Primary Membranous Glomerulonephritis: The Role of Serum and Urine Biomarkers in Patient Management

Abstract

The detection of phospholipase A2 receptor (PLA₂R) and thrombospondin domain containing 7A THSD7A among primary membranous glomerulonephritis (MGN) patients transformed the diagnosis, treatment monitoring, and prognosis. Anti-PLA₂R can be detected in 70-90% of primary MGN patients while anti-THSD7A in 2-3% of anti-PLA₂R negative primary MGN patients depending on the technique used. Serum and urine samples are less invasive and non-invasive, respectively, and thus can detect the presence of anti-PLA₂R and anti-THSD7A with higher sensitivity and specificity, which is significant in patient monitoring and prognosis. It is better than exposing patients to a frequent biopsy, which is an invasive procedure. Different techniques of detection of PLA₂R and THSD7A in patients' urine and sera were reviewed to provide newer and alternative techniques. We proposed the use of biomarkers (PLA₂R and THSD7A) in the diagnosis, treatment decision, and follow-up of patients with primary MGN. In addition, other prognostic renal biomarkers like retinol binding protein (RBP) and beta-2 microglobulin were reviewed to detect the progression of renal damage for early intervention.

Keywords: M-type phospholipase A2; beta-2 microglobulin; membranous glomerulonephritis; neutral endopeptidase; retinol binding protein; thrombospondin type containing domain A7.

Figure 1

Combined image: Mechanism of anti-podocyte (anti-neutral endopeptidase (NEP), anti-phospholipase A2 receptor (PLA₂R), anti-thrombospondin domain containing 7A (THSD7A)) antibody-mediated disease in membranous glomerulonephritis (MGN), part of glomerular basement membrane (GBM). Formation of complexes: (A) Antigen–antibody reacts to form complexes at the podocyte. (B) Complement activation system via the classical and alternative pathway. (C) Formation of complement membrane attack complex leading to cell injury. (D) Podocyte injury leading to proteinuria and cell death.