A conceptual framework linking immunology, pathology, and clinical features in primary membranous nephropathy.

Abstract

Primary membranous nephropathy (PMN) is a leading cause of adult nephrotic syndrome. The field took a major step forward with the identification of phospholipase A2 receptor (PLA2R) as target antigen in the majority of cases and with the ability to measure circulating autoantibodies to this protein (aPLA2R). Since then, the existence of additional target antigens such as thrombospondin type-1 domain containing 7A, exostosin 1 and 2, NELL-1, Semaphorin-3B has been demonstrated. The ability to detect and monitor levels of circulating autoantibodies has opened a new window onto the humoral aspect of PMN. Clinicians now rely on clinical parameters such as proteinuria, as well as levels of circulating aPLA2R and the results of immunofluorescent staining for aPLA2R on renal biopsy, to guide the management of this disease. The relationship between immunologic and clinical disease course is consistent, but not necessarily intuitive. In addition, kidney biopsy provides only a single snapshot of disease that needs to be interpreted in light of changing clinical and serological findings. A clear understanding of these dynamic parameters is essential for staging, treatment, and management of this disease. This review aims to shed light on current knowledge regarding the development and time-course of changes in serum aPLA2R levels, proteinuria and histological findings that underlie the pathophysiology of PMN.