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Meta-Analysis of the Diagnostic Efficiency of THSD7A-AB for the Diagnosis of Idiopathic Membranous Nephropathy.

ABSTRACT: Thrombospondin type I domain-containing 7A (THSD7A), is a specific autoantigen of adult idiopathic membranous nephropathy (IMN), whose circulating antibody (THSD7A-AB) represents a promising biomarker for diagnosis of IMN. The objective of this meta-analysis is to investigate the diagnostic efficiency of THSD7A-AB for IMN. After rigorous data extraction, quality assessment, and data analysis, 10 articles (4545 patients) are included. For IMN, the summary sensitivity is 4% (2-7%), and the specificity is 99% (98-100%). The summary positive likelihood ratio (PLR) and negative likelihood ratio (NLR) are 5.40 (2.40-11.90) and 0.97 (0.95-0.99), respectively. The diagnostic odds ratio (DOR) is 6.00 (2.00-12.00). The area under the summary receiver operating characteristic curve (AUC) is 0.78 (0.74-0.81). For M-type phospholipase A2 receptor (PLA2R)-negative IMN, the summary sensitivity is 8% (6-10%), specificity is 100% (99-100%). The summary PLR and NLR are 15.80 (5.70-44.00) and 0.93 (0.91-0.95), respectively. The DOR is 17.00 (6.00-48.00). The AUC is 0.99 (0.98-1.00). THSD7A-AB has higher diagnostic value in PLA2R-negative patients than in IMN patients. These results suggest that THSD7A-AB could possibly be applied as an auxiliary non-invasive diagnostic method for PLA2R-negative IMN.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7607246 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Meta-Analysis of the Diagnostic Efficiency of THSD7A-AB for the Diagnosis of Idiopathic Membranous Nephropathy.

Liu Yipeng Y Zheng Shanshan S Ma Chaoqun C Lian Ying Y Zheng Xiaoli X Guan Peizhong P Wang Baobao B Gong Xiaojie X Gao Feng F Liang Liming L Xu Dongmei D

Global challenges (Hoboken, NJ) 20200906 11

Thrombospondin type I domain-containing 7A (THSD7A), is a specific autoantigen of adult idiopathic membranous nephropathy (IMN), whose circulating antibody (THSD7A-AB) represents a promising biomarker for diagnosis of IMN. The objective of this meta-analysis is to investigate the diagnostic efficiency of THSD7A-AB for IMN. After rigorous data extraction, quality assessment, and data analysis, 10 articles (4545 patients) are included. For IMN, the summary sensitivity is 4% (2-7%), and the specifi ...[more]

PMID: 33163223

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Project description:BackgroundIdiopathic membranous nephropathy (IMN) is a noninflammatory autoimmune glomerulonephropathy. Based on the risk stratification for disease progression, conservative nonimmunosuppressive and immunosuppressive therapy strategies have been recommended. However, there remains challenges. Therefore, novel approaches to treat IMN are needed. We evaluated the efficacy of Astragalus membranaceus (A membranaceus) combined with supportive care or immunosuppressive therapy in the treatment of moderate-high risk IMN.MethodsWe comprehensively searched PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the Database for Chinese Technical Periodicals, Wanfang Knowledge Service Platform, and SinoMed. We then performed a systematic review and cumulative meta-analysis of all randomized controlled trials assessing the two therapy methods.ResultsThe meta-analysis included 50 studies involving 3423 participants. The effect of A membranaceus combined with supportive care or immunosuppressive therapy is better than that of supportive care or immunosuppressive therapy along in regulating for improving 24 hours urinary total protein (MD = -1.05, 95% CI [-1.21, -0.89], P = .000), serum albumin (MD = 3.75, 95% CI [3.01, 4.49], P = .000), serum creatinine (MD = -6.24, 95% CI [-9.85, -2.63], P = .0007), complete remission rate (RR = 1.63, 95% CI [1.46, 1.81], P = .000), partial remission rate (RR = 1.13, 95% CI [1.05, 1.20], P = .0004).ConclusionsAdjunctive use of A membranaceus preparations combined with supportive care or immunosuppressive therapy have a promising treatment for improving complete response rate, partial response rate, serum albumin, and reducing proteinuria, serum creatinine levels compared to immunosuppressive therapy in people with MN being at moderate-high risk for disease progression. Given the inherent limitations of the included studies, future well-designed randomized controlled trials are required to confirm and update the findings of this analysis.

Project description:BackgroundIdiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit limited efficacy in achieving remission and may result in notable adverse reactions, warranting the exploration of novel therapeutic approaches for IMN treatment. Traditional Chinese medicine (TCM), which is extensively used for kidney disease management, is a promising alternative.ObjectiveThis study aimed to examine the safety and efficacy of TCM alone or in combination with Western medicine for the management of patients diagnosed with IMN.MethodsThis study employed a systematic search of English and Chinese electronic databases to identify randomized controlled trials (RCTs) that examined the application of TCM in the treatment of IMN. RCTs that met the predetermined inclusion and exclusion criteria and assessed the safety and efficacy of TCM alone or in combination with Western medicine in patients with IMN were included in the analysis. The methodological quality of the included studies was evaluated by using a risk-of-bias tool. All statistical analyses were performed using the RevMan software (version 5.4.2). The evidence was evaluated on the https://www.gradepro.org/website.ResultsThis study included 29 randomized controlled trials (RCTs) involving 1982 patients with moderate methodological quality that met the inclusion criteria. The results showed that, compared to Western medicine alone therapy, the use of TCM alone or in combination with Western medicine significantly improved total remission (TR) rate (risk ratios [RR] 1.38, 95% confidence interval [CI] 1.29-1.46, I2 = 0%, P < 0.00001), complete remission (CR) rate (RR 1.78, 95% CI 1.48-2.15, I2 = 0, P < 0.00001), partial remission (PR) rate (RR 1.27, 95% CI 1.161.40, I2 = 0%, P < 0.00001), and serum albumin (ALB) levels (MD: 4.05, 95% CI: 3.02-5.09, I2 = 91%, P < 0.00001). TCM alone or in combination with Western medicine also reduced proteinuria levels (mean difference [MD]: 1.05, 95% CI: 1.30 to -0.79, I2 = 95%, P < 0.00001), serum creatinine (SCr) levels (MD: 7.47, 95% CI: 13.70 to -1.24, I2 = 97%, P = 0.02), and serum antibodies against M-type phospholipase A2 receptor levels (aPLA2Rab) (MD: 19.24, 95% CI: 33.56 to -4.93, I2 = 87%, P = 0.008). Moreover, the efficacy of combined TCM and Western medicine is superior to that of Western medicine alone in reducing the incidence of infection, hepatotoxicity, and thrombosis. Although the primary and secondary outcomes were consistent, the evidence was generally moderate.ConclusionThe results of this study suggest that TCM alone or in combination with Western medicine may be a feasible alternative therapeutic approach for the treatment of IMN. Nevertheless, additional, rigorously designed, high-quality, and extensive clinical trials are imperative to provide substantial evidence regarding the effectiveness of TCM in managing IMN.

Project description:BackgroundM-type phospholipase A2 receptor (PLA2R) is known as a major antigen on podocytes, which is involved with the pathogenesis of idiopathic membranous nephropathy (iMN). Many studies have shown that serum anti-PLA2R autoantibodies (sPLA2R) are prevalent in patients with iMN but are rarely detected in secondary membranous nephropathy (SMN) or other glomerulonephritis. The anti-PLA2R is considered as a promising serum biomarker in iMN but reports about its diagnostic value are variable and inconsistent.ObjectiveTo evaluate the diagnostic test accuracy (DTA) of anti-PLA2R and glomerular PLA2R antigen (gPLA2R) for diagnosing iMN.MethodMEDLINE, EMBASE, WEB OF SCIENCE, and COCHRANE LIBRARY were searched from 2009 January to February 2018. Heterogeneity was evaluated by Q test and I2. Source of heterogeneity was explored by subgroup analysis and meta-regression. Meta-analysis was executed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement.ResultsTotally, 35 studies were retrieved under the pre-set study eligibility criteria. Twenty-eight studies were included to evaluate the DTA of anti-PLA2R for differentiating iMN from non-iMN. They indicated a pooled sensitivity of 65% (63-67%), specificity of 97% (97-98%), positive likelihood ratio of 15.65 (9.95-24.62), and negative likelihood ratio of 0.37 (0.32-0.42) with a diagnostic OR (sDOR) of 50.41 (31.56 to 80.52) and AUC of 0.9393. No threshold effect was detected. The heterogeneity analysis for sDOR showed that I2 = 50.3% and Cochran-Q = 54.29, df = 27 (p = 0.0014). Heterogeneity was significant. Meta-regression revealed that sample size might be the potential source of heterogeneity. Subgroup analysis demonstrated that method type and ratio of patients with nephrotic-range proteinuria at baseline might be the source of heterogeneity. Sixteen studies reported the diagnostic value of glomerular PLA2R antigen for differentiating iMN from non-iMN. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, sDOR, and AUC were 79% (76-81%), 90% (88-92%), 8.17 (5.60-11.93), 0.25 (0.19-0.33), 39.37 (22.18-60.13), and 0.9278. Heterogeneity analysis showed that Cochran-Q = 35.36; df = 15 (p = 0.002), and I2 for sDOR was 57.6%.ConclusionsPLA2R and gPLA2R demonstrated a good diagnostic accuracy in differentiating iMN and non-iMN.

Dataset Information

Meta-Analysis of the Diagnostic Efficiency of THSD7A-AB for the Diagnosis of Idiopathic Membranous Nephropathy.

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Meta-Analysis of the Diagnostic Efficiency of THSD7A-AB for the Diagnosis of Idiopathic Membranous Nephropathy.

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