Secondary Membranous Nephropathy. A Narrative Review

Abstract

Membranous nephropathy (MN) is a common cause of proteinuria and nephrotic syndrome all over the world. It can be subdivided into primary and secondary forms. Primary form is an autoimmune disease clinically characterized by nephrotic syndrome and slow progression. It accounts for ~70% cases of MN. In the remaining cases MN may be secondary to well-defined causes, including infections, drugs, cancer, or autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), urticarial vasculitis, sarcoidosis, thyroiditis, Sjogren syndrome, systemic sclerosis, or ankylosing spondylitis. The clinical presentation is similar in primary and secondary MN. However, the outcome may be different, being often related to that of the original disease in secondary MN. Also, the treatment may be different, being targeted to the etiologic cause in secondary MN. Thus, the differential diagnosis between primary and secondary MN is critical and should be based not only on history and clinical features of the patient but also on immunofluorescence and electron microscopy analysis of renal biopsy as well as on the research of circulating antibodies. The identification of the pathologic events underlying a secondary MN is of paramount importance, since the eradication of the etiologic factors may be followed by remission or definitive cure of MN. In this review we report the main diseases and drugs responsible of secondary MN, the outcome and the pathogenesis of renal disease in different settings and the possible treatments.

Case Report: A Rare Presentation of NSAID-Induced Secondary Membranous Nephropathy in a Pediatric Patient

“…The exact mechanism of NSAID-induced secondary MN is unknown. Different theories have been proposed, including COX inhibition, glomerular deposition of antigens that bind to NSAIDs, or NSAIDs triggering autoimmune reaction against antigens in the glomerular filtration barrier (2,10).…”

“…The duration of NSAID treatment prior to the development of MN is highly variable, from a few weeks to a few months, but there is a rapid development of nephrotic-range proteinuria or presentation with nephrotic syndrome at disease onset (2). Because the symptoms of hypoalbuminemia and edema may be more apparent in NSAID-induced MN, an early renal biopsy is often performed, and this also explains the early stage of MN (stage I or II) often seen on renal biopsies in these patients (2). Our patient also had stage I-II MN on renal biopsy.…”

“…Our patient stopped using NSAIDs after the initial presentation. She was also initially started on steroids (prednisone) because of her presentation with nephrotic syndrome and based on the (2,6). We initiated treatment with an ACE inhibitor and monitored the improvement in proteinuria.…”

“…Primary MN is a renalspecific autoimmune glomerular disease characterized by proteinuria, primarily mediated by antibodies against phospholipase A2 receptor (PLA2R). It is characterized by specific histological findings on renal biopsy, such as a pathognomic "spike pattern" of the glomerular basement membrane on light microscopy (LM); positive PLA2R immunostaining, IgG and complement C3 distributed in a delicate granular pattern distributed across a subepithelial portion of glomeruli on immunofluorescence microscopy (IFM); and electron-dense deposits confined to the subepithelial space on electron microscopy (EM), with the absence of mesangial deposits (2,3). Secondary MN has previously been shown to be caused by viral infections (e.g., Hepatitis B, Hepatitis C, or HIV), autoimmune conditions (e.g., lupus), drugs (e.g., penicillamine, gold, or NSAIDs), hematological malignancies, and solid organ tumors (1, 2).…”

“…Secondary MN has previously been shown to be caused by viral infections (e.g., Hepatitis B, Hepatitis C, or HIV), autoimmune conditions (e.g., lupus), drugs (e.g., penicillamine, gold, or NSAIDs), hematological malignancies, and solid organ tumors (1, 2). The histological findings of secondary MN can vary depending on the cause, and PLA2R immunostaining is negative (2). Primary MN is a more common form of MN in adults in the literature review, comprising ∼80% of total MN cases, but secondary MN may be more common in children (1).…”