Little is known about the role of proteinuria in the progression of childhood renal diseases. We analyzed the decline in creatinine clearance (C Cr) and kidney survival in 225 children (185 males) with chronic renal failure (CRF) due to isolated hypodysplasia or hypodysplasia associated with urological abnormalities. The data were based on the information available in the Italian Pediatric Registry of CRF (ItalKid Project), which includes patients from all of Italy aged <20 years with C Cr levels of <75 ml/min per 1.73 m2. Patients aged <2 years and those with C Cr levels of <20 ml/min per 1.73 m2 or a follow-up of <1 year were excluded from the analysis, as were those receiving angiotensin-converting enzyme inhibitors. At baseline, the patients had a mean age of 7.8±4.2 years, a mean C Cr of 50±16.3 ml/min per 1.73 m2, a median urinary protein/urinary creatinine (uPr/uCr) ratio of 0.38 (range 0.02–7.21), and a mean duration of follow-up of 3.5±1.1 years. The patients were divided into three groups on the basis of their baseline proteinuria levels: group A normal (uPr/uCr <0.2) n=83; group B low (uPr/uCr 0.2–0.9) n=71; and group C mild (uPr/uCr >0.9) n=71. Patients in groups A and B showed a significantly slower decline in C Cr than those in group C (slope +0.16±3.64 and −0.54±3.67 vs. −3.61±5.47, P<0.0001) and a higher rate of kidney survival after 5 years (96.7% and 94.1% vs. 44.9%, P<0.01). By multivariate analysis, the baseline uPr/uCr ratio (P<0.01) and age (P<0.0001) correlated with a faster decline in C Cr irrespective of baseline C Cr. There was no correlation with mean arterial blood pressure. We conclude that proteinuria is an independent predictor of progression to end-stage renal failure also in children whose renal impairment is due to congenital hypodysplasia.