Anti–Phospholipase A2 Receptor Antibodies and Malignancy in Membranous Nephropathy

Timmermans, Sjoerd A.M.E.G.; Ayalon, Rivka; Paassen, Pieter van; Beck, Laurence H.; Rie, Henk van; Wirtz, Joris J. J. M.; Verseput, Gaico H.; Frenken, L.A.M.; Salant, David J.; Tervaert, Jan Willem Cohen

doi:10.1053/j.ajkd.2013.07.019

Cited by 57 publications

(40 citation statements)

References 10 publications

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“…Since the discovery of the transmembrane glycoprotein M-type phospholipase A 2 receptor (PLA 2 R), which was identified as the major target podocyte antigen involved in the majority of adult idiopathic MN cases [24], a distinction between idiopathic and secondary MN can be made more precisely by the detection of circulating antibodies against PLA 2 R. The patients with MN who have detectable anti-PLA 2 R are unlikely to have associated malignancy, whereas the absence of anti-PLA 2 R increases the risk of malignancy-associated MN and warrants careful searches for cancer [27]. Note that an anti-PLA 2 R autoantibody assay has not been approved by the US Food and Drug Administration at the time of this writing, although it is available in Europe [28].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Cancer in Membranous Nephropathy: A Systematic Review and Meta-Analysis of Observational Studies

Leeaphorn¹,

Kue-A-Pai²,

Thamcharoen³

et al. 2014

Am J Nephrol

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Background: The association between membranous nephropathy (MN) and cancer has been well documented. However, the true prevalence and characteristics of cancer associated with MN have not been well described. Methods: A systematic review and meta-analysis of cohort studies was conducted to summarize the prevalence of cancer-associated MN as well as patient characteristics and types of cancer in this population. We used a random-effects meta-analysis model to estimate the prevalence of cancer. Results: We included 6 studies (n = 785). The estimated prevalence of cancer was 10.0% (95% CI, 6.1-14.6). The mean age of MN patients with cancer was 67 ± 7 years. The diagnosis of cancer preceded the diagnosis of MN in 20 ± 6.8%. Lung cancer was the most common type of tumor, accounting for 22 cases (26%), followed by prostate cancer (13 cases, 15%), hematologic malignancies (12 cases, 14%), colorectal cancer (9 cases, 11%), breast cancer (6 cases, 7%), and stomach and esophageal cancer (5 cases, 6%). Conclusion: The estimated prevalence of cancer in patients with MN is 10% (95% CI, 6.1-14.6). The vast majority of tumors associated with MN are lung and prostate cancer. Hematologic malignancies should also be considered as one of the potential cancers associated with MN. Our study was based on a largely Caucasian population; therefore, the findings might not be applicable to other populations.

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Section: Discussionmentioning

confidence: 99%

Prevalence of Cancer in Membranous Nephropathy: A Systematic Review and Meta-Analysis of Observational Studies

Leeaphorn¹,

Kue-A-Pai²,

Thamcharoen³

et al. 2014

Am J Nephrol

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“…Consecutive patients who underwent renal biopsy between November 1979 and March 2011 in the province of Limburg, the Netherlands, were identified as having idiopathic MN [12] . Only those patients with idiopathic MN and either anti-PLA2R serum reactivity or glomerular PLA2R deposits, that is, patients with PLA2R-related MN, were included.…”

Section: Patient Cohortmentioning

confidence: 99%

“…Only those patients with idiopathic MN and either anti-PLA2R serum reactivity or glomerular PLA2R deposits, that is, patients with PLA2R-related MN, were included. Patients with secondary MN were excluded [12] . According to our Limburg Renal Registry protocol, renal biopsies were obtained as soon as it was feasible.…”

Section: Patient Cohortmentioning

confidence: 99%

Anti-PLA2R Antibodies as a Prognostic Factor in PLA2R-Related Membranous Nephropathy

Timmermans¹,

Hamid

Tervaert

et al. 2015

Am J Nephrol

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Background: The natural course of idiopathic membranous nephropathy (MN) varies, as it is known through favorable outcomes in most patients. However, one third of patients with idiopathic MN will slowly progress to end-stage renal disease (ESRD). To prevent disease progression, patients at high risk to develop ESRD are treated with immunosuppressive agents. Therefore, a correct selection of patients who need immunosuppressive treatment is important. Methods: Here, we evaluated the prognostic value of anti-phospholipase A2 receptor 1 antibody (anti-PLA2R) levels regarding clinical outcome in a well-defined cohort of 73 PLA2R-related MN patients with long-term follow-up. At baseline, patients were subdivided into patients with either low or high antibody levels based on ELISA testing. Results: Spontaneous remission rates were highest among patients with low anti-PLA2R levels (79%; hazard ratio 2.72 (95% CI 1.22-6.08), p = 0.02) after a median follow-up of 2.9 (95% CI 0.8-5.0, p < 0.001) years, whereas high anti-PLA2R levels were associated with persistent proteinuria (p = 0.04) and/or the need for immunosuppressive therapy (p < 0.001). Renal survival rates were 97% at 5 years, 93% at 10 years, and 89% at 15 years; however, this was not different between the anti-PLA2R groups. ESRD occurred significantly faster in patients with severe proteinuria as compared to patients with either mild (p = 0.02) or moderate proteinuria (p = 0.05). Conclusions: Low anti-PLA2R levels may predict spontaneous remissions in patients with PLA2R-related MN. Therefore, we suggest that quantification of anti-PLA2R is of value to monitor these patients.

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“…Idiopathic MN was diagnosed as described. 7 In addition, patients with secondary MN and nephrotic proteinuria from other underlying causes were included as a control cohort. We included all consecutive patients for whom baseline serum samples, obtained using similar processing and storage (-80°C) procedures at the time of renal biopsy, were available.…”

Section: Patient Populationmentioning

confidence: 99%

“…4,7 Briefly, human glomerular extracts or cellexpressed recombinant human PLA2R1 were electrophoresed under nonreducing conditions and transferred to nitrocellulose membranes. Membranes were blocked with 10% milk and incubated with human serum at a dilution of 1:25.…”

Section: Western Blotmentioning

confidence: 99%

Evaluation of Anti-PLA2R1 as Measured by a Novel ELISA in Patients With Idiopathic Membranous Nephropathy

Timmermans

Damoiseaux

Heerings-Rewinkel

et al. 2014

American Journal of Clinical Pathology

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Anti–Phospholipase A2 Receptor Antibodies and Malignancy in Membranous Nephropathy

Cited by 57 publications

References 10 publications

Prevalence of Cancer in Membranous Nephropathy: A Systematic Review and Meta-Analysis of Observational Studies

Prevalence of Cancer in Membranous Nephropathy: A Systematic Review and Meta-Analysis of Observational Studies

Anti-PLA2R Antibodies as a Prognostic Factor in PLA2R-Related Membranous Nephropathy

Evaluation of Anti-PLA2R1 as Measured by a Novel ELISA in Patients With Idiopathic Membranous Nephropathy

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