[1542] Pathogenesis of Minimal to Mild Diabetic Glomerulopathy

LC Stout. University of Texas Medical Branch, Galveston, TX

Background: Textbooks say that (1) the main mesangial destructive lesions in diabetic glomerulopathy are the diffuse lesion (DL) and the nodular lesion (NL), (2) the DL is far more common and more highly associated with renal insufficiency than the NL, and (3) the NL never develops in the absence of significant DL. These conclusions were based mostly on the study of advanced lesions. As far as I know, the pathogenesis of minimal to mild diabetic glomerulopathy has not been determined.
Design: Seventy four diabetic (end stage cases were excluded) and 59 matched control cases were retrieved from consecutive UTMB autopsies. Twenty five cases had minimal to marked mesangial lesions. About 100 glomeruli from each of these 25 cases were studied using 18 4 micron paraffin embedded serial sections stained as follows: PAS, IgG, IgM, PAM, Trichrome, IgA, Albumin, Lysozyme, PAS, Fibrinogen, Fibronectin, PAM, Trichrome, Kappa and Lambda light chains, LCA, PAS and Actin. Starting at PAS-9, NLs, focal mesangiolyses (FMs) and non NL peripheral mesangial expansions (PMEs) > 40 microns were traced through the serial sections, noting their dimensions and other characteristics. PMEs between 15 and 40 microns were counted, and the DL graded on a scale of 0-5+ (0 is normal, 5+ is 5 times normal) in the same glomeruli in PAS-9 only.
Results: NLs, FMs and FMEs always occurred at the periphery of lobules. Ten cases with the least number of these lesions are presented here (7 males and 3 females, mean ages 58 and 69, respectively, mean duration of diabetes 18 yrs, 9 type II and 1 type I diabetes). Mean number of traced glomeruli with lesions was 9.2 (4-15) in PAS-9. Mean number of total lesions (NLs, FMs and PMEs >40 microns) in traced glomeruli in all sections was 15.9 (0-38), 4.3 (0-11) and 5.4 (0-15), respectively. Mean number of PAS-9 glomeruli with PMEs 15-40 microns was 14 (5-31), and mean number of these smaller PMEs was 18.2 (5-35). Two cases had + DL, 4 had ++ DL and 4 had ++variable DL (>++ in afferent primary branches, but <++ in predominantly efferent areas. DL grade ++ would be considered mild by most renal pathologists, but sufficient to suggest diabetes if at least 20 glomeruli were available. Most lesions were modest in size, but 4 cases had a total of 3 laminated NLs up to 80x80 microns and 3 FMs up to 80x100 microns. Another case with + DL had 2 large laminated NLs, 1 with an FM and 1 with a microaneurysm 70x80 microns.
Conclusions: The findings in these 10 cases indicate that destructive mesangial lesions all occurred at the periphery of lobules, and developed in the presence of minimal to mild DL.
Category: Kidney (does not include tumors)

Wednesday, March 24, 2010 1:00 PM

Poster Session VI # 247, Wednesday Afternoon

 

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