Membranous as antibodies bind to a membrane-based antigen and

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in
non-diabetic adults(1).
It usually occurs as idiopathic disease (primary MN) due to kidney-limited
autoimmune disorder(2).  It’s
characterized by glomerular basement membrane thickening without prominent
hypercellularity, and the presence of Subepithelial electron-dense deposits(3).

 

 

 A large percentage of
membranous nephropathy cases are, however, secondary to systemic autoimmune
diseases such as  SLE, infections and the
use of certain drugs (NSAIDs)(2).

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The mechanism by which the Subepithelial deposits form in secondary MN
is not very clear and may be explained by the deposition of circulating immune
complexes in the Subepithelial space(2).

 

Myasthenia gravis is a rare cause of nephropathy(4). In some cases of nephrotic
syndrome, the mechanism is an imbalance between T helper cells class 1 and 2(5). In myasthenia gravis, T cell dysfunction leads to the production of
lymphokine, which increases the permeability of glomerular basement membrane(6). Evidence
supporting the association between nephropathy and thymic disease (thymoma,
thymic hyperplasia, and Myasthenia gravis) is growing, in which minimal change
disease 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 and
some of the treatments for idiopathic MN are potentially toxic to the kidney(1).

 

Differentiating idiopathic
MN from secondary MN, especially in elderly patients in whom malignancies tend
to 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), a
185 kDa type I transmembrane glycoprotein expressed on glomerular podocytes is the main target
of autoantibodies in idiopathic MN(13). Subepithelial deposits form as
antibodies bind to a membrane-based antigen and complement(1)(2).

 

The finding of mesangial
deposits in our case raised the possibility of a secondary form of MN.  the
specimen obtained from the renal biopsy was sent for PLA2R immunofluorescence
testing to differentiate primary from secondary MN and the result came back
negative which raised the possibility of malignant relapse or systemic
autoimmune disorder (SLE)

 

Since the
patient had no systemic manifestations of active SLE like joint pain, rash,
oral ulcers and fever and the repeat ANA, anti-dsDNA were negative, the
probability of lupus nephritis grade V was eliminated.

Given her
LAP on PET-CT scan, concerns of relapsing malignancy were raised and cancer
surveillance testing was needed which included biopsy of the FDG-avid L.N,
mammography, colonoscopy and bone marrow aspiration.

In our case
the patient was started on prednisone and then switched to ACTHAR® (with a plan
of 6-12 months of treatment) since steroids alone
are not affective and Acthar® has been studied and was considered a safer
alternative to calcineurin inhibitors and alkylating agents with reasonable
efficacy in the treatment of membranous nephropathy.

Longer treatment course of ACTHAR® is
hoped to induce remission with less risk than CNI+ steroids, Rituxan and
certainly alkylating agents, unless renal function deteriorates acutely or
proteinuria worsens steadily then Rituxan would be considered.

The benefit of therapy using steroids and
immunosuppressants suggests that membranous nephropathy is related to the
disordered immune system(4).

Thymectomy, which is a standard therapy for myasthenia
gravis, is still considered as an option for treatment.
Thymectomy can
be followed by numerous changes in lymphocyte
functions which may require several years to be revealed(14), suggesting that careful long-term follow-up
for is necessary.