A collaboration between UAMS Nephrology and nephropathologists at Arkana Laboratories has greatly expanded our understanding of the causes of membranous nephropathy. Membranous nephropathy occurs when antibodies against podocyte proteins or circulating antigens are deposited along the glomerular basement membrane and lead to increased glomerular permeability to albumin and other proteins. Until recently, only a few of the causative antigens in membranous were known, with PLA2R being the most prevalent. Over the last three years, a collaboration between UAMS and Arkana has identified several new antigen targets in both primary membranous nephropathy and membranous nephropathy secondary to lupus nephritis.
Investigators at Arkana identify cases of membranous nephropathy in which the causative antibody is unknown. They process kidney tissue specimens, either by isolating antibodies in the tissue and the proteins the antibodies are bound to, or by cutting out the glomeruli with a laser capture microscope. The samples are then sent to UAMS for analysis of the proteins present in the sample using mass spectrometry. These studies have contributed to identification of the proteins transforming growth factor beta receptor 3 (TGFBR3), neural cell adhesion molecule 1 (NCAM1), serine protease HTRA1, and serum amyloid P (SAP) as target antigens in membranous or membranous-like nephropathies. The group is currently looking into ways to make this technique more useful in the diagnosis of membranous nephropathy. Overall, these studies have increased our understanding of mechanisms causing membranous nephropathy and will lead to better diagnosis and treatment of patients with these diseases.