Malnutrition at the initiation of dialysis is a strong predictor of subsequent increased mortality on dialysis. Few studies have documented the relationship between the progression of renal failure and spontaneous dietary protein intake (DPI) and other indices of malnutrition. In this prospective study, renal function was sequentially measured by creatinine clearance (CrCl) and DPI by 24-h urine collection; simultaneously, multiple sequential biochemical nutritional indices, including serum albumin, transferrin, prealbumin, and insulin-like growth factor-I (IGF-I) concentrations, were measured. The study involved 90 patients (46 men and 44 women) with chronic renal failure (CRF) of various causes monitored in an outpatient clinic. Dietary interventions were minimal. The mean duration of follow-up was 16.5 +/- 11.8 months. The results show that the mean (+/- SD) DPI was 1.01 +/- 0.21 g/kg per day for patients with CrCl over 50 mL/min and decreased to 0.85 +/- 0.23 g/kg per day for patients with CrCl between 25 and 50 mL/min. The DPI further decreased to a level of 0.70 +/- 0.17 g/kg per day for patients with CrCl between 10 and 25 mL/min and was 0.54 +/- 0.16 g/kg per day for patients with CrCl below 10 mL/min. This trend was statistically significant (P < 0.001). A similar statistically significant trend was observed for serum cholesterol, transferrin, and total creatinine excretion (all P < 0.01). A mixed model analysis indicated that for each 10 mL/min decrease in CrCl, DPI decreased by 0.064 +/- 0.007 g/kg per day, transferrin decreased by 16.7 +/- 4.1 mg/dL, weight decreased by 0.38 +/- 0.13% of initial weight, and IGF-I decreased by 6.2 +/- 1.9 ng/mL. It was concluded that the progression of renal failure is associated with a spontaneous decrease in DPI, especially below a CrCl of 25 mL/min, and that most nutritional indices in CRF patients worsen as CrCl and DPI decrease. Dietary protein restriction should be used cautiously in CRF patients when CrCl falls below 25 mL/min.