1. http://www. dcss. cs. amedd. army. mil/field/FLIP%20Disk%2041/FLIP

2. http://www. dcss. cs. amedd. army. mil/field/FLIP%20Disk%2041/FLIP

10. Idiopathic Membranous Nephropathy
Paul M. Johnson
UNC Internal Medicine
AM Report
August 4, 2009

11. Overview Epidemiology Pathophysiology Clinical Presentation
Diagnosis/Work Up
Prognosis
Treatment
Our patient…6 months later
Oval fat body under polarized light showing
maltese cross.

12. 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

13. Secondary Membranous Nephropathy
Ponticelli C. Membranous nephropathy J Nephrol 2007;20:

14. Pathophysiology
circulating IgG 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….

15. Pathophysiology
Glassock RJ. N Engl J Med 2009;361:81-83.

16. Membranous Nephropathy
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

17. Immunofluorescence Silver Stain
diffuse granular IgG deposits along GBM
Silver Stain
spike pattern in GBM highlights deposits between new GBM
images from

18. Normal EM Membranous EM thin, homogenous GBM
epithelial cell with foot processes
fenestrated endothelial cell (arrow)
Membranous EM
thick GMB, with deposits (D)
effacement of foot processes

19. 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

20. Diagnosis/Work Up U/A, microscopy, UP/C Rule Out Secondary Causes
> 3.5 g/day
oval fat bodies, lipid droplets, fatty casts
Rule Out Secondary Causes
ANA/Complement
SPEP/UPEP
Hepatitis Serologies, RPR, HIV
cyroglobulins

21. 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

22. 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 Registry
Schieppati, A, et al, N Engl J Med 1993; 329:85. Figure

23. Prognosis Good Prognosis Poor Prognosis female young age
normal creatinine
<4 g proteinuria /day for 6 mos
no tubulointerstitial disease
Poor Prognosis
> 8 g proteinuria/day for 6 months
Creatinine levels in patient with complete remission of idiopathic membranous nephropathy
Ponticelli C. J Nephrol 2007;20:

24. 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

25. 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

26. 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

27. 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

28. 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 ;20:
Wasserstein AG. Membranous glomerulonephritis J Am Soc Nephrol 1997;8:
Glassock RJ. Human idiopathic membranous nephropathy--a mystery solved? N Engl J Med 2009;361:81-83.