Clinicopathologic characteristics of nodular glomerulosclerosis in Chinese patients with type 2 diabetes.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Zhao
Hai-Lu
HL
Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, SAR, China. zhaohailu@cuhk.edu.hk
Lai
Fernand M M
FM
Tong
Peter C Y
PC
Tomlinson
Brian
B
Chan
Juliana C N
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001344:Autopsy; D002681:China / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D005260:Female; D005921:Glomerulonephritis / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged