Idiopathic nodular glomerulosclerosis is an enigmatic condition closely resembling diabetic nodular glomerulosclerosis without evidence of diabetic mellitus or other specific disease. Idiopathic nodular glomerulosclerosis remains a rare disease entity with an unclear pathogenesis. Clinicopathologic features of 15 patients with idiopathic nodular glomerulosclerosis were evaluated in a retrospective review of renal biopsies between 1998 and 2007. Our study cohort consisted predominantly of older (mean age, 64.2 years) white (73%) women (67%). Fourteen patients (93%) had a history of hypertension, and 10 (67%) were active smokers at the time of biopsy. Nine patients (60%) were obese (body mass index, >30 kg/m(2)) and 4 (27%) were overweight (body mass index, 25-29.9 kg/m(2)). Fourteen patients (93%) presented with renal insufficiency with mean serum creatinine level of 2.8 mg/dL. All 15 patients presented with proteinuria (mean urinary protein excretion, 5.6 g/24 h). Eleven patients (73%) presented with nephrotic-range proteinuria and 8 (53%) with nephrotic syndrome. Histopathologic findings showed nodular glomerulosclerosis (100%), moderate to severe arterio-arteriolosclerosis (100%), and glomerular basement membrane thickening (100%). Immunofluorescence and electron microscopy studies had no other specific findings. Our results confirm previous studies of a close association of hypertension and smoking with idiopathic nodular glomerulosclerosis. A significantly higher incidence of obesity and overweight in patients with idiopathic nodular glomerulosclerosis suggests that increased body mass index may also contribute to the development and progression of idiopathic nodular glomerulosclerosis.