Diagnostic role of renal biopsy in PLA2R1-antibody-positive patients with nephrotic syndrome

Renal biopsy is the gold standard for diagnosis of membranous nephropathy. Circulating PLA2R1 antibody found in 75% of patients with membranous nephropathy is very specific for the diagnosis of this disease. Therefore, the question arises whether PLA2R1-antibody-positive patients still need a diagnostic renal biopsy. In this study we investigated whether additional relevant information is obtained by performing renal biopsy in nephrotic patients, who are PLA2R1-antibody positive. A detailed analysis of renal biopsies, including immunohistochemistry and electron microscopy, was performed in 263 patients with biopsy-proven membranous nephropathy, of whom 194 patients were PLA2R1-antibody positive, to detect diagnostic features additional to membranous nephropathy. Twelve (6%) of the 194 PLA2R1-antibody-positive patients had a second relevant diagnosis in addition to membranous nephropathy: five (3%) patients had interstitial nephritis, in five (3%) other patients a diabetic nephropathy was diagnosed and two (1%) patients had IgA nephropathy. Patients with a second diagnosis in addition to membranous nephropathy had a significantly higher serum creatinine (p < 0.01) and lower eGFR (p = 0.04) compared to patients in whom only the diagnosis of membranous nephropathy was made. In 7 (10%) of 69 PLA2R1-antibody-negative patients, renal biopsies showed an additional diagnosis to membranous nephropathy: one (1%) case of IgA nephropathy, cholesterol emboli, IgG4-related disease, necrotising glomerulonephritis, thrombotic microangiopathy, interstitial nephritis and diabetic nephropathy each. The advantage of detecting an additional diagnosis to membranous nephropathy in 6% of PLA2R1-antibody-positive patients by renal biopsy has to be balanced to the potential risks and costs of the biopsy procedure. Renal biopsy is particularly relevant in patients presenting with impaired renal function and abnormalities in urinalysis going beyond proteinuria. Immunohistochemical staining for PLA2R1 was the only histomorphologic analysis allowing a reliable differentiation of PLA2R1-antibody-positive from PLA2R1-antibody-negative membranous nephropathy.