Abstract
Background: This study aimed to evaluate clinical features and prognosis and therapy option of patients with different risk ranks based on antibody against the M-type phospholipase-A2-receptor (PLA2Rab) level in seropositive M-type phospholipase-A2-receptor (PLA2R)-associated membranous nephropathy (MN) in a large sample size, multi-center study. Method: Based on the unvalidated cut-off value of PLA2Rab above 150 RU/ml as one of the clinical criteria for high risk of progressive kidney function loss in MN according to 2020 Kidney Disease: Improving Global Outcomes (KDIGO) draft guidelines recommendation, a total of 447 patients who received cyclophosphamide (CTX) or tacrolimus (TAC) combined with corticosteroids treatment for 12 months were divided into high titer (>150 RU/ml) group and non-high titer (20–150 RU/ml) group, which were subdivided into CTX subgroup and TAC subgroup. The overall cohort was classified into CTX group and TAC group as well. Clinical parameters levels and remission rates were recorded at 3, 6, and 12 months follow-up. PLA2Rab was tested by enzyme-linked immunosorbent assay. Results: Patients with high titer PLA2Rab were associated with more severe proteinuria and hypoalbuminemia compared to those with non-high titer antibody, accompanied by lower complete remission (CR) and total remission (TR) rates at 3, 6, and 12 months, which even took longer to remission. Similar remission rates differences between the two titer groups were observed in the CTX and TAC groups, respectively. PLA2Rab level at baseline was an independent predictive factor for CR and TR. In the high titer group, CR and TR rates in the CTX subgroup were significantly higher than those in the TAC subgroup at 12 months, although serious adverse events were more frequent in the former. Conclusion: High-risk rank patients with PLA2Rab level above 150 RU/ml have higher disease activity and worse prognosis among patients with seropositive PLA2R-associated MN, even under different immunosuppressive therapeutic models; moreover, CTX combined with corticosteroids was preferred compared to TAC plus corticosteroids, although serious adverse events were more frequent in the former. Additionally, baseline PLA2Rab level was an independent predictive factor for clinical remission.
Highlights
In 2009, Beck et al (2009) first discovered that M-type phospholipase A2 receptor (PLA2R) was a key target glomerular podocyte antigen, which was abundantly expressed in 70% of patients with primary membranous nephropathy (MN)
A cumulative number of studies have reported a relationship between PLA2Rab levels and clinical parameters, such as 24-h urinary protein and serum albumin (Hofstra et al, 2011; Kaga et al, 2019), and the detection of serum PLA2Rab might help to assess the therapeutic response (Ruggenenti et al, 2015; De Vriese et al, 2017; Guo et al, 2019; van de Logt et al, 2019), time to remission (Qin et al, 2011), prognosis stratification (Liang et al, 2019), and personalized treatment design (Glassock, 2014)
On the other hand, compared to Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in 2012, there is an important change concerning calcineurin inhibitors (CNIs) in moderate- to high-risk patients, in which CNIs might not seem to be the best therapy for primary MN, and the most effective immunosuppressive therapy is controversial
Summary
In 2009, Beck et al (2009) first discovered that M-type phospholipase A2 receptor (PLA2R) was a key target glomerular podocyte antigen, which was abundantly expressed in 70% of patients with primary membranous nephropathy (MN). Subsequent studies showed that antibody against the M-type phospholipase-A2-receptor (PLA2Rab) was found seropositivity in 57%–88.5% in primary MN (Qin et al, 2011; Ramachandran et al, 2016; Huang et al, 2017; Li et al, 2018). Different PLA2Rab rank cut-off values have been reported in the respective studies (Hofstra et al, 2012; Hoxha et al, 2014b; Ruggenenti et al, 2015; Ramachandran et al, 2016; Dahan et al, 2017; van de Logt et al, 2018). This study aimed to evaluate clinical features and prognosis and therapy option of patients with different risk ranks based on antibody against the M-type phospholipase-A2-receptor (PLA2Rab) level in seropositive M-type phospholipase-A2receptor (PLA2R)-associated membranous nephropathy (MN) in a large sample size, multicenter study
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