OBJECTIVE-Reduced nephron number is hypothesized to be a risk factor for chronic kidney disease and hypertension. Whether reduced nephron number accelerates the early stages of diabetic nephropathy is unknown. This study investigated whether the rate of development of diabetic nephropathy lesions was different in type 1 diabetic patients with a single (transplanted) kidney compared with patients with two (native) kidneys. RESEARCH DESIGN AND METHODS-Three groups of volunteers were studied: 28 type 1 diabetic kidney transplant recipients with 8-20 years of good graft function, 39 two-kidney patients with duration of type 1 diabetes matched to the time since transplant in the one-kidney group, and 30 age-matched normal control subjects. Electron microscopic morphometry was used to estimate glomerular structural parameters on 3.0 ± 1.4 glomeruli per biopsy. RESULTS-In the one- versus two-kidney diabetic subject groups, respectively, serum creatinine (means ± SD 1.3 ± 0.4 vs. 0.9 ± 0.2 mg/dl; P < 0.001), systolic blood pressure (133 ± 13 vs. 122 ± 11 mmHg; P < 0.001), and albumin excretion rate (median [range] 32.1 (μg/min [2-622] vs. 6.8 (μg/min [2-1,495] ; P = 0.006) were higher. There were no differences in the one- versus two-kidney diabetic subject groups, respectively, in glomerular basement membrane width (median [range] 511 nm [308-745] vs. 473 nm [331-814]), mesangial fractional volume (mean ± SD 0.30 ± 0.06 vs. 0.27 ± 0.07), mesangial matrix fractional volume (0.16 ± 0.05 vs. 0.16 ± 0.06), and mesangial matrix fractional volume per total mesangium (0.61 ± 0.07 vs. 0.64 ± 0.09). However, these glomerular structural parameters were statistically significantly higher in both diabetic subject groups compared with normal control subjects. Results were similar when patients receiving ACE inhibitors were excluded from the analyses. CONCLUSIONS-Reduced nephron number is not associated with accelerated development of diabetic glomerulopathy lesions in type 1 diabetic patients.