linked to underlying malignancy.

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NELL-1 [Test in Focus]

Sanjeev Sethi, M.D., Ph.D., discusses how Mayo Clinic Laboratories’ new immunohistochemistry test for the detection of NELL-1 antigen, a biomarker for membranous nephropathy found in 10% to 15% of patients, provides diagnostic certainty and insight on disease expression.

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References
  1. Sethi S. New ‘antigens’ in membranous nephropathy. J Am Soc Nephrol. 2021 Feb;32(2):268-278. doi:10.1681/ASN.2020071082. Epub 2020 Dec 30. PMID: 33380523; PMCID: PMC8054892.
  2. Dahan K, Gillion V, Johanet C, Debiec H, Ronco P. The role of PLA2R antibody in treatment of membranous nephropathy. Kidney Int Rep. 2017 Nov 3;3(2):498-501. doi:10.1016/j.ekir.2017.10.013. PMID: 29725656; PMCID: PMC5932125.
  3. Beck LH Jr, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009 Jul 2;361(1):11-21. doi:10.1056/NEJMoa0810457. PMID: 19571279; PMCID: PMC2762083.
  4. Tomas NM, Beck LH Jr, Meyer-Schwesinger C, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 2014 Dec 11;371(24):2277-2287. doi:10.1056/NEJMoa1409354. Epub 2014 Nov 13. PMID: 25394321; PMCID: PMC4278759.
  5. Sethi S, Debiec H, Madden B, et al. Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy. Kidney Int. 2020 Jan;97(1):163-174. doi:10.1016/j.kint.2019.09.014. Epub 2019 Oct 7. PMID: 31901340.
  6. Sethi S, Madden BJ, Debiec H, et al. Exostosin 1/exostosin 2-associated membranous nephropathy. J Am Soc Nephrol. 2019 Jun;30(6):1123-1136. doi:10.1681/ASN.2018080852. Epub 2019 May 6. PMID: 31061139; PMCID: PMC6551791.
  7. Sethi S, Debiec H, Madden B, et al. Semaphorin 3B-associated membranous nephropathy is a distinct type of disease predominantly present in pediatric patients. Kidney Int. 2020 Nov;98(5):1253-1264. doi:10.1016/j.kint.2020.05.030. Epub 2020 Jun 11. PMID: 32534052.
  8. Sethi S, Madden B, Debiec H, et al. Protocadherin 7-associated membranous nephropathy. J Am Soc Nephrol. 2021 May 3;32(5):1249-1261. doi:10.1681/ASN.2020081165. Epub 2021 Apr 8. PMID: 33833079; PMCID: PMC8259689.
  9. Sethi S, Madden B, Casal Moura M, et al. Hematopoietic stem cell transplant-membranous nephropathy is associated with protocadherin FAT1. J Am Soc Nephrol. 2022 Mar 23:ASN.2021111488. doi:10.1681/ASN.2021111488. Epub ahead of print. PMID: 35321939.
  10. Bobart S, Tehranian S, Sethi S, et al. A target antigen-based approach to the classification of membranous nephropathy. Mayo Clin Proc. 2021;96(3):577-591, ISSN 0025-6196, https://doi.org/10.1016/j.mayocp.2020.11.028.
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