8 4 09 Johnson Membranous Nephropathy

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http://www.dcss.cs.amedd.army.mil/field/FLIP%20Disk%2041/FLIP.html
      Idiopathic
Membranous Nephropathy
       Paul M. Johnson
     UNC Internal Medicine
          AM Report
       August 4, 2009
                       Overview

► Epidemiology
► Pathophysiology
         Presentation
► Clinical
► Diagnosis/Work Up
► Prognosis           Oval fat body under polarized light showing
                      maltese cross.
► Treatment
► Our patient…6 months later
            Epidemiology
► 13.4  cases per million in adults
► onset most commonly 4th to 5th decade
  (idiopathic)
► 75% idiopathic
► FSGS has overtaken MN as most common
  cause of nephrotic syndrome in adults
► 2:1 males : females
   Secondary Membranous Nephropathy




Ponticelli C. Membranous nephropathy J Nephrol 2007;20:268-287.
                Pathophysiology
► circulatingIgG antibodies directed against
  endogenous antigens on or near podocyte foot
  processes form immune complexes
► C5b-9 (MAC) causes cell signaling ->
    silt diaphragm protein disruption
    redistribution of actin
    GBM expansion by injured podocytes
► antigens?: dsDNA, thyroglobulin, hepatitis B
  surface antigen, treponemal antigen, and not yet
  discovered….
                             Pathophysiology




►Glassock   RJ. N Engl J Med 2009;361:81-83.
                               ► Normal   Glomerulus
                                   thin GBM (equivalent to
                                    tubular basement
                                    membrane)
                                   mesangium limited to
                                    stalk of capillary tuft
                                    (double arrows)

                               ► Membranous
                                Nephropathy
                                  thick GBM (in relation to
                                   tubular basement
                                   membrane)
                                  mesangial expansion
                                   (asterisks)
images from www.uptodate.com
                               ► Immunofluorescence
                                   diffuse granular IgG
                                    deposits along GBM

                               ► Silver   Stain
                                   spike pattern in GBM
                                    highlights deposits
                                    between new GBM




images from www.uptodate.com
► Normal   EM
   thin, homogenous GBM
   epithelial cell with foot
    processes
   fenestrated endothelial
    cell (arrow)



► Membranous     EM
   thick GMB, with
    deposits (D)
   effacement of foot
    processes
        Clinical Presentation
► 80%   present with nephrotic syndrome
► hypoalbuninemia and hyperlipidemia most
  often present
► sublinical to more than 20 g/day of
  proteinuria
► 70% have normal BP and normal GFR
           Diagnosis/Work Up
► U/A,   microscopy, UP/C
   > 3.5 g/day
   oval fat bodies, lipid droplets, fatty casts
► Rule   Out Secondary Causes
   ANA/Complement
   SPEP/UPEP
   Hepatitis Serologies, RPR, HIV
     ►cyroglobulins
           Diagnosis/Work Up
► Kidney biopsy is needed for diagnosis, and
  should be done in all patients with
  unexplained nephrotic syndrome
► Lipids
► 5-20% over 65 have malignancy
   age appropriate screening
                 Prognosis
► “rule of thirds”
► complete: 5-30% at 5 y
► partial: (<2 g) 25-40%
  at 5 y
► ESRD: 14% at 5 y, 35%
  10 y, 41 % 15 y
► Toronto
  Glomerulonephritis       Schieppati, A, et al, N Engl J Med 1993; 329:85. Figure www.uptodate.com


  Registry
                     Prognosis
► Good   Prognosis
                            Creatinine levels in patient with complete
   female
                            remission of idiopathic membranous nephropathy
   young age
   normal creatinine
   <4 g proteinuria /day
    for 6 mos
   no tubulointerstitial
    disease
► Poor   Prognosis
   > 8 g proteinuria/day
    for 6 months

                             Ponticelli C. J Nephrol 2007;20:268-287.
         Treatment: Low Risk
► ACE  I or ARB: act, at least in part, to lower
  intraglomerular pressure
► Goal BP <130/80
   may require diuretics
► Lipid-lowering:   statins most often needed
► low salt diet
► anticoagulation: controversial
   highest risk: >12 g/day, albumin <2
 Treatment: Moderate and High Risk
► Moderate:   4-8 g/day x 6 months
   (45% will have spontaneous remission)
   if no better in 6 mos: immunosuppression
► High: > 8 g/day x 6 months or worsening renal
  function
   (75% progress to ESRD)
   cyclophosphamide OR cyclosporine/tacrolimus PLUS
    glucocorticoids
   trial of rituximab
► Transplant:   if ESRD – 10-30% recurrence
               Our Patient…..
► UP/C   is 5.12 (almost
  50% reduction)
► Creatinine stable
► CH 238, HLD 95, LDL
  125
► Taking enalapril 10,
  lipitor 40
► Continues to ride long
  distances on bike
               Key Points
► Membranous    nephropathy only about ¼ of
  all causes of nephrotic syndrome
► 75% idiopathic, but must rule out secondary
  causes
► Rule of Thirds
► Treat symptoms of low risk patients
► Immunosuppression in high risk patieints
                  References
► www.uptodate.com
► Schieppati,  A, Mosconi, L, Perna, A, et al, N Engl J
  Med 1993; 329:85.
► Ponticelli C. Membranous nephropathy J Nephrol
  2007;20:268-287.
► Wasserstein AG. Membranous glomerulonephritis J
  Am Soc Nephrol 1997;8:664-674.
► Glassock RJ. Human idiopathic membranous
  nephropathy--a mystery solved? N Engl J Med
  2009;361:81-83.