Membranous nephropathy: the current state of the problem

Authors

  • O.N. Sharapov Republican Specialized Scientific Practical Medical Center of Nephrology and Kidney Transplantation, Tashkent, Uzbekistan; Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan
  • Sh.S. Abdullaev Republican Specialized Scientific Practical Medical Center of Nephrology and Kidney Transplantation, Tashkent, Uzbekistan; Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan

DOI:

https://doi.org/10.22141/2307-1257.12.2.2023.406

Keywords:

membranous nephropathy, nephrotic syndrome, basement membrane of the glomerulus, proteinuria, antibodies, PLA2R, THSD7A, review

Abstract

Membranous nephropathy (MN) is an autoimmune disease of the kidney glomeruli and one of the leading causes of nephrotic syndrome. The disease exhibits heterogenous outcomes with approximately 30 % of cases progressing to end-stage renal disease. The study of MN pathogenesis has steadily advanced owing to the identification of autoantibodies to the phospholipase A2 receptor (PLA2R) in 2009 and thrombospondin domain-containing 7A (THSD7A) on the podocyte surface in 2014. Approximately 50–80 and 3–5 % of primary MN cases are associated with either anti-PLA2R or anti-THSD7A antibodies, respectively. The presence of these autoantibodies is used for MN diagnosis; antibody levels correlate with disease severity and possess significant biomarker values in monitoring disease progression and treatment response.

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References

Ronco P, Debiec H. Molecular Pathogenesis of Membranous Nephropathy. Annu Rev Pathol. 2020 Jan 24;15:287-313. doi:10.1146/annurev-pathol-020117-043811.

Alsharhan L, Beck LH Jr. Membranous Nephropathy: Core Curriculum 2021. Am J Kidney Dis. 2021 Mar;77(3):440-453. doi:10.1053/j.ajkd.2020.10.009.

Johnson RJ, Feehally J, Floege J, Tonelli M, editors. Comprehensive Clinical Nephrology. 6th ed. Edinburgh: Elsevier; 2019. 1360 p.

Özer H, Baloğlu I, Fervenza FC, Türkmen K. Membranous nephropathy: current understanding in the light of new advances. Turk J Nephrol. 2023;32(2):103-111. doi:10.5152/turkjnephrol.2023.22123421.

Ozturk S, Sumnu A, Seyahi N, et al. Demographic and clinical characteristics of primary glomerular diseases in Turkey. Int Urol Nephrol. 2014 Dec;46(12):2347-2355. doi:10.1007/s11255-014-0838-3.

United States Renal Data System (USRDS). 2018 USRDS Annual Data Report: Epidemiology of kidney disease in the United States. Bethesda, MD: NIDDKD; 2018. Available from: https://www.niddk.nih.gov/about-niddk/strategic-plans-reports/usrds/prior-data-reports/2018.

Ayalon R, Beck LH Jr. Membranous nephropathy: not just a disease for adults. Pediatr Nephrol. 2015 Jan;30(1):31-39. doi:10.1007/s00467-013-2717-z.

Hofstra JM, Wetzels JF. Introduction of a cyclophosphamide-based treatment strategy and the risk of ESRD in patients with idiopathic membranous nephropathy: a nationwide survey in the Netherlands. Nephrol Dial Transplant. 2008 Nov;23(11):3534-3538. doi:10.1093/ndt/gfn350.

Li LS, Liu ZH. Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies. Kidney Int. 2004 Sep;66(3):920-923. doi:10.1111/j.1523-1755.2004.00837.x.

Dobronravov VA, Mayer DA, Berezhnaya OV, et al. Membranous nephropathy in a Russian population. Ter Arkh. 2017;89(6):21-29. doi:10.17116/terarkh201789621-29. (in Russian).

Hu R, Quan S, Wang Y, et al. Spectrum of biopsy proven renal diseases in Central China: a 10-year retrospective study based on 34,630 cases. Sci Rep. 2020 Jul 3;10(1):10994. doi:10.1038/s41598-020-67910-w.

Couser WG. Primary Membranous Nephropathy. Clin J Am Soc Nephrol. 2017 Jun 7;12(6):983-997. doi:10.2215/CJN.11761116.

Heymann W, Hackel DB, Harwood S, Wilson SG, Hunter JL. Production of nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspensions. Proc Soc Exp Biol Med. 1959 Apr;100(4):660-664. doi:10.3181/00379727-100-24736.

Kerjaschki D, Farquhar MG. The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. Proc Natl Acad Sci USA. 1982 Sep;79(18):5557-5561. doi:10.1073/pnas.79.18.5557.

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.

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.

Du Y, Li J, He F, et al. The diagnosis accuracy of PLA2R-AB in the diagnosis of idiopathic membranous nephropathy: a meta-analysis. PLoS One. 2014 Aug 19;9(8):e104936. doi:10.1371/journal.pone.0104936.

Akiyama S, Akiyama M, Imai E, Ozaki T, Matsuo S, Maruyama S. Prevalence of anti-phospholipase A2 receptor antibodies in Japanese patients with membranous nephropathy. Clin Exp Nephrol. 2015 Aug;19(4):653-660. doi:10.1007/s10157-014-1054-2.

Hofstra JM, Wetzels JF. Anti-PLA₂R antibodies in membranous nephropathy: ready for routine clinical practice? Neth J Med. 2012 Apr;70(3):109-113.

Iwakura T, Ohashi N, Kato A, Baba S, Yasuda H. Prevalence of Enhanced Granular Expression of Thrombospondin Type-1 Domain-Containing 7A in the Glomeruli of Japanese Patients with Idiopathic Membranous Nephropathy. PLoS One. 2015 Sep 22;10(9):e0138841. doi:10.1371/journal.pone.0138841.

Akiyama S, Imai E, Maruyama S. Immunology of membranous nephropathy. F1000Res. 2019 May 24;8:F1000 Faculty Rev-734. doi:10.12688/f1000research.17589.1.

Yamaguchi M, Ando M, Yamamoto R, et al. Patient age and the prognosis of idiopathic membranous nephropathy. PLoS One. 2014 Oct 20;9(10):e110376. doi:10.1371/journal.pone.0110376.

Wang Y, Wang GP, Li BM, Chen QK. Clinicopathological analysis of idiopathic membranous nephropathy in young adults. Genet Mol Res. 2015 May 4;14(2):4541-4548. doi:10.4238/2015.May.4.12.

Xu Z, Chen L, Xiang H, Zhang C, Xiong J. Advances in Pathogenesis of Idiopathic Membranous Nephropathy. Kidney Dis (Basel). 2020 Sep;6(5):330-345. doi:10.1159/000507704.

Xian L, Dong D, Luo J, et al. Expression of THSD7A in neoplasm tissues and its relationship with proteinuria. BMC Nephrol. 2019 Aug 23;20(1):332. doi:10.1186/s12882-019-1489-5.

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.

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.

Hayashi N, Beck LH Jr. Moore's law for membranous nephropathy. Kidney Int. 2020 Nov;98(5):1081-1084. doi:10.1016/j.kint.2020.06.020.

Caza TN, Hassen SI, Kuperman M, et al. Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis. Kidney Int. 2021 Jul;100(1):171-181. doi:10.1016/j.kint.2020.09.016.

Ahmad SB, Appel GB. Antigens, antibodies, and membranous nephropathy: a decade of progress. Kidney Int. 2020 Jan;97(1):29-31. doi:10.1016/j.kint.2019.10.009.

Stehlé T, Audard V, Ronco P, Debiec H. Phospholipase A2 receptor and sarcoidosis-associated membranous nephropathy. Nephrol Dial Transplant. 2015 Jun;30(6):1047-1050. doi:10.1093/ndt/gfv080.

Xie Q, Li Y, Xue J, et al. Renal phospholipase A2 receptor in hepatitis B virus-associated membranous nephropathy. Am J Nephrol. 2015;41(4-5):345-353. doi:10.1159/000431331.

Larsen CP, Messias NC, Silva FG, Messias E, Walker PD. Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies. Mod Pathol. 2013 May;26(5):709-715. doi:10.1038/modpathol.2012.207.

Debiec H, Guigonis V, Mougenot B, et al. Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies. N Engl J Med. 2002 Jun 27;346(26):2053-2060. doi:10.1056/NEJMoa012895.

Polanco N, Gutiérrez E, Covarsí A, et al. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol. 2010 Apr;21(4):697-704. doi:10.1681/ASN.2009080861.

Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ. Anti-phospholipase A₂ receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2011 Jun;6(6):1286-1291. doi:10.2215/CJN.07210810.

Hoxha E, Harendza S, Pinnschmidt H, Panzer U, Stahl RA. PLA2R antibody levels and clinical outcome in patients with membranous nephropathy and non-nephrotic range proteinuria under treatment with inhibitors of the renin-angiotensin system. PLoS One. 2014 Oct 14;9(10):e110681. doi:10.1371/journal.pone.0110681.

Beck LH Jr, Salant DJ. Membranous nephropathy: recent travels and new roads ahead. Kidney Int. 2010 May;77(9):765-770. doi:10.1038/ki.2010.34.

Li SJ, Guo JZ, Zuo K, et al. Thromboembolic complications in membranous nephropathy patients with nephrotic syndrome-a prospective study. Thromb Res. 2012 Sep;130(3):501-505. doi:10.1016/j.thromres.2012.04.015.

Rankin AJ, McQuarrie EP, Fox JG, Geddes CC, MacKinnon B; Scottish Renal Biopsy Registry. Venous thromboembolism in primary nephrotic syndrome - is the risk high enough to justify prophylactic anticoagulation? Nephron. 2017;135(1):39-45. doi:10.1159/000448628.

Lee T, Biddle AK, Lionaki S, et al. Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy. Kidney Int. 2014 Jun;85(6):1412-1420. doi:10.1038/ki.2013.476.

Leeaphorn N, Kue-A-Pai P, Thamcharoen N, Ungprasert P, Stokes MB, Knight EL. Prevalence of cancer in membranous nephropathy: a systematic review and meta-analysis of observational studies. Am J Nephrol. 2014;40(1):29-35. doi:10.1159/000364782.

Hoxha E, Wiech T, Stahl PR, et al. A Mechanism for Cancer-Associated Membranous Nephropathy. N Engl J Med. 2016 May 19;374(20):1995-1996. doi:10.1056/NEJMc1511702.

Timmermans SA, Ayalon R, van Paassen P, et al. Anti-phospholipase A2 receptor antibodies and malignancy in membranous nephropathy. Am J Kidney Dis. 2013 Dec;62(6):1223-1225. doi:10.1053/j.ajkd.2013.07.019.

Stahl PR, Hoxha E, Wiech T, Schröder C, Simon R, Stahl RA. THSD7A expression in human cancer. Genes Chromosomes Cancer. 2017 Apr;56(4):314-327. doi:10.1002/gcc.22440.

Cattran DC, Brenchley PE. Membranous nephropathy: integrating basic science into improved clinical management. Kidney Int. 2017 Mar;91(3):566-574. doi:10.1016/j.kint.2016.09.048.

Salant DJ, Cattran DC. Membranous nephropathy. In: Floege J, Johnson RJ, Feehally J, editors. Comprehensive Clinical Nephrology. 5th ed. Philadelphia, PA: Elsevier/Saunders; 2015. 239-251 pp.

Rovin BH, Adler SG, Barratt J, et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100(4):753-779. doi:10.1016/j.kint.2021.05.015.

Seitz-Polski B, Payré C, Ambrosetti D, et al. Prediction of membranous nephropathy recurrence after transplantation by monitoring of anti-PLA2R1 (M-type phospholipase A2 receptor) autoantibodies: a case series of 15 patients. Nephrol Dial Transplant. 2014 Dec;29(12):2334-2342. doi:10.1093/ndt/gfu252.

Kattah A, Ayalon R, Beck LH Jr, et al. Anti-phospholipase A₂ receptor antibodies in recurrent membranous nephropathy. Am J Transplant. 2015 May;15(5):1349-1359. doi:10.1111/ajt.13133.

Quintana LF, Blasco M, Seras M, et al. Antiphospholipase A2 Receptor Antibody Levels Predict the Risk of Posttransplantation Recurrence of Membranous Nephropathy. Transplantation. 2015 Aug;99(8):1709-1714. doi:10.1097/TP.0000000000000630.

Howman A, Chapman TL, Langdon MM, et al. Immunosuppression for progressive membranous nephropathy: a UK randomised controlled trial. Lancet. 2013 Mar 2;381(9868):744-751. doi:10.1016/S0140-6736(12)61566-9.

Cattran DC, Kim ED, Reich H, Hladunewich M, Kim SJ; Toronto Glomerulonephritis Registry group. Membranous Nephropathy: Quantifying Remission Duration on Outcome. J Am Soc Nephrol. 2017 Mar;28(3):995-1003. doi:10.1681/ASN.2015111262.

Troyanov S, Wall CA, Miller JA, Scholey JW, Cattran DC; Toronto Glomerulonephritis Registry Group. Idiopathic membranous nephropathy: definition and relevance of a partial remission. Kidney Int. 2004 Sep;66(3):1199-1205. doi:10.1111/j.1523-1755.2004.00873.x.

Thompson A, Cattran DC, Blank M, Nachman PH. Complete and partial remission as surrogate end points in membranous nephropathy. J Am Soc Nephrol. 2015 Dec;26(12):2930-2937. doi:10.1681/ASN.2015010091.

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Published

2023-07-11

How to Cite

Sharapov, O., & Abdullaev, S. (2023). Membranous nephropathy: the current state of the problem. KIDNEYS, 12(2), 111–118. https://doi.org/10.22141/2307-1257.12.2.2023.406

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Reviews