The aim of the present study was to analyze the progression of chronic renal failure (CRF), the effects of modification of risk factors for disease progression, and to formulate a theoretical model of CRF progression in an unselected group of children with CRF. The study was a cross-sectional, retrospective analysis of 92 patients aged 9.2+/-5.8 years with CRF and low-level proteinuria [glomerular filtration rate (GFR) 43+/-18 ml/min per 1.73 m(2), proteinuria 0.57 g/day, range 0-3.9 g/day]. Inclusion criteria were an established diagnosis of CRF and completion of any surgical treatment. The etiology of CRF in the majority of patients was congenital uropathy. Sixty-nine patients observed for longer than 3 years were divided into two groups according to progression of CRF or improvement of GFR. Forty-three patients were on renoprotective therapy. Over a 3-year period GFR decreased in 39 children and improved in 30 children. There were no differences between the groups in the etiology of CRF. Patients with progression of CRF were older ( P<0.08), grew faster ( P<0.004), had higher blood pressure ( P<0.01), and were more often proteinuric ( P<0.03). Arterial hypertension in patients with progression of CRF was resistant to therapy and these patients needed more intensive treatment. Renoprotective therapy led to improvement of kidney function in 50% of patients, and resistance to renoprotective therapy was correlated with increased body mass and height. Patients who received renoprotective drugs showed stabilized kidney function ( P<0.007) and decreased proteinuria ( P<0.05) and blood pressure ( P<0.02), despite higher basal values. In patients on renoprotective therapy in whom CRF progressed despite treatment, proteinuria was persistent in contrast to patients with improvement ( P<0.02). The best model of CRF progression in the path diagram included systolic blood pressure and anthropometric parameters. In conclusion, in unselected patients with CRF of non-glomerular origin and nil-to-moderate proteinuria the main risk factors for CRF progression are rapid somatic growth, age, and blood pressure. Arterial hypertension and proteinuria, even of mild intensity, differ significantly between patients with progression of CRF and those with stable or improved renal function. Renoprotective therapy is related to significant slowing of CRF progression, but the risk factors for resistance to therapy include persistent proteinuria and somatic growth.