Top

International Urology and Nephrology

Published in:

24-03-2023 | Biomarkers | Nephrology - Review

Diagnostic utility of serum and urine biomarkers in idiopathic membranous nephropathy: a systematic review and meta-analysis

Authors: Dan Gao, Li-Ping Lu, Zhi-Guo Zhao

Published in: International Urology and Nephrology | Issue 10/2023

Abstract

Background

Membranous nephropathy is an autoimmune nephropathy that is one of the most common pathological types of nephrotic syndrome. It is important to find and apply specific biomarkers for the noninvasive diagnosis of idiopathic membranous nephropathy (IMN). However, there are limited data about their diagnostic value. Therefore, an overall meta-analysis helps to identify effective biomarkers for the clinical diagnosis of IMN.

Methods

A systematic literature search was carried out in PubMed, Embase, Cochrane and Web of Science from inception until December 31, 2020. Two researchers searched for studies that met the inclusion criteria. The results of the joint study were expressed in terms of sensitivity and specificity.

Results

The meta-analysis included 24 studies with biomarkers for the clinical diagnosis of IMN, including antibody against phospholipase A2 receptor (PLA₂R-AB), antibody against thrombospondin type I domain-containing 7A (THSD7A-AB), lysosome membrane protein-2 (LIMP-2) and circular RNAs. The diagnostic efficiency of PLA₂R-AB for IMN had a combined sensitivity of 60% and a combined specificity of 100%. The diagnostic efficiency of THSD7A-AB for IMN had a combined sensitivity of 3% and a combined specificity of 99%. The diagnostic efficiency of urinary LIMP-2 for IMN was 100%, and the specificity was 100%. The diagnostic efficiency of exosomal circRNAs for IMN was 100%, and the specificity was 100%.

Conclusions

This meta-analysis shows that PLA₂R-AB and THSD7A-AB are of important diagnostic value for IMN. More studies are needed in the future to reveal the diagnostic value of LIMP-2 and circRNAs for IMN.

Bobkova IN, Kamyshova ES (2020) Modern view on treatment of membranous nephropathy. Ter Arkh 92:99–104. https://doi.org/10.26442/00403660.2020.06.000676CrossRefPubMed

Sim JJ, Bhandari SK, Batech M et al (2018) End-stage renal disease and mortality outcomes across different glomerulonephropathies in a large diverse US population. Mayo Clin Proc 93:167–178. https://doi.org/10.1016/j.mayocp.2017.10.021CrossRefPubMed

Rozenberg I, Kotliroff A, Zahavi T et al (2018) Outcome of idiopathic membranous nephropathy: a retrospective study. Isr Med Assoc J 20:186–189PubMed

Lai WL, Yeh TH, Chen PM et al (2015) Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment. J Formos Med Assoc 114:102–11. https://doi.org/10.1016/j.jfma.2014.11.002CrossRefPubMed

Xu X, Wang G, Chen N et al (2016) Long-term exposure to air pollution and increased risk of membranous nephropathy in China. J Am Soc Nephrol 27:3739–3746. https://doi.org/10.1681/ASN.2016010093CrossRefPubMedPubMedCentral

Tang L, Yao J, Kong X et al (2017) Increasing prevalence of membranous nephropathy in patients with primary glomerular diseases: a cross sectional study in China. Nephrology (Carlton) 22:168–173. https://doi.org/10.1111/nep.12739CrossRefPubMed

Liu Y, Zheng S, Ma C et al (2020) Meta-analysis of the diagnostic efficiency of THSD7A-AB for the diagnosis of idiopathic membranous nephropathy. Glob Chall 4:1900099. https://doi.org/10.1002/gch2.201900099CrossRefPubMedPubMedCentral

Wu X, Wen S, Zhu X et al (2017) Diagnostic value of renal phospholipase A2 receptor and serum anti-phospholipase A2 receptor antibody in membranous nephropathy. Zhong nan da xue xue bao Yi xue ban 42:395–399. https://doi.org/10.11817/j.issn.1672-7347.2017.04.005CrossRefPubMed

Liu L, Chang B, Wu X et al (2018) Expression of phospholipase A2 receptor and IgG4 in patients with membranous nephropathy. Vasc Health Risk Manag 14:103–108. https://doi.org/10.2147/VHRM.S160883CrossRefPubMedPubMedCentral

10.

Rood IM, Merchant ML, Wilkey DW et al (2015) Increased expression of lysosome membrane protein 2 in glomeruli of patients with idiopathic membranous nephropathy. Proteomics 15:3722–3730. https://doi.org/10.1002/pmic.201500127CrossRefPubMed

11.

Ma H, Xu Y, Zhang R et al (2019) Differential expression study of circular RNAs in exosomes from serum and urine in patients with idiopathic membranous nephropathy. Arch Med Sci 15:738–753. https://doi.org/10.5114/aoms.2019.84690CrossRefPubMedPubMedCentral

12.

Whiting PF, Rutjes AW, Westwood ME et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155:529–536. https://doi.org/10.7326/0003-4819-155-8-201110180-00009CrossRefPubMed

13.

Xu M, Rui D, Yan Y et al (2017) Oxidative damage induced by arsenic in mice or rats: a systematic review and meta-analysis. Biol Trace Elem Res 176:154–175. https://doi.org/10.1007/s12011-016-0810-4CrossRefPubMed

14.

Crippa A, Orsini N (2016) Dose-response meta-analysis of differences in means. BMC Med Res Methodol 16:91. https://doi.org/10.1186/s12874-016-0189-0CrossRefPubMedPubMedCentral

15.

Beck LH Jr, Bonegio RG, Lambeau G et al (2009) M-type phospholipase A₂ receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 361:11–21. https://doi.org/10.1056/NEJMoa0810457CrossRefPubMedPubMedCentral

16.

Hoxha E, Harendza S, Zahner G et al (2011) An immunofluorescence test for phospholipase-A₂-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis. Nephrol Dial Transplant 26:2526–2532. https://doi.org/10.1093/ndt/gfr247CrossRefPubMed

17.

Murtas C, Bruschi M, Candiano G et al (2012) Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy. Clin J Am Soc Nephrol 7:1394–1400. https://doi.org/10.2215/CJN.02170312CrossRefPubMedPubMedCentral

18.

Behnert A, Fritzler MJ, Teng B et al (2013) An anti-phospholipase A₂ receptor quantitative immunoassay and epitope analysis in membranous nephropathy reveals different antigenic domains of the receptor. PLoS One 8:e61669. https://doi.org/10.1371/journal.pone.0061669CrossRefPubMedPubMedCentral

19.

Tomas NM, Beck LH Jr, Meyer-Schwesinger C et al (2014) Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 371:2277–2287. https://doi.org/10.1056/NEJMoa1409354CrossRefPubMedPubMedCentral

20.

Kim YG, Choi YW, Kim SY et al (2015) Anti-phospholipase A2 receptor antibody as prognostic indicator in idiopathic membranous nephropathy. Am J Nephrol 42:250–257. https://doi.org/10.1159/000440983CrossRefPubMed

21.

Yang X, Pan Y, Ding G (2015) Correlation of secreted phospholipase A2-I B, anti-phospholipase A2 receptor antibody with idiopathic membranous nephropathy among adult patients. Chinese General Practice 18:1018–1022, 1028. https://doi.org/10.3969/j.issn.1007-9572.2015.09.009CrossRef

22.

Li X, Wei D, Zhou Z et al (2016) Anti-PLA₂R antibodies in Chinese patients with membranous nephropathy. Med Sci Monit 22:1630–6. https://doi.org/10.12659/msm.896090CrossRefPubMedPubMedCentral

23.

Wang J, Cui Z, Lu J et al (2017) Circulating antibodies against thrombospondin type-I domain-containing 7A in Chinese patients with idiopathic membranous nephropathy. Clin J Am Soc Nephrol 12:1642–1651. https://doi.org/10.2215/CJN.01460217CrossRefPubMedPubMedCentral

24.

Zhang Q, Huang B, Liu X et al (2017) Ultrasensitive quantitation of anti-phospholipase A2 receptor antibody as a diagnostic and prognostic indicator of idiopathic membranous nephropathy. Sci Rep 7:12049. https://doi.org/10.1038/s41598-017-12014-1CrossRefPubMedPubMedCentral

25.

Radice A, Pieruzzi F, Trezzi B et al (2018) Diagnostic specificity of autoantibodies to M-type phospholipase A₂ receptor (PLA₂R) in differentiating idiopathic membranous nephropathy (IMN) from secondary forms and other glomerular diseases. J Nephrol 31:271–278. https://doi.org/10.1007/s40620-017-0451-5CrossRefPubMed

26.

Cheng G, Liu J, Gilbert A et al (2019) Serum phospholipase A2 receptor antibodies and immunoglobulin G subtypes in adult idiopathic membranous nephropathy: clinical value assessment. Clin Chim Acta 490:135–141. https://doi.org/10.1016/j.cca.2018.12.027CrossRefPubMed

27.

Zaghrini C, Seitz-Polski B, Justino J et al (2019) Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy. Kidney Int 95:666–679. https://doi.org/10.1016/j.kint.2018.10.024CrossRefPubMed

28.

Zhenzhen H, Yuan F, Wei C (2020) Effects of the expression of serum PLA2R antibody on the diagnosis and immunological therapy of idiopathic membranous nephropathy. Int J Clin Exp Med 13:5959–5966

29.

Maifata SM, Hod R, Zakaria F et al (2020) Role of serum and urine biomarkers (PLA₂R and THSD7A) in diagnosis, monitoring and prognostication of primary membranous glomerulonephritis. Biomolecules 10:319. https://doi.org/10.3390/biom10020319CrossRefPubMedPubMedCentral

30.

Hu SL, Wang D, Gou WJ et al (2014) Diagnostic value of phospholipase A2 receptor in idiopathic membranous nephropathy: a systematic review and meta-analysis. J Nephrol 27:111–116. https://doi.org/10.1007/s40620-014-0042-7CrossRefPubMed

31.

Burbelo PD, Joshi M, Chaturvedi A et al (2020) Detection of PLA2R autoantibodies before the diagnosis of membranous nephropathy. J Am Soc Nephrol 31:208–217. https://doi.org/10.1681/ASN.2019050538CrossRefPubMed

32.

Ren S, Wu C, Zhang Y et al (2018) An update on clinical significance of use of THSD7A in diagnosing idiopathic membranous nephropathy: a systematic review and meta-analysis of THSD7A in IMN. Ren Fail 40:306–313. https://doi.org/10.1080/0886022X.2018.1456457CrossRefPubMedPubMedCentral

Title: Diagnostic utility of serum and urine biomarkers in idiopathic membranous nephropathy: a systematic review and meta-analysis
Authors: Dan Gao
Li-Ping Lu
Zhi-Guo Zhao
Publication date: 24-03-2023
Publisher: Springer Netherlands
Keyword: Biomarkers
Published in: International Urology and Nephrology / Issue 10/2023
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI: https://doi.org/10.1007/s11255-023-03561-w

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 10/2023

Development of a novel mesh model to define a new index “amount of stone” to evaluate calculus and predicting the lithotripsy time

Sanjin Paishi Decoction improves the imbalance of gut microbiota and regulates MAPK signaling pathway to inhibit calcium oxalate stones in rats

Comparison of focal segmental glomerulosclerosis and other primary glomerulonephrites in terms of parameters of hepatic steatosis and metabolic syndrome

Does renal failure worsen radiation cystitis following radical prostatectomy?

Surgical versus interventional coronary revascularization in kidney transplant recipients: a systematic review and meta-analysis

Reno-protective effects of perioperative dexmedetomidine in kidney transplantation: a systematic review and meta-analysis of randomized controlled trials

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials