A ROC curve was used to determine the sensitivity and specificity of the assay, and p < 0.05 was considered as statistically significant. Medcalc 12.4.0 was used as statistical software.
RESULTS
The results of biopsies of the 53 patients evaluated are listed in Table I. Of these, 38 had histological diagnosis of membranous nephropathy and the remaining 15 patients had other glomerular diseases.
We did not find histological differences between idiopathic and secondary MN. The MN was idiopathic after clinical exclusion of secondary causes in 33 patients. The characteristics of iMN patients are listed in Table II.
Anti-PLA2R was positive in 57.6% (n = 19) of the 33 patients with iMN. All patients with secondary membranous nephropathy or other glomerular diseases did not show circulating anti-PLA2R (Table III).
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The sensitivity was 57.6% (CI 39.2-74.5) and specificity 100% (CI 47.8-100), AUC 0.788; p < 0.0001 for the detection of iMN (Fig. 1).
Ten (71.4%) of the 14 iMN patients with negative test for anti-PLA2R were already in treatment when the test was done and were in partial or complete remission of the disease (Table IV). In three patients the test was repeated and we observed that Anti-PLA2R became negative in two patients with iMN after treatment with cyclosporine and Anti-PLA2R became positive in one patient with relapse.
DISCUSSION
Anti-PLA2R in the studied population was only detected in the serum of patients with idiopathic MN and was negative in all patients with secondary MN or with other glomerular diseases. The high specificity of this test can help to make a diagnosis in patients with nephrotic syndrome/nephrotic proteinuria when a kidney biopsy is not performable. A positive test in these patients is highly suggestive of an idiopathic MN as the cause of the disease2,3.
]]> Our study demonstrated a low sensitivity for idiopathic MN diagnosis (57.5%). We think that this result was the consequence of some patients being already in treatment when the test was done. Some authors showed reduction of the antibody levels with treatment8,11. It seems that the treatment and the disease remission are associated to a negative test in patients with idiopathic MN proven by biopsy and a negative clinical evaluation.This test seems to be a useful predictor of iMN with a high diagnostic value for iMN at the active stage. Other studies also showed high specificity in predicting IMN (between 91% and 100%) and a lower sensitivity for both active and remission stages (between 47% and 69%)9-11,13. Three patients had successive determinations of Anti-PLA2R. This test became negative in two patients with iMN after treatment with cyclosporine. Anti-PLA2R became positive in one patient with relapse. The usefulness of this assay as a treatment response marker should be evaluated.
All patients with sMN tested negative. The test proved consistently negative in patients with lupus nephritis12.
These findings strongly suggest that lupus MN is not related to PLA2R. All in all, large-cohort prospective studies are required, integrating the degree of proteinuria, immunosuppressive treatment, time of observation, repetitive measurements of anti-PLA2R levels and glomerular immune deposits of anti-PLA2R13,14.
References
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]]>9. Behnert A, Fritzler MJ, Teng B, et al. An anti-phospholipase A2 receptor quantitative immunoassay and epitope analysis in membranous nephropathy reveals different antigenic domains of the receptor. PLoS One 2013;8(4):e61669. [ Links ]
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11. Oh YJ, Yang SH, Kim DK, Kang SW, Kim YS Autoantibodies against phospholipase A2 receptor in Korean patients with membranous nephropathy. PLoS One 2013;8(4):e62151. [ Links ]
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13. Hu SL, Wang D, Gou WJ, Lei QF, Ma TA, Cheng JZ. Diagnostic value of phopholipase A2 receptor in idiopathic membranous nephropathy: a systematic review and metaanalysis. J Nephrol 2014;27(2):111-116. [ Links ]
]]>14. Hofstra JM, Wetzels JF. Anti-PLA2R antibodies in membranous nephropathy: ready for routine clinical practice? Neth J Med 2012;70(3):109-113. [ Links ]
Drª Guida Menezes
Nephrology Department, Hospital de Curry Cabral. Centro Hospitalar de Lisboa Central
Rua Beneficência 8, 1069-166 Lisbon, Portugal.
E-mail: guidameneses@gmail.com
Conflict of interest statement: None declared ]]>
Received for publication: 20/08/2014
Accepted in revised form: 03/11/2014
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