De Novo Membranous Glomerulonephritis



De Novo Membranous Glomerulonephritis


Anthony Chang, MD





Key Facts


Clinical Issues



  • 0.5-9% of kidney transplant patients


  • Proteinuria


  • Renal dysfunction


  • Unfavorable prognosis



    • 2/3 of patients eventually require renal replacement therapy


Microscopic Pathology



  • Glomerular basement membrane thickening, diffuse or segmental



    • GBM “spike” formation


  • Granular IgG staining in glomerular capillary walls



    • C4d and C3 may also stain glomerular capillaries in similar pattern


    • Careful evaluation of C4d glomerular staining pattern is critical if this is only antibody tested in transplant kidney biopsies


    • C4d in peritubular capillaries found in ˜ 70% of cases


  • Subepithelial electron-dense deposits seen by electron microscopy ± basement membrane “spike” formation


  • Mesangial hypercellularity in 1/3 of cases


  • Spikes of GBM on silver or PAS stains, ± “Swiss cheese” appearance depending on stage of MGN


Ancillary Tests



  • IgG1 is predominant or codominant subclass


Top Differential Diagnoses



  • Recurrent MGN


  • Chronic transplant glomerulopathy






Periodic acid-Schiff shows thickening of the glomerular basement membranes image and focal mild mesangial hypercellularity image.






Jones methenamine silver shows a hint of subepithelial “spike” formation image along some of the glomerular basement membranes.


TERMINOLOGY


Abbreviations



  • Membranous glomerulonephritis (MGN)


Synonyms



  • Membranous glomerulopathy, de novo


  • Membranous nephropathy, de novo


  • Membranous glomerulonephropathy, de novo



Definitions



  • MGN in kidney allograft when primary cause of end-stage renal disease is not MGN


ETIOLOGY/PATHOGENESIS


Allo-/Autoantibody



  • May represent unusual manifestation of chronic antibody-mediated rejection


  • Can occur in HLA identical grafts, presumably due to non-HLA antigen



    • Rat model of de novo MGN occurs only in transplant and not native kidney


    • One autopsy showed de novo MGN involving only kidney allograft without MGN in native kidneys


  • One de novo MGN case with donor-specific antibodies against HLA-DQ7


  • Association with C4d deposition in peritubular capillaries and anti-HLA-DQ


  • No autoantibodies to phospholipase A2 receptor (PLA2R)


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 0.5-9% of kidney transplant patients


Presentation



  • Typically manifests late (> 3 years)


  • Renal dysfunction


  • Proteinuria



    • 2nd most common cause of proteinuria in renal allograft patients


    • Often nephrotic range (> 3 g/24 hours), may be intermittent or persistent


Treatment



  • Not well defined


Prognosis



  • Unfavorable



    • 5-year graft loss of 50% or more


    • 2/3 eventually progress to renal failure


  • De novo MGN may recur in subsequent renal allografts


MACROSCOPIC FEATURES


General Features



  • Renal vein thrombosis occasionally present



    • Less common than with idiopathic MGN in native kidneys


MICROSCOPIC PATHOLOGY


Histologic Features



  • GBM thickening



    • Focal &/or segmental thickening common


  • Glomerular capillaritis in ˜ 50%



    • Increased leukocytes within glomerular capillaries


  • Mesangial hypercellularity in ˜ 33%


  • Double contours or duplication of GBM in 50%



    • Possibly due to concurrent chronic transplant glomerulopathy (chronic antibody-mediated rejection)



  • Prominent interstitial inflammation



    • Often sufficient for diagnosis of acute (T-cell-mediated) rejection


  • Intimal arteritis



    • Acute (type 2) rejection found in subset


ANCILLARY TESTS


Immunofluorescence



  • Positive granular capillary wall staining for IgG, kappa and lambda light chains



    • IgG1 is predominant or codominant subclass



      • IgG4 is predominant subclass in primary (or recurrent) MGN


    • Variable capillary wall staining for C4d, C3, C1q, and IgM


  • C4d(+) peritubular capillary deposition in ˜ 70%


Electron Microscopy



  • Transmission



    • Subepithelial amorphous electron-dense deposits



      • Often small and relatively sparse


      • Stage I (Ehrenreich-Churg) deposits common


    • Duplication of GBMs



      • Subendothelial space widening when injured endothelial cells detach from GBM


DIFFERENTIAL DIAGNOSIS


Recurrent MGN



  • Clinical history of MGN as original disease


  • Earlier onset (< 3 months)


  • Autoantibodies to PLA2R


  • IgG4 predominant


Donor-Derived MGN



  • Present in donor biopsy, disappears in a few months


Chronic Transplant Glomerulopathy

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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on De Novo Membranous Glomerulonephritis

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