Phospholipase A2 Receptor Antibodies and Clinical Prognosis in Patients with Idiopathic Membranous Nephropathy: An Updated Systematic Review and Meta-Analysis

Abstract

Background: Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor (PLA2R-ab) are considered as diagnostic biomarkers of IMN. Objective: Here, we performed an updated meta-analysis to assess the diagnostic value of PLA2R-ab for clinical remission in IMN patients. Method: PubMed, Embase and Cochrane databases were searched for relevant studies published before September 2022. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were determined using a fixed or random effects model. The heterogeneity among studies was explored by subgroup analysis. Results: Sixteen studies involving 1761 IMN participants were included. There were significant differences between PLA2R-ab (+) and PLA2R-ab (-) patients in terms of complete remission (CR) and spontaneous remission. The rates of partial remission (PR) and relapse were similar between the two groups. Patients with PLA2R-ab (-) were at a higher CR rate when treated with a calcineurin inhibitor or a treatment course for 3 months and 6 months, while the spontaneous remission rate was higher in PLA2R-ab seronegative patients from Asia. However, the CR and spontaneous remission rate only significantly declined in IMN patients with the highest titer, but not a middle titer, when compared to those with the lowest titer. Conclusion: In contrast to previous meta-analyses, our results verified that PLA2R-ab can likely predict CR and spontaneous remission in IMN patients, instead of PR and relapse. Race, immunosuppressive agents and duration of treatment may affect the prognostic value of PLA2R-ab. Considering that the remission rate of IMN patients with a middle level of PLA2R-ab was not different from that of patients with the lowest level, a proper cut-off value of PLA2R-ab for prognosis should be clarified.

Urine albumin-to-creatinine ratio diurnal variation rate predicts outcomes in idiopathic membranous nephropathy

“…The black and gray points are the optimal points determined by the maximum Youden's index (sensitivity + specificity-1); on the two points, the estimated probability of NR and UACR diurnal variation rate (%) was 0.331 and 58.5%. NR no remission, UACR urine albumin-to-creatinine ratio spontaneous remission rate were significantly declined in IMN patients with the highest titer [44], indicating that the quantitative measures may be required for prognosis prediction purpose. However, in the present study, even when the titer of anti-PLA2R was incorporated into the univariable logistic regression model, no significant difference was found (odds ratio 2.133 with 95% CI 0.649-7.009, P = 0.212).…”

“…However, no significant difference in the presence of anti-PLA2R-positive rate or the titer of anti-PLA2R was found among the three groups in this study ( P = 0.425 and 0.798, respectively). A meta-analysis indicated that compared to patients with the lowest titer of anti-PLA2R, the CR and spontaneous remission rate were significantly declined in IMN patients with the highest titer [ 44 ], indicating that the quantitative measures may be required for prognosis prediction purpose. However, in the present study, even when the titer of anti-PLA2R was incorporated into the univariable logistic regression model, no significant difference was found (odds ratio 2.133 with 95% CI 0.649–7.009, P = 0.212).…”

Application of CD38 monoclonal antibody in kidney disease

“…It is primarily caused by antibodies targeting the antiphospholipase A2 receptor (PLA2R), resulting in the accumulation of immune complexes in the glomerular basement membrane (32). Recent research has shown that patients who test positive for PLA2R antibodies experiencing a reduced rate of natural remission compared to individuals who test negative for antibodies (33).Standard therapies, including corticosteroids and cyclophosphamide, may not achieve immunologic remission in approximately 10% of patients with membranous nephropathy associated with anti-phospholipase A2 receptor antibody (aPLA2R). Research has shown that the blend of rituximab, cyclophosphamide, and corticosteroids in a cycle therapy approach has proven to be highly effective.…”

Nephrotic syndrome: ethiological factors and differential diagnosis

“…Первичная мембранозная нефропатия, являющаяся основной причиной НС у людей старшего возраста (пик заболеваемости в возрасте 40-60 лет), встречается в несколько раз чаще (70-80% случаев) вторичной нефропатии, которая развивается при аутоиммунных заболеваниях (прежде всего СКВ), злокачественных опухолях, инфекциях и под действием лекарственных средств [14]. Примерно у 80% пациентов с первичной мембранозной нефропатией обнаруживают IgG4-антитела к подоцитарному трансмембранному рецептору фосфолипазы А2 М-типа (PLA2R), высокий титр которых ассоциируется с развитием НС, повышенным риском хронической почечной недостаточности и ухудшением ответа на иммуносупрессивную терапию [15]. Кроме того, наличие антител к PLA2R подтверждает диагноз первичной мембранозной нефропатии и позволяет планировать лечение без его гистологической верификации [8].…”