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Friday, June 27, 2014

Topic Discussion: Diabetic Nephropathy Pathology Classification


As we all know that if there is a clinical history of DMII in someone with proteinuria or renal disease,   DM nephropathy is always on the differential on what one might find on the kidney biopsy.
Take a look at this recentpathology classification of DMII nephropathy. It starts off at classifying it in terms of mesangial expansion and leading to the classic KW lesions. It reminds you of a lupus classification but in this case, its more progressive. This article in JASN published many years ago has been the proposal paper. I am hoping validation studies are underway to confirm this. Does this help us as clinicians? Or is it more for pathologists to have a better handle on how to diagnose DM on kidney biopsy as presentations can be so variable.  Looking at the classification, I think the diagnosis of DM nephropathy will increase. Class I is more of just EM changes of GBM thickening. IIa and IIb are the classic mesangial expansion.  The KW lesion is the cornerstone of Class III and IV is bad advanced diabetic glomerulosclerosis.

Class
Description
Inclusion Criteria
I
Mild or nonspecific LM changes and EM-proven GBM thickening
Biopsy does not meet any of the criteria mentioned below for class II, III, or IV
GBM > 395 nm in female and >430 nm in male individuals 9 years of age and oldera
IIa
Mild mesangial expansion
Biopsy does not meet criteria for class III or IV
Mild mesangial expansion in >25% of the observed mesangium
IIb
Severe mesangial expansion
Biopsy does not meet criteria for class III or IV
Severe mesangial expansion in >25% of the observed mesangium
III
Nodular sclerosis (Kimmelstiel–Wilson lesion)
Biopsy does not meet criteria for class IV
At least one convincing Kimmelstiel–Wilson lesion
IV
Advanced diabetic glomerulosclerosis
Global glomerular sclerosis in >50% of glomeruli
Lesions from classes I through III
 Table from JASN paper from above.
What we learned in medical school was one of the secondary causes of membranous GN pattern on injury was diabetes.  Classically, in practice I have rarely seen that. We classically see the mesangial changes and KW lesions. The thickening and EBM changes can appear like Membranous GN on biopsy but there are no classic deposits and there is no mention of those changes on the above classification scheme.  Membranous GN that is primary in nature can likely to co-exist with DM nephropathy. Others have mentioned this as well on websites. There is only one association I found of this in the literature and that was related to potential insulin deposits that were seen in some patients with DM that developed membranous GN and that suggestive of the pathogenetic role in the presentation. 
Diabetes rarely presents as a membranous pattern. The above mentioned patterns are the most common presentations of DMII.



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