The optimal anti-phospholipase A2 receptor cutoff for the diagnosis of idiopathic membranous nephropathy: a single-center retrospective study

Abstract

Background/aims: Anti-phospholipase A2 receptor (PLA2R) autoantibody is the main biomarker of idiopathic membranous nephropathy (IMN). We aimed to find a new cutoff value of anti-PLA2R for patients with IMN and to explore the relevance between this antibody and baseline clinical parameters.

Methods: A total of 670 subjects including 374 IMN cases and 296 non-IMN controls were included between January 2017 and January 2020. All clinical parameters were collected at the time of renal biopsy. The levels of anti-PLA2R were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit. The optimal cutoff value was calculated by a receiver operating characteristic curve and compared in diagnostic efficiency.

Results: The optimal cutoff value of anti-PLA2R for IMN was 7.45 RU/mL with the highest Youden index, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 80.75%, 97.97%, 98.05% and 80.11%, respectively. Anti-PLA2R levels in IMN patients demonstrated a significant positive correlation with serum creatinine and 24-hour urinary protein, while they showed a negative correlation with serum albumin and estimated glomerular filtration rate.

Conclusion: The recommended cutoff value of anti-PLA2R is 7.45 RU/mL using ELISA detection for distinguishing IMN from non-IMN nephropathy. The level of anti-PLA2R is related to baseline renal function in IMN. This new threshold can improve the diagnostic efficiency and facilitate early diagnosis of IMN.

Keywords: Cutoff value; Enzyme-linked immunosorbent assay; Membranous glomerulonephritis; Phospholipase A2 receptors; Receiver operating characteristic curve.

Figure 1

The process of patients screening and classification. IMN, idiopathic membranous nephropathy; SMN, secondary membranous nephropathy; IgAN, IgA nephropathy; FSGS, focal and segmental glomerulosclerosis; MCD, minimal change disease; DN, diabetic nephropathy; LN, lupus nephritis; HBV-GN, HBV-associated glomerulonephritis; ANA, antinuclear antibodies; SSA, Sjögren’s syndrome-A; SSB, Sjögren’s syndrome-B; ANCA, antineutrophil cytoplasmic antibodies; MPO, myeloperoxidase; APL, antiphospholipid antibodies; GBM, glomerular basement membrane; TPO, thyroid peroxidase; TG, thyroglobulin; TR, thyrotropin receptor; CEA, carcinoembryonic antigen; AFP, alpha-fetoprotein; CA, carbohydrate antigen; PSA, prostate specific antigen; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; anti-HBc, anti-hepatitis B core antibodies; HCV, hepatitis virus C; HIV, human immunodeficiency virus; SM, Smith; CT, computed tomography.

Figure 2

The distribution of anti-phospholipase A2 receptor antibody (anti-PLA2R) levels (log-transformed) in different nephropathies. In the idiopathic membranous nephropathy (IMN), the upper and lower short line show the 75th and 25th percentiles respectively and the middle long line shows the median. In the minimal change disease (MCD), diabetic nephropathy (DN), and lupus nephritis (LN), the upper short lines show 75 percentiles and the median (long) lines and 25 percentiles (short) lines coincide with each other. In the IgA nephropathy (IgAN), focal and segmental glomerulosclerosis (FSGS), hepatitis B virus-associated glomerulonephritis (HBV-GN), and Others, the three lines showing the 25th, 50th and 75th percentiles are all at the same level. The subgroups of Other include patients with hypertensive renal damage, interstitial nephritis, plasmacytoma-associated nephropathy, primary renal amyloidosis, purpura nephritis, membranoproliferative glomerulonephritis, endocapillary proliferative glomerulonephritis, C3 glomerulonephritis, acute tubular necrosis and mild glomerular ischemia with chronic interstitial fibrosis.

Figure 3

Correlations between the levels of anti-phospholipase A2 receptor antibody (anti-PLA2R; log-transformed) and clinical parameters in the idiopathic membranous nephropathy. eGFR, estimated glomerular filtration rate.

Figure 4

Receiver operating characteristic curve of anti-phospholipase A2 receptor antibody (anti-PLA2R) in the diagnosis of idiopathic membranous nephropathy. AUC, area under receiver operating characteristic curve; CI, confidence interval.