Abstract
Nodular glomerulosclerosis is a distinct entity that is highly specific for diabetic glomerulopathy. However, clinicopathologic characteristics of this nodular lesion are largely undefined in patients with type 2 diabetes. An autopsy study was conducted to investigate the clinical, histopathologic, and histochemical characteristics of 351 consecutive cases with type 2 diabetes. In addition, immunohistochemical staining was performed in a representative subset of 50 cases. Nodular glomerulosclerosis was found in 37.6%. Hypertension, elevated serum creatinine and urea levels, renal failure, myocardial infarction, low body mass index, and large glomerular matrix area were the significant risk factors for nodular glomerulosclerosis. Proteinuria (protein > 0.5 g/24 h), renal insufficiency (serum creatinine > or = 2.0 mg/dL [> or =178 micromol/L]), and renal failure were found in 28.1%, 33.6%, and 7.6% of patients with type 2 diabetes with nodular glomerulosclerosis, respectively. Glomerular matrix fractions were 42.1% +/- 13.3%, 32.3% +/- 15.3%, and 22.7% +/- 8.0% in patients with nodular glomerulosclerosis, non-nodular glomerulopathy (glomerulopathy in the absence of Kimmelstiel-Wilson nodule), and near-normal glomeruli with age-related minimal changes, respectively (analysis of variance, P < 0.001). Immunoreactivity for collagen type IV, fibronectin, and laminin was localized at the periphery of mesangial nodules. Mesangial cells at the periphery of mesangial nodules showed increased staining intensity for alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta1 (TGF-beta1). Nodular lesions also showed a marked increase in number of glomerular CD68-positive macrophages. In patients with type 2 diabetes, nodular glomerulosclerosis is related to hypertension, advanced renal disease, and prevalent myocardial infarction. Glomerular macrophage infiltration, expression of alpha-SMA by mesangial cells, and overexpression of TGF-beta1 are the cellular changes associated with abnormal extracellular matrix deposition in nodular glomerulosclerosis.
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