New Ways of Understanding Membranous Nephropathy

Abstract

Background: In the last decade, great advances have been made in the field of membranous nephropathy (MN). The autoimmune nature of the disease has been confirmed with the description of diverse antigens, and few but very important prospective trials regarding treatment alternatives have been published, changing profoundly the way we understand this entity. Nowadays, an individualized therapeutic scheme based on clinical and serologic data appears to be the most appropriate method to manage patients with MN. Although there is still a long way to go, it is expected that future scientific progress will enable a patient-centered medicine based on concept-driven therapies. Summary: MN is the most common cause of nephrotic syndrome (NS) in white adults. Approximately one-third of patients achieve spontaneous remission, one-third remain stable, and onethird have an aggressive course with persistent NS and deterioration of renal function. About 80% of patients have circulating autoantibodies to phospholipase A2 receptor 1. Numerous therapies have been described including alkylating agents, rituximab, and calcineurin inhibitors, but new drugs are currently being explored. Here, we review the most important aspects regarding MN with an emphasis on results of the most recent clinical trials and pathophysiologic advances. Key Messages: 1. Evolving pathophysiologic concepts and recently published clinical trials have deeply changed our view of MN. 2. Most patients with MN present autoantibodies against diverse glomerular antigens. 3. Currently, an individual patient-centered management based on clinical and serologic markers is the most adequate approach to treat patients with MN.

Membranous Nephropathy Associated With Indigenous Indian Medications Containing Heavy Metals

“…Primary MN is an immune-mediated disease, mediated by autoantibodies directed against phospholipase A 2 receptor antigen, thrombospondin type 1 domain-containing 7A, and neural epidermal growth factor-like 1 protein. 1 However, MN can also be caused by a variety of secondary origins, including but not limited to, autoimmune diseases, malignancies, infections, and exposure to drugs and heavy metals, including gold and mercury. Exposure to mercury is rare in the general population; it usually occurs in the context of long-term occupational exposure.…”

“…About 80% of MN cases are primary, whereas the rest result from multiple secondary causes. 1 In the early days of modern medicine, mercurial organic compounds were used as diuretics, laxatives, and anti-infective agents. The use of mercury as a pharmacologic agent was abandoned by modern medicine owing to the toxic effects.…”

<p>Clusterin Deficiency Predisposes C57BL/6j Mice to Cationic Bovine Serum Albumin-Induced Glomerular Inflammation</p>

“…[4][5][6][7][8] Except of similar clinical features such as proteinuria, MN is classified into primary and secondary MN based on the different profiles of histopathology. 9 The primary MN is typically caused by the binding of circulating autoantibodies to podocyte-expressing autoantigens such as M-type phospholipase A2 receptor (PLA2R) to form immunecomplex deposit in the subepithelial zone between the basement membrane and the podocyte, and subsequent thickening of glomerular basement membrane (GBM), a typical lesion of MN. 7,[9][10][11] The secondary MN is associated with circulating antigens or pre-formed circulating immune complexes (CIC) that may be generated by the systemic diseases (eg, systemic lupus erythematosus, SLE), malignancy, medications, infections or exposure to foreign antigens.…”

“…9 The primary MN is typically caused by the binding of circulating autoantibodies to podocyte-expressing autoantigens such as M-type phospholipase A2 receptor (PLA2R) to form immunecomplex deposit in the subepithelial zone between the basement membrane and the podocyte, and subsequent thickening of glomerular basement membrane (GBM), a typical lesion of MN. 7,[9][10][11] The secondary MN is associated with circulating antigens or pre-formed circulating immune complexes (CIC) that may be generated by the systemic diseases (eg, systemic lupus erythematosus, SLE), malignancy, medications, infections or exposure to foreign antigens. 9,10 In the secondary MN, the antigens bound with antibodies or CIC accumulate not only in the subepithelial space but also likely in the subendothelial space and the mesangium, resulting in atypical lesions including mesangial expansion.…”

“…7,[9][10][11] The secondary MN is associated with circulating antigens or pre-formed circulating immune complexes (CIC) that may be generated by the systemic diseases (eg, systemic lupus erythematosus, SLE), malignancy, medications, infections or exposure to foreign antigens. 9,10 In the secondary MN, the antigens bound with antibodies or CIC accumulate not only in the subepithelial space but also likely in the subendothelial space and the mesangium, resulting in atypical lesions including mesangial expansion. 7,10 However, the molecular mechanisms by which the immune complexes or autoantibody or CIC-stimulated inflammation cause glomerular injury and proteinuria in MN are not fully understood.…”