Serum anti-phospholipase A2 receptor (PLA2R) antibody detected at diagnosis as a predictor for clinical remission in patients with primary membranous nephropathy: a meta-analysis

Abstract

Background The diagnostic value of serum M-type phospholipase A2 receptor antibody (sPLA2R-ab) expression in patients with primary membranous nephropathy (PMN) has been established. However, the association between sPLA2R-ab and clinical remission remains uncertain. Methods We systematically searched the literature for clinical trials regarding the correlation between sPLA2R-ab expression and clinical remission of PMN patients. Meta-analysis was performed to determine this association. Subgroup analysis, funnel plots, and sensitivity analysis were also performed to investigate heterogeneity or bias. Results A total of 11 trials involving 824 patients were included. Patients with positive sPLA2R-ab had a poor clinical remission rate (RR = 0.76, 95%CI 0.68–0.86, P < 0.0001; I2 = 39%), a higher titer of sPLA2R-ab had a lower chance of clinical remission (RR = 0.72, 95%CI 0.59–0.87, P = 0.0006; I2 = 42%),and a higher risk of renal failure (RR = 4.85, 95% CI, 1.83–12.85, P = 0.002; I2 = 0%), without affecting relapse (RR = 0.97, 95% CI, 0.55–1.70; P = 0.92, I2 = 0%). Subgroup analysis by treatment strategies, assay methods, ethnicity, gender, renal function, the approach of ruling out SMN, and the ratio of patients with nephrotic-range proteinuria at baseline showed no significant association between these factors with the prognostic value of sPLA2R-ab for PMN patients. No significant publication bias was found. Conclusion This meta-analysis adds to the evidence for current guidelines that sPLA2R-ab acts as not only a diagnostic marker but also a pivotal predictor for clinical remission. Therefore, sPLA2R-ab can be considered as a prognostic factor for stratifying PMN patients.

PLA2R antibody, PLA2R rs4664308 polymorphism and PLA2R mRNA levels in Tunisian patients with primary membranous nephritis

“…Also, the presence of anti-PLA2R Ab at diagnosis was significantly associated with the non-remission outcome, p = 0.002. Even there is a limitation due to the presence of some non-nephrotic patients at baseline, our result corroborates those of previous studies which were confirmed by 2 recent meta-analyzes [23,24]. In fact, in the metanalysis of Liang et al [23] including 11 published studies, the presence of anti-PLA2R Ab decreased the chance of clinical remission by 0.76-fold [0.68-0.86], p<0.0001.…”

“…Even there is a limitation due to the presence of some non-nephrotic patients at baseline, our result corroborates those of previous studies which were confirmed by 2 recent meta-analyzes [23,24]. In fact, in the metanalysis of Liang et al [23] including 11 published studies, the presence of anti-PLA2R Ab decreased the chance of clinical remission by 0.76-fold [0.68-0.86], p<0.0001. Similarly, the meta-analysis of Li et al [24] showed that PMN patients with negative baseline anti-PLA2R Ab had 1.65 times (95% CI: 1.46-1.87, p<0.05) increased chance of reaching complete remission and 1.93 times (95% CI: 1.53-2.45, p<0.05) increased chance of achieving spontaneous remission.…”

“…Significant higher levels of anti-PLA2 Ab in non-remission patients was also reported by previous studies [25,26] and confirmed by the meta-analysis of Liang et al [23]. In this meta-analysis, PMN patients with high titers of PLA2R Ab had 0.72-fold (95% CI: 0.59-0.87, p = 0.0006) decreased chance of achieving clinical remission [23]. In a recent study [26], sera from patients with high levels of anti-PLA2R Ab showed a multiple reactivity to CTLD1 and CTLD7 domains in addition to CysR domain, p<0.001.…”

“…Thus, for a threshold of 239.95 RU/ml, the sensitivity and the specificity of anti-PLA2R Ab in predicting non-remission were 100% and 87.5%. Significant higher levels of anti-PLA2 Ab in non-remission patients was also reported by previous studies [25,26] and confirmed by the meta-analysis of Liang et al [23]. In this meta-analysis, PMN patients with high titers of PLA2R Ab had 0.72-fold (95% CI: 0.59-0.87, p = 0.0006) decreased chance of achieving clinical remission [23].…”

Single-nucleotide polymorphism rs4664308 in PLA2R1 gene is associated with the risk of idiopathic membranous nephropathy: a meta-analysis

“…Moreover, a meta-analysis including 23 studies showed that IMN patients who tested negative for anti-PLA2R1 Ab at the time of renal biopsy had a higher risk ratio (RR) of clinical remission (defined as proteinuria < 3.5 g/day and > 50% reduction from baseline proteinuria) than those who tested positive for anti-PLA2R1 Ab (RR, 1.31; 95% CI 1.12–1.46; I 2 = 74%) 29 . Another meta-analysis including eleven studies also showed that the anti-PLA2R1 Ab-positive group had a lower RR of clinical remission (defined as proteinuria < 3.5 g/day) than the anti-PLA2R1 Ab-negative group among IMN patients (RR, 0.76; 95% CI 0.68–0.86; I 2 = 39%) 30 . In addition, Seitz-Polski et al showed that analysis of PLA2R1 epitope spreading was also a powerful tool for predicting clinical remission (defined as a urinary protein/creatinine ratio < 4 g/g and an estimated glomerular filtration rate > 45 ml/min/1.73 m 2 ) in a cohort with 69 IMN patients who tested positive for anti-PLA2R1 Ab 31 .…”