Dataset Information

Antibody-Guided Therapy in Phospholipase A2 Receptor-Associated Membranous Nephropathy.

ABSTRACT:

Introduction

A 6-month course of cyclophosphamide (CP) and steroids is effective in primary membranous nephropathy (MN), but unappealing because of long-term side effects. We evaluated efficacy of an "antibody-guided" treatment schedule.

Methods

Patients with phospholipase A2 receptor (PLA2R)-related MN and high risk of progression were treated with CP 1.5 mg/kg/d and steroids in cycles of 8 weeks. Anti-PLA2R antibodies were measured by indirect immunofluorescence (IIFT) at 8, 16, and 24 weeks, and a negative test resulted in withdrawal of CP, and rapid tapering of prednisone. In patients with persistent anti-PLA2R antibodies at 24 weeks, CP was switched to mycophenolate mofetil. Treatment was repeated in patients with a relapse.

Results

Our analysis included 65 patients (48 males, 17 females), age 61 ± 12 years, estimated glomerular filtration rate (eGFR) 46 ml/min per 1.73 m² (35-68), urine protein-to-creatinine ratio 7.7 grams/10 mmol creatinine (5.4-11.1) and serum albumin 20 g/l (16-26). Immunologic remission rate was 71% after 8 weeks, 86% after 16 weeks, 88% after 24 weeks, and 94% after 3 years. Twenty-seven patients (42%) had persistent clinical remission after only 8 weeks of therapy. Sixteen patients needed a second course of therapy because of immunologic or clinical relapse. Follow-up was 37 (26-58) months. Overall partial remission rate was 92%. One patient developed end-stage kidney disease. Antibody-guided therapy (ABG) was as effective as the standard 6-month course, whereas providing a lower cumulative dose of CP (11.1 [8.0-18.5] vs. 18.9 [14.2-23.6] grams).

Conclusion

ABG is effective, and allows individualized therapy, with many patients responding to 8 weeks of CP-based therapy.

SUBMITTER: Vink CH

PROVIDER: S-EPMC10014436 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Antibody-Guided Therapy in Phospholipase A2 Receptor-Associated Membranous Nephropathy.

Vink Coralien H CH Logt Anne-Els van de AV van der Molen Renate G RG Hofstra Julia M JM Wetzels Jack F M JFM

Kidney international reports 20221213 3

<h4>Introduction</h4>A 6-month course of cyclophosphamide (CP) and steroids is effective in primary membranous nephropathy (MN), but unappealing because of long-term side effects. We evaluated efficacy of an "antibody-guided" treatment schedule.<h4>Methods</h4>Patients with phospholipase A2 receptor (PLA2R)-related MN and high risk of progression were treated with CP 1.5 mg/kg/d and steroids in cycles of 8 weeks. Anti-PLA2R antibodies were measured by indirect immunofluorescence (IIFT) at 8, 16, ...[more]

PMID: 36938074

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Project description:Background and Objective Membranous nephropathy (MN) is the pathology type with the highest incidence of thrombotic events in nephrotic syndrome (NS). While patients with MN are prone to developing thromboembolic complications, the specific mechanism remains unclear. Many studies have shown a high titer of PLA2R antibody aggravates proteinuria and hypoalbuminemia and predicts a lower likelihood of clinical remission in patients with PLA2R-associated MN. Proteinuria and hypoalbuminemia also increase the risk of thrombotic events. In our previous review, we found secretory phospholipase A2 (sPLA2) may act as a ligand for PLA2R, and binding of sPLA2 to PLA2R results in damage to podocytes. sPLA2 can promote the release of AA from membrane phospholipids, and AA is closely related to blood lipid levels and coagulation cascades. The objective of this study is to explain the relationship between phospholipase A2 receptor (PLA2R) and blood hypercoagulability in MN patients and the new theory that secretory phospholipase A2 (sPLA2) and arachidonic acid (AA) may play a role in regulating blood lipid levels and the coagulation cascade in patients with PLA2R-positive MN. Methods Literature retrieval was conducted through China National Knowledge Infrastructure (CNKI) and PubMed. Abstract and Introduction information was then retrieved and the results from the literature searched, classified, and important information summarized. A conclusion was then reached, and a new standpoint put forward. Key Content and Findings We discussed the role of PLA2R antibody and sPLA2 in hypercoagulability in patients with MN and analyzed the following four possible mechanisms: sPLA2 can combine with PLA2R and induce podocyte apoptosis; sPLA2 may promote the production of anti-PLA2R antibodies; sPLA2 may promote the release of AA from membrane phospholipids; and AA induces platelet aggregation. Conclusions PLA2R may exacerbate hypercoagulability in patients with PLA2R-related MN, and sPLA2 plays an important role in the process.

Project description:BackgroundThe value of anti-phospholipase A2 receptor antibody (anti-PLA2R ab) monitoring at 3 months after diagnosis in membranous nephropathy (MN) remains uncertain.MethodsWe retrospectively examined the outcome on 1 August 2020 of 59 adult patients (age 54 (44, 68) years, 69% male, SCr 1.0 (0.9, 1.3) mg/dL) diagnosed with MN (kidney biopsy, positive serum anti-PLA2R ab). The outcomes were: kidney survival; partial and/or complete remission.ResultsMost of the studied patients (97%) received immunosuppression, cyclophosphamide regimens were the most frequent (87%), followed by cyclosporine (10%). The median time to remission was 12.0 months and the cumulative remission rates were 34% at 6, 54% at 12, and 73% at 24 months. Forty (69%) patients had negative anti-PLA2R ab at 3 months, they had similar age, serum creatinine, albumin, proteinuria, and treatment with the group with positive ab at 3 months. In the Cox proportional hazard model, three months anti-PLA2R ab negativization (HR 0.4 (95%CI 0.1, 0.9)) was an independent predictor for remission, while baseline hypoalbuminemia (HR 3.0 (95%CI 1.5, 5.7)) was associated with absence of remission. Six (10%) patients died, mostly due to cardiovascular disease and infections. A total of five (9%) patients started dialysis. Mean kidney survival time was 50.3 months and there was no survival difference in relation to baseline anti-PLA2R ab titer (p .09) or 3 months negativization (p .8).ConclusionsThree months anti-PLA2R ab negativization seems to be a late predictor of remission, and lower serum albumin at diagnosis is an early marker for remission absence. Abbreviations: anti-P LA2R ab, anti-phospholipase A2 receptor antibody; eGFR, estimated glomerular filtration rate; ESKD, end stage kidney disease; MN, membranous nephropathy; NELL-1, neural epidermal growth factor-like 1 protein; RAAS: renin-angiotensin-aldosterone system; RBC: red blood cells; RRT, renal replacement therapy; T HSD7A, thrombospondin type-1 domain containing 7A.

Dataset Information

Antibody-Guided Therapy in Phospholipase A2 Receptor-Associated Membranous Nephropathy.

Introduction

Methods

Results

Conclusion

Publications

Antibody-Guided Therapy in Phospholipase A2 Receptor-Associated Membranous Nephropathy.

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