Kidney Biopsy Is Required for Nephrotic Syndrome with PLA2R+ and Normal Kidney Function: The Con View.

Abstract

The main obstacle to medical progress is dogma.—Gabriel Richet Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adult patients of European decent (1,2). This morphologic pattern of injury is characterized by thickening of the glomerular capillary wall on light microscopy, presence of Igs (usually IgG and C3) deposition along the capillary walls on immunofluorescence microscopy, and subepithelial deposits along the glomerular basement membrane on electron microscopy (EM) (3). Primary MN, responsible for approximately 80% of cases, is a renal-limited autoimmune disease caused by circulating antibodies targeting antigens on the surface of the podocyte (4). The target antigen has been identified as the M-type phospholipase A2 receptor 1 (PLA2R) in 70%–80%, the thrombospondin type-1 domain containing 7A (THSD7A) in 1%–5%, and the recently described neural EGF-like 1 protein (NELL-1) in 5%–10% of cases (5⇓–7). In approximately 20% of patients, MN is secondary to infections (hepatitis B), systemic autoimmune diseases (SLE), drugs (nonsteroidal anti-inflammatory drugs), or malignancy (8). Traditionally, the gold standard for diagnosis of MN has been a kidney biopsy. However, the recent availability of assays for PLA2R has revolutionized the way we approach MN. There are two validated and commercially available assays for anti-PLA2R antibody: one is an ELISA, which provides a quantitative antibody titer and is 66.9% sensitive and 99.6% specific, and the other is a semiquantitative immunofluorescence assay test (IFA), which is 77.1% sensitive and 100% specific reported as positive, indeterminate, or negative. A large body of evidence supports a central role for serology in diagnosis and management of MN. The evidence is most explicit for PLA2R-associated MN, as this is the most common and longest recognized form. To start, the specificity of anti-PLA2R antibodies for a diagnosis of MN is close to 100% (9). Positive anti-PLA2R …