A Case of Nephrotic-Range Proteinuria and False-Positive Anti-phospholipase A2 Receptor (PLA2R) Antibodies

Introduction: Autoantibodies to the M-type phospholipase A2 receptor (anti-PLA2R AB) have been demonstrated to be highly specific for the diagnosis of primary membranous nephropathy (MN). We present a case of anti-PLA2R AB positivity with no membranous glomerular pathology. Case Description: A 45-year-old Malay female was referred for the evaluation of nephrotic-range proteinuria and elevated serum creatinine (sCr). She was admitted for uncontrolled hypertension and acute decompensated heart failure with reduced ejection fraction. She did not have diabetes mellitus. On admission, sCr was 147 umol/L (eGFR 37 ml/min/1.73m2), serum albumin 42 g/L, urine albumin/creatinine ratio (uACR) 361.1 mg/mmol, protein/creatinine ratio 4 g/g and minimal hematuria (5 cells/uL). 24-hour total urine protein was 0.57 g/d on a suboptimal collection. Serological testing revealed faintly positive antinuclear antibody titer (1:160, homogeneous pattern) and positive anti-PLA2R AB 49.6 RU/ml (IgG ELISA Euroimmun). She was started on goal-directed therapy for heart failure. Serial repeated measurements of anti-PLA2R AB remained elevated over the next 5 months (49.6, 68.46 RU/ml) with persistent proteinuria. A kidney biopsy was obtained, revealing focal segmental glomerular sclerosis, arteriolar hyalinosis and focal arteriolar thrombosis, without features of MN. Immunofluorescence was weakly positive (1-2+) for IgM and C3 along glomerular capillary walls but negative for IgG. Electron microscopy showed mild basement membrane thickening, moderately extensive podocyte foot effacement (30-40% capillary wall surface area), but no subepithelial electron dense deposits were found. The diagnosis of hypertensive nephropathy with thrombotic microangiopathy (TMA) and FSGS was made. Her dose of valsartan was optimized and dapagliflozin was added. Over the next year, her sCr was stable at 151 umol/L (eGFR 36 ml/min/1.73 m2) and uACR regressed to 39.8 mg/mmol. Discussion: The specificity of anti-PLA2R AB for MN has been described to be as close to 100%, allowing patients with nephrotic syndrome and positive serology to forego biopsy. Other cases of anti-PLA2R AB positivity without MN have described minor glomerular, FSGS or diabetic nephropathy changes but not TMA. Our case adds to the body of literature of false-positive anti-PLA2R AB and supports pursuing a kidney biopsy especially when nephrotic syndrome is absent.