Diabetic Nephropathy and Fibrillary Glomerulopathy: An Unusual and Problematic Double Glomerulopathy
Josephine M Ambruzs, Christopher P Larsen, Fred G Silva, Patrick D Walker. Nephropath, Little Rock, AR; University of Arkansas for Medical Sciences, Little Rock, AR
Background: The clinical diagnosis of diabetic nephropathy (DN) may be incorrect in as many as 45% of cases often leading to renal biopsy for definitive diagnosis and exclusion of non-diabetes related renal disease. A significant challenge in the interpretation of these biopsies is the recognition of an underlying or coexisting primary glomerular disease with morphologic features that overlap with those of DN. We report the first clinicopathologic series to date of renal biopsies in patients with coexisting DN and fibrillary glomerulopathy (FG), a rare entity that shares similar clinical demographics and morphologic features.
Design: A search of our database of native renal biopsies from the last 11 years identified 301 cases of FGN (0.89%) and 5289 cases of DN (15.7%). 11 patients with DN had a concomitant diagnosis of FG (0.2%). Standard processing of biopsies included light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM).
Results: Mean age was 60 years (range 41-74) and the female to male ratio was 1.2:1. 8 patients (73%) were Caucasian, 2 were African American and 1 was Native American. Duration of diabetes was 5 to 30 years and 27% had documented retinopathy and/or neuropathy. The most common indication for biopsy was chronic progressive renal failure (45%), nephrotic syndrome (27%), acute on chronic progressive renal failure (19%) and sub-nephrotic proteinuria (9%). The mean creatinine was 2.2 mg/dL (range 1.0-3.5). 4 patients had hepatitis C virus (36%), 1 had prostate carcinoma and 1 had an IgA kappa monoclonal gammopathy of unknown significance. By LM, 10 had diffuse and nodular glomerulosclerosis while 1 showed diffuse mesangial matrix expansion and thickened glomerular basement membranes (GBM). All showed ≥2+ “smudgy” glomerular staining for IgG with no evidence of light chain restriction. Linear, non-branching fibrils were present within the mesangium and, importantly, in the GBM in all cases. Compared to the fibrils normally seen in DN, the fibrils of FG were much larger and easily visualized at 12000X.
Conclusions: Recognition of FG in patients with DN can be problematic given their clinical and morphologic overlap. However it is critical to recognize this co-occurrence given the difference in therapeutic regimen and outcome versus DN alone. This series demonstrates that a glomerular IF pattern of smudgy rather than linear IgG as well as the presence of typical large FG fibrils in both the mesangium and the GBM are the most useful diagnostic criteria leading to a correct diagnosis in these patients.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 240, Monday Afternoon