Response to immunosuppressive therapy in PLA2R- associated and non-PLA2R- associated idiopathic membranous nephropathy: a retrospective, multicenter cohort study

Wang, Jia; Xie, Qionghong; Sun, Zhonghua; Xu, Ning-Xin; Li, Yan; Wang, Liang; Liu, Shaojun; Xue, Jun; Hao, Chuan‐Ming

doi:10.1186/s12882-017-0636-0

Cited by 18 publications

(20 citation statements)

References 29 publications

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“…The relevant antibodies can be detected in the circulation of patients with iMN, and they form in situ immune complexes in the glomerular subepithelium, damaging podocytes via membrane attack complexes to induce proteinuria [12]. Given its high sensitivity and specificity, the presence of PLA2R in the glomerulus has guiding significance in the diagnosis and evaluation of iMN [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy

Zhang

Liu

Liang

et al. 2020

Kidney Blood Press Res

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Objective: Co-deposition of mannose-binding lectin (MBL) and IgG4 anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies under subepithelial cells has been observed in patients with idiopathic membranous nephropathy (iMN), but the relationships of MBL deposition to iMN severity and progression remain unclear. Methods: Patients diagnosed with iMN who underwent renal puncture were enrolled and followed up for a median of 17 months (interquartile range [IQR], 9–25 months). Serum anti-PLA2R and anti-thrombospondin type-1 domain-containing 7A antibodies and MBL were detected by ELISA. Glomerular MBL and anti-PLA2R antibodies were detected by immunofluorescence. Proteinuria remission, including complete remission (CR), was defined as a clinical event. Clinicopathological characteristics and kidney outcomes were compared between patients with and without MBL deposition. Results: In 67 prevalent patients with biopsy-proven iMN, serum anti-PLA2R antibodies and anti-THSD7A antibodies were present in 37 (55.3%) and 1 (1.4%) patient with iMN. The positivity of glomerular MBL deposition and tissue anti-PLA2R antibody was 53 (79.1%) and 49 (73.1%), respectively. No significant difference was found between the MBL-positive and negative groups in the albumin level (26.5 ± 6.6 and 28.6 ± 6.1 g/L), eGFR (104.8 ± 17.4 and 114.6 ± 16.1 mL/min/1.73 m2), 24-h proteinuria (5.35 and 4.25 g/day), or serum MBL level corrected by serum Cr 4.92 (IQR, 0.86, 8.90) and 2.28 (IQR, 0.4, 5.62). In a Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure, eGFR, immunosuppressive agent use, 24-h proteinuria, and anti-PLA2R antibody concentration, glomerular MBL deposition was independently associated with ICR of proteinuria (HR, 6.31; 95% CI, 1.1–36.1; p = 0.039). Conclusions: The MBL pathway of complement activation is commonly initiated in patients with iMN, and patients with MBL deposition reach ICR faster than patients without MBL deposition.

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Section: Introductionmentioning

confidence: 99%

Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy

Zhang

Liu

Liang

et al. 2020

Kidney Blood Press Res

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“…A retrospective study included 572 IMN patients had found that patients who did not achieve remission had a higher positive rate of renal PLA2R antigen than those achieved remission . Another retrospective cohort study had also identified a higher remission rate in non‐PLA2R‐associated IMN . The reason for lower probability to achieve remission in PLA2R‐associated IMN patients still remained unclear.…”

Section: Discussionmentioning

confidence: 99%

“…25 Another retrospective cohort study had also identified a higher remission rate in non-PLA2R-associated IMN. 26 The reason for lower probability to achieve remission in PLA2R-associated IMN patients still remained unclear. Autoantibody may target a specific conformational region of PLA2R protein on the podocyte surface and trigger the formation of immune complexes, which may lead to the activation of complement pathway and the enhancement of glomerular permeability to plasma proteins.…”

Section: Discussionmentioning

confidence: 99%

Clinical value of renal phospholipase A2 receptor deposit in the prognosis evaluation and treatment options of idiopathic membranous nephropathy: A retrospective cohort study

Xie

Dong

et al. 2020

Nephrology

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Aim Phospholipase A2 receptor (PLA2R) is a target antigen for idiopathic membranous nephropathy (IMN). However, the association between renal PLA2R antigen and disease prognosis had not been fully investigated. In addition, there was a paucity of studies investigating the difference of therapeutic effects between cyclophosphamide and cyclosporine A in PLA2R‐associated IMN. Methods This retrospective cohort study recruited 300 eligible patients diagnosed with biopsy‐proven IMN between September 2015 and July 2018 in Guangdong Provincial People's Hospital. The remission of proteinuria was compared between PLA2R‐associated and non‐PLA2R‐associated IMN. The difference of therapeutic effects between cyclophosphamide and cyclosporine A were also investigated in PLA2R‐associated IMN. Results The positive rate of renal PLA2R antigen in recruited IMN patients was 82.3%. Non‐PLA2R‐associated IMN patients had a higher probability to achieve remission than PLA2R‐associated IMN patients (Log–rank test, P = .013). Multivariate COX analysis showed that renal PLA2R antigen was an independent risk factor for not achieving remission in IMN patients (Hazard Ratio: 1.619; 95% confidence interval: 1.133 to 2.313; P = .008). In PLA2R‐associated IMN, patients receiving cyclophosphamide had a higher probability to achieve remission compared with those receiving cyclosporine A (Log–rank test, P = .018) while there was no difference in renal survival. Multivariate COX regression analysis showed that compared with cyclosporine A, patients receiving cyclophosphamide had a higher probability to achieve remission. Conclusion Phospholipase A2 receptor ‐associated IMN patients had a lower probability to achieve remission compared with non‐PLA2R‐associated IMN. Compared with cyclosporine A, cyclophosphamide exerted better therapeutic effects in remission of proteinuria and may be the preferred immunosuppressant for PLA2R‐associated IMN.

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“…As compared to patients with non-PLA2R1 related MN, those with PLA2R1 related MN responded slower to immunosuppressive therapy [ 135 , 136 ]. Moreover, patients presenting high titer of autoantibodies have more severe disease and a longer time to disease remission [ 137 ].…”

Section: Anti-pla2r1 and Anti-thsd7a Antibodies And Primary Mnmentioning

confidence: 99%

Membranous Nephropathy and Anti-Podocytes Antibodies: Implications for the Diagnostic Workup and Disease Management

Pozdzik

Brochériou

David

et al. 2018

BioMed Research International

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The discovery of circulating antibodies specific for native podocyte antigens has transformed the diagnostic workup and greatly improved management of idiopathic membranous nephropathy (iMN). In addition, their identification has clearly characterized iMN as a largely autoimmune disorder. Anti-PLA2R1 antibodies are detected in approximately 70% to 80% and anti-THSD7A antibodies in only 2% of adult patients with iMN. The presence of anti-THSD7A antibodies is associated with increased risk of malignancy. The assessment of PLA2R1 and THSD7A antigen expression in glomerular immune deposits has a better sensitivity than measurement of the corresponding autoantibodies. Therefore, in the presence of circulating anti-podocytes autoantibodies and/or enhanced expression of PLA2R1 and THSD7A antigens MN should be considered as primary MN (pMN). Anti-PLA2R1 or anti-THSD7A autoantibodies have been proposed as biomarkers of autoimmune disease activity and their blood levels should be regularly monitored in pMN to evaluate disease activity and predict outcomes. We propose a revised clinical workup flow for patients with MN that recommends assessment of kidney biopsy for PLA2R1 and THSD7A antigen expression, screening for circulating anti-podocytes antibodies, and assessment for secondary causes, especially cancer, in patients with THSD7A antibodies. Persistence of anti-podocyte antibodies for 6 months or their increase in association with nephrotic proteinuria should lead to the introduction of immunosuppressive therapies. Recent data have reported the efficacy and safety of new specific therapies targeting B cells (anti-CD20 antibodies, inhibitors of proteasome) in pMN which should lead to an update of currently outdated treatment guidelines.

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Response to immunosuppressive therapy in PLA2R- associated and non-PLA2R- associated idiopathic membranous nephropathy: a retrospective, multicenter cohort study

Cited by 18 publications

References 29 publications

Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy

Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy

Clinical value of renal phospholipase A2 receptor deposit in the prognosis evaluation and treatment options of idiopathic membranous nephropathy: A retrospective cohort study

Membranous Nephropathy and Anti-Podocytes Antibodies: Implications for the Diagnostic Workup and Disease Management

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