Membranous nephropathy (MN) is a common cause of nephrotic syndrome innon-diabetic adults(1).It usually occurs as idiopathic disease (primary MN) due to kidney-limitedautoimmune disorder(2). It’scharacterized by glomerular basement membrane thickening without prominenthypercellularity, and the presence of Subepithelial electron-dense deposits(3). A large percentage ofmembranous nephropathy cases are, however, secondary to systemic autoimmunediseases such as SLE, infections and theuse of certain drugs (NSAIDs)(2). The mechanism by which the Subepithelial deposits form in secondary MNis not very clear and may be explained by the deposition of circulating immunecomplexes in the Subepithelial space(2). Myasthenia gravis is a rare cause of nephropathy(4).
In some cases of nephroticsyndrome, the mechanism is an imbalance between T helper cells class 1 and 2(5). In myasthenia gravis, T cell dysfunction leads to the production oflymphokine, which increases the permeability of glomerular basement membrane(6). Evidencesupporting the association between nephropathy and thymic disease (thymoma,thymic hyperplasia, and Myasthenia gravis) is growing, in which minimal changedisease is being the most common among other nephropathies(7–10). Clinically,distinguishing between primary and secondary MN is of absolute importance,since therapy in the secondary MN must be directed at the underlying cause andsome of the treatments for idiopathic MN are potentially toxic to the kidney(1). Differentiating idiopathicMN from secondary MN, especially in elderly patients in whom malignancies tendto occur, necessitates the need for an accurate biomarker to use for differentiation(11)(12). Studies have showed that the M-type phospholipase A2 receptor (PLA2R), a185 kDa type I transmembrane glycoprotein expressed on glomerular podocytes is the main targetof autoantibodies in idiopathic MN(13). Subepithelial deposits form asantibodies bind to a membrane-based antigen and complement(1)(2).
The finding of mesangialdeposits in our case raised the possibility of a secondary form of MN. thespecimen obtained from the renal biopsy was sent for PLA2R immunofluorescencetesting to differentiate primary from secondary MN and the result came backnegative which raised the possibility of malignant relapse or systemicautoimmune disorder (SLE) Since thepatient had no systemic manifestations of active SLE like joint pain, rash,oral ulcers and fever and the repeat ANA, anti-dsDNA were negative, theprobability of lupus nephritis grade V was eliminated.Given herLAP on PET-CT scan, concerns of relapsing malignancy were raised and cancersurveillance testing was needed which included biopsy of the FDG-avid L.
N,mammography, colonoscopy and bone marrow aspiration.In our casethe patient was started on prednisone and then switched to ACTHAR® (with a planof 6-12 months of treatment) since steroids aloneare not affective and Acthar® has been studied and was considered a saferalternative to calcineurin inhibitors and alkylating agents with reasonableefficacy in the treatment of membranous nephropathy.Longer treatment course of ACTHAR® ishoped to induce remission with less risk than CNI+ steroids, Rituxan andcertainly alkylating agents, unless renal function deteriorates acutely orproteinuria worsens steadily then Rituxan would be considered.The benefit of therapy using steroids andimmunosuppressants suggests that membranous nephropathy is related to thedisordered immune system(4).Thymectomy, which is a standard therapy for myastheniagravis, is still considered as an option for treatment.Thymectomy canbe followed by numerous changes in lymphocytefunctions which may require several years to be revealed(14), suggesting that careful long-term follow-upfor is necessary.
