Thin Glomerular Basement Membrane: Histopathologic, Ultrastructural, and Molecular Variability
TC Liu, H Liapis. Washington University in St. Louis, St. Louis, MO
Background: Thinning of glomerular basement membrane (GBM) is encountered in about 1% of medical renal biopsies. The most frequent and important question is whether the findings represent Alport. Collagen IVα3 and α5 immunofluorescence (IF) and electron microscopy (EM) can be very helpful in many cases. Alport variants not infrequently are a diagnostic challenge because of variable IF and EM findings. We present the collagen IVα3,5 and EM results of thirty renal biopsies with segmental or diffuse GBM thinning.
Design: Light microscopy, routine and specific IF for Collagen IVα3, α5 minor chains, and EM of 30 renal biopsies from our consult files were reviewed. Demographic data (age, sex, family history and presenting symptoms) were tabulated along with detailed histopathologic findings. GBM thinning was determined based on age and previously determined threshold of ≤ 200 nm.
Results: All patients presented with gross hematuria. Twenty patients (66%) also had varying degrees of proteinuria; three of nephrotic range. Fourteen patients were male and 16 female. The age ranged from 4 to 51 years old (mean = 19.7). Only 5 patients had definitive family history of renal disease (16.4%). Under light microscopy examination, 14 patients showed unremarkable glomeruli (47%), 8 patients showed only mesangial hypercellularity (27%), 5 showed increased global glomerulosclerosis (17%), and 3 had FSGS (10%). IF for α3, α5 (IV) results were as follows: +/+ in 15 biopsies (50%), -/- in 3 (10%), -/+ in 2 (6%), +/- in 1(3%), both chains mosaic in 4 (13%), both decreased in 1. The remaining 4 biopsies had other staining combinations. EM showed thin GBM in all cases; 16 patients showed lamellation within thin segments, 12 of these also had bread crumbs; 14 had diffuse thinning with no lamellation;18 biopsies showed varying degrees of foot process effacement. The diagnosis of X-linked Alport was made in 6, Autosomal-recessive Alport was suggested in 13 (total Alport 19/30=63.5%), TMD in 11/30 (36.6%), of which superimposed glomerular disease was present in 6 (45%): minimal change disease in 3, FSGS in 2, and post-infectious in 1.
Conclusions: In this cohort the majority of thin GBM are either X-L Alport or Alport variant. A significant 45% of TMD was concurrent with another primary glomerular disease which appears to be the likely cause of presenting symptoms. Therefore, TMD in this population was a diagnosis of exclusion. Alternatively, GBM thinning may underline the pathogenesis of glomerular diseases such as FSGS and minimal change disease.
Category: Kidney (does not include tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 248, Wednesday Afternoon