Journal of Diagnostics Concepts & Practice >
Recent advances in diagnosis and treatment of primary membranous nephropathy
Received date: 2025-02-16
Accepted date: 2025-05-14
Online published: 2025-06-25
Primary membranous nephropathy (PMN) has seen a significant global rise in incidence, with data from China showing an annual growth of 13%, making it the leading cause of nephrotic syndrome in people over 40 years old. The diagnosis of PMN traditionally depends on renal biopsy, but recent studies have provided new directions for non-invasive diagnosis. The discovery of anti-phospholipase A2 receptor (PLA2R) antibodies in 2009 marked a milestone in PMN research, and the identification of other target antigens (such as THSD7A and NELL-1) further advanced the understanding of the pathogenesis. Serum PLA2R antibody detection has high specificity but limited sensitivity, potentially lea-ding to missed diagnosis of non-PLA2R-related cases. The combined disease risk score integrating susceptibility loci identified through genome-wide association studies (GWAS) (such as PLA2R1 and HLA-DQA1) with serum antibodies has significantly improved the accuracy of non-invasive diagnosis (area under the receiver operating characteristic curve reaching 0.96). Additionally, gut microbiome analysis demonstrates diagnostic potential, though its clinical application requires further optimization. In terms of advances in prognostic assessment, PMN exhibits remarkable heterogeneity in its natural course, with approximately one-third of patients achieving spontaneous remission and another one-third progressing to renal function decline. Age, proteinuria level, eGFR, PLA2R antibody titer, and the extent of tubulointerstitial lesions are key prognostic predictors. A model combining clinical risk score (CRS) with clinical parameters (such as age, proteinuria, and eGFR) can effectively identify high-risk patients and guide precision treatment. Traditional regimens (such as hormone combined with alkylating agents or calcineurin inhibitors) are effective but have significant toxic side effects. In recent years, anti-CD20 monoclonal antibodies, represented by rituximab (RTX), have become first-line treatments, substantially improving efficacy, though they remain ineffective for some patients. Novel biologics and complement pathway inhibitors provide new options for treatment-resistant patients. Combination strategies (such as RTX combined with tacrolimus) are under investigation, but the balance between efficacy and safety needs to be carefully considered. Future efforts should focus on further optimizing risk stratification and individualized treatment strategies to improve the long-term prognosis of PMN patients.
HU Xiaofan , XU Jing . Recent advances in diagnosis and treatment of primary membranous nephropathy[J]. Journal of Diagnostics Concepts & Practice, 2025 , 24(03) : 249 -254 . DOI: 10.16150/j.1671-2870.2025.03.002
| [1] | HANKO J B, MULLAN R N, O'ROURKE D M, et al. The changing pattern of adult primary glomerular disease[J]. Nephrol Dial Transplant, 2009, 24(10):3050-3054. |
| [2] | SHIIKI H, SAITO T, NISHITANI Y, et al. Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan[J]. Kidney Int, 2004, 65(4):1400-1407. |
| [3] | PAN X, XU J, REN H, et al. Changing spectrum of biopsy-proven primary glomerular diseases over the past 15 years: a single-center study in China[J]. Contrib Nephrol, 2013,181:22-30. |
| [4] | XU X, WANG G, CHEN N, et al. Long-term exposure to air pollution and increased risk of membranous nephropathy in China[J]. J Am Soc Nephrol, 2016, 27(12):3739-3746. |
| [5] | KERJASCHKI D, FARQUHAR M G. The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border[J]. Proc Natl Acad Sci U S A, 1982, 79(18):5557-5561. |
| [6] | DEBIEC H, GUIGONIS V, MOUGENOT B, et al. Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies[J]. N Engl J Med, 2002, 346(26):2053-2060. |
| [7] | DEBIEC H, RONCO P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy[J]. N Engl J Med, 2011, 364(7):689-690. |
| [8] | TOMAS N M, BECK L H JR, MEYER-SCHWESINGER C, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy[J]. N Engl J Med, 2014, 371(24):2277-2287. |
| [9] | SETHI S, DEBIEC H, MADDEN B, et al. Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy[J]. Kidney Int, 2020, 97(1):163-174. |
| [10] | BOBART S A, DE VRIESE A S, PAWAR A S, et al. Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies[J]. Kidney Int, 2019, 95(2):429-438. |
| [11] | STANESCU H C, ARCOS-BURGOS M, MEDLAR A, et al. Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy[J]. N Engl J Med, 2011, 364(7):616-626. |
| [12] | LV J, HOU W, ZHOU X, et al. Interaction between PLA2R1 and HLA-DQA1 variants associates with anti-PLA2R antibodies and membranous nephropathy[J]. J Am Soc Nephrol, 2013, 24(8):1323-1329. |
| [13] | XIE J, LIU L, MLADKOVA N, et al. The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis[J]. Nat Commun, 2020, 11(1):1600. |
| [14] | SHANG J, ZHANG Y, GUO R, et al. Gut microbiome analysis can be used as a noninvasive diagnostic tool and plays an essential role in the onset of membranous nephropathy[J]. Adv Sci (Weinh), 2022, 9(28):e2201581. |
| [15] | HU X, XU J, WANG W, et al. Combined serologic and genetic risk score and prognostication of phospholipase A2 receptor-associated membranous nephropathy[J]. Clin J Am Soc Nephrol, 2024, 19(5):573-582. |
| [16] | ZHANG X D, CUI Z, ZHANG M F, et al. Clinical implications of pathological features of primary membranous nephropathy[J]. BMC Nephrol, 2018, 19(1):215. |
| [17] | WASSERSTEIN A G. Membranous glomerulonephritis[J]. J Am Soc Nephrol, 1997, 8(4):664-674. |
| [18] | HEERINGA S F, BRANTEN A J, DEEGENS J K, et al. Focal segmental glomerulosclerosis is not a sufficient predictor of renal outcome in patients with membranous nephropathy[J]. Nephrol Dial Transplant, 2007, 22(8):2201-2207. |
| [19] | DUMOULIN A, HILL G S, MONTSENY J J, et al. Clinical and morphological prognostic factors in membranous nephropathy: significance of focal segmental glomerulosclerosis[J]. Am J Kidney Dis, 2003, 41(1):38-48. |
| [20] | KANIGICHERLA D, GUMMADOVA J, MCKENZIE E A, et al. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy[J]. Kidney Int, 2013, 83(5):940-948. |
| [21] | XIAOFAN H, JING X, CHENNI G, et al. New risk score for predicting progression of membranous nephropathy[J]. J Transl Med, 2019, 17(1):41. |
| [22] | MURPHY B F, FAIRLEY K F, KINCAIDSMITH P S. Idiopathic membranous glomerulonephritis: long-term follow-up in 139 cases[J]. Clin Nephrol, 1988,30:175-181. |
| [23] | PONTICELLI C, ALTIERI P, SCOLARI F, et al. A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy[J]. J Am Soc Nephrol, 1998, 9(3):444-450. |
| [24] | FALK R J, HOGAN S L, MULLER K E, et al. Treatment of progressive membranous glomerulopathy. A randomi-zed trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. The Glomerular Disease Collaborative Network[J]. Ann Intern Med, 1992, 116(6):438-445. |
| [25] | XU J, ZHANG W, XU Y, et al. Tacrolimus combined with corticosteroids in idiopathic membranous nephropathy: a randomized, prospective, controlled trial[J]. Contrib Nephrol, 2013,181:152-162. |
| [26] | FERVENZA F C, APPEL G B, BARBOUR S J, et al. Rituximab or cyclosporine in the treatment of membranous nephropathy[J]. N Engl J Med, 2019, 381(1):36-46. |
| [27] | SCOLARI F, DELBARBA E, SANTORO D, et al. Ritu-ximab or cyclophosphamide in the treatment of membranous nephropathy: The RI-CYCLO randomized trial[J]. J Am Soc Nephrol, 2021, 32(4):972-982. |
| [28] | HU X, REN H, XU J, et al. Treatment of membranous nephropathy in Chinese patients: comparison of rituximab and intravenous cyclophosphamide with steroids[J]. Kidney Dis (Basel), 2024, 10(5):359-368. |
| [29] | HU X, ZHANG M, XU J, et al. Comparison of obinutuzumab and rituximab for treating primary membranous nephropathy[J]. Clin J Am Soc Nephrol, 2024, 19(12):1594-1602. |
| [30] | XU M, WANG Y, WU M, et al. Obinutuzumab versus rituximab for the treatment of refractory primary membranous nephropathy[J]. Nephrol Dial Transplant, 2025, 40(5):978-986. |
| [31] | SU X, WU B, TIE X, et al. Obinutuzumab as initial or second-line therapy in patients with primary membranous nephropathy[J]. Kidney Int Rep, 2024, 9(8):2386-2398. |
| [32] | PODESTà M A, TRILLINI M, PORTALUPI V, et al. Ofatumumab in rituximab-resistant and rituximab-intolerant patients with primary membranous nephropathy: a case series[J]. Am J Kidney Dis, 2024, 83(3):340-349.e1. |
| [33] | DAHAN K, DEBIEC H, PLAISIER E, et al. Rituximab for severe membranous nephropathy: A 6-month trial with extended follow-up[J]. J Am Soc Nephrol, 2017, 28(1):348-358. |
| [34] | SETHI S, KUMAR S, LIM K, et al. Obinutuzumab is Effective for the treatment of refractory membranous nephropathy[J]. Kidney Int Rep, 2020, 5(9):1515-1518. |
| [35] | BARRETT C, WILLCOCKS L C, JONES R B, et al. Effect of belimumab on proteinuria and anti-phospholipase A2 receptor autoantibody in primary membranous nephropathy[J]. Nephrol Dial Transplant, 2020, 35(4):599-606. |
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