Mechanisms of Primary Membranous Nephropathy.

ABSTRACT

Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus and one of the leading causes of nephrotic syndrome. The disease exhibits heterogenous outcomes with approximately 30% of cases progressing to end-stage renal disease. The clinical management of MN has steadily advanced owing to the identification of autoantibodies to the phospholipase A2 receptor (PLA2R) in 2009 and thrombospondin domain-containing 7A (THSD7A) in 2014 on the podocyte surface. Approximately 50-80% and 3-5% of primary MN (PMN) cases are associated with either anti-PLA2R or anti-THSD7A antibodies, respectively. The presence of these autoantibodies is used for MN diagnosis; antibody levels correlate with disease severity and possess significant biomarker values in monitoring disease progression and treatment response. Importantly, both autoantibodies are causative to MN. Additionally, evidence is emerging that NELL-1 is associated with 5-10% of PMN cases that are PLA2R- and THSD7A-negative, which moves us one step closer to mapping out the full spectrum of PMN antigens. Recent developments suggest exostosin 1 (EXT1), EXT2, NELL-1, and contactin 1 (CNTN1) are associated with MN. Genetic factors and other mechanisms are in place to regulate these factors and may contribute to MN pathogenesis. This review will discuss recent developments over the past 5 years.