Preterm birth is associated with decreased nephron mass and obesity that may impact on kidney disease progression in later life. Our objectives were to examine the relative risks of obesity and preterm birth on the progression of kidney disease in children. In a retrospective cohort study, 80 (44 obese and 36 non-obese) patients with proteinuric kidney disease were studied for disease progression and glomerular histomorphometry. Of the obese, 22 had been born at term (Obese-T) and 22 had been preterm (Obese-PT). Seventeen non-obese children with focal glomerular sclerosis, born at term (NO-FSGS), and 19 non-obese preterm (NO-PT) children, served as controls. Insulin resistance as measured by the homeostatic model assessment (HOMA-IR) was elevated in all obese children. Obese-PT patients had increased risk of renal demise during childhood when compared with Obese-T children [hazard ratio 2.4; 95% Confidence interval (95% CI) 1.1 to 7.1; P = 0.04]. In obese children, although proteinuria often exceeded nephrotic range, average levels of serum albumin remained normal. Preterm patients were more likely to have reduced renal mass (odds ratio 4.7; P = 0.006), but obesity was not a factor. Renal histomorphometry showed glomerulomegaly in obese patients, regardless of birth weight. Obesity and preterm birth appear to impose additive risks for progression of kidney disease in childhood.