scholarly journals Efficacy and Safety of Different Immunosuppressive Therapies in Patients With Membranous Nephropathy and High PLA2R Antibody Titer

2022 ◽  
Vol 12 ◽  
Author(s):  
Le Deng ◽  
Qipeng Huang ◽  
Jiang Wang ◽  
Kaiping Luo ◽  
Jiarong Liu ◽  
...  
Keyword(s):  
High Risk ◽  
Adverse Events ◽  
Phospholipase A2 ◽  
Predictive Factor ◽  
Membranous Nephropathy ◽  
High Titer ◽  
Independent Predictive Factor ◽  
Serious Adverse Events ◽  
Phospholipase A2 Receptor ◽  
Remission Rates

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.

Anti-Phospholipase A2 Receptor Antibody as Prognostic Indicator in Idiopathic Membranous Nephropathy

2015 ◽  
Vol 42 (3) ◽  
pp. 250-257 ◽  
Author(s):  
Yang Gyun Kim ◽  
Young-Wook Choi ◽  
Se-Yun Kim ◽  
Ju Young Moon ◽  
Chun-Gyoo Ihm ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Remission Rate ◽  
High Titer ◽  
Severe Disease ◽  
Idiopathic Membranous Nephropathy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Receptor Antibody ◽  
Phospholipase A2 Receptor

Background: Anti-phospholipase A2 receptor antibody (PLA2R-Ab) is useful in diagnosing idiopathic membranous nephropathy (IMN). We investigated the clinical relevance of PLA2R-Ab enzyme-linked immunosorbent assay (ELISA) in patients with IMN. Methods: We measured PLA2R-Ab with an ELISA kit from the serum of 160 patients with IMN (n = 93), secondary MN (n = 14) and other glomerulonephritis (n = 41) as well as healthy controls (n = 12) at the time of renal biopsy and investigated the correlation of titers of PLA2R-Ab with clinical parameters. Results: PLA2R-Ab was positive in 41 of 93 patients (44.1%) with IMN. No samples from the patients with secondary MN and other glomerulonephritis or healthy controls were positive with the ELISA test. The PLA2R-Ab-positive patients showed severe disease activity and a low remission rate. The PLA2R-Ab titer positively correlated with proteinuria and was negatively associated with renal function and serum albumin. The patients with a high titer of PLA2R-Ab had significantly decreased remission rates. The cumulative probabilities of remission was significantly lower in patients with PLA2R-Ab (p = 0.01) and even so in patients with a high titer of PLA2R-Ab (p = 0.04). When we compared the ELISA titers with Western blot (WB) data of 43 patients who had been enrolled in our previous study, 18 and 30 patients were positive on ELISA (41.9%) and WB (69.8%), respectively. WB and ELISA had a concordance rate of 72.1% and were positively correlated (r = 0.590, p < 0.001). Conclusion: The presence, as well as a high titer, of PLA2R-Ab on ELISA was associated with poor prognosis of IMN. Assessment of PLA2R-Ab with ELISA is an easy and reliable tool for the diagnosis and guidance of therapeutic plans.

Phospholipase A2 receptor antibody mediated membranous nephropathy associated with cemiplimab

2021 ◽  
pp. 239936932110046
Author(s):  
Marco Bonilla ◽  
Boonyanuth Maturostrakul ◽  
Neelofar Khan ◽  
Vanesa Bijol ◽  
Kenar D Jhaveri ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Checkpoint Inhibitors ◽  
Acute Interstitial Nephritis ◽  
Prior History ◽  
Close Monitoring ◽  
Glomerular Diseases ◽  
Phospholipase A2 Receptor ◽  
History Of

Background: Immune checkpoint inhibitors (ICI) are a fast growing therapy used in several types of malignancies. The majority of immune related adverse events observed in the kidney are due to acute interstitial nephritis. Glomerular diseases although less common have also been described. Case Presentation: We present a case of phospholipase A2 receptor positive membranous nephropathy triggered by ICI therapy cemiplimab (PD1 inhibitor) in a 88 year old man with no prior history of proteinuria or glomerular disease. The patient responded to steroid monotherapy with rapid clinical and immunological remission. Conclusion: While patients undergoing ICI therapy warrant close monitoring of systemic immune related adverse events, physicians should remain vigilant of kidney related events and obtain a kidney biopsy if clinically indicated.

A novel time-resolved fluoroimmunoassay based on magnetic microspheres method for detecting antibodies against Phospholipase A2 Receptor

2021 ◽  
Author(s):  
ting li ◽  
qingqing wu ◽  
Xue Yang ◽  
Yueming liu ◽  
bo lin ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Disease Activity ◽  
Membranous Nephropathy ◽  
Magnetic Microspheres ◽  
Idiopathic Membranous Nephropathy ◽  
Serum Antibodies ◽  
Time Resolved ◽  
Phospholipase A2 Receptor

Background: The level of serum antibodies against the M-type phospholipase A2 receptor (anti-PLA2R-IgG) is closely related to the disease activity of idiopathic membranous nephropathy (IMN). Therefore, the establishment of a...

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

2021 ◽  
Vol 32 (4) ◽  
pp. 972-982 ◽  
Author(s):  
Francesco Scolari ◽  
Elisa Delbarba ◽  
Domenico Santoro ◽  
Loreto Gesualdo ◽  
Antonello Pani ◽  
...  
Keyword(s):  
Complete Remission ◽  
Adverse Events ◽  
Membranous Nephropathy ◽  
Partial Remission ◽  
Pilot Trial ◽  
Clinical Trial Registry ◽  
Serious Adverse Events ◽  
First Line Therapy ◽  
Registration Number ◽  
Favorable Safety

BackgroundA cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking.MethodsWe randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events.ResultsAt 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen.ConclusionsThis pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial.Clinical Trial registry name and registration number:Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO),NCT03018535

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