From the results of the Modification of Diet in Renal Disease (MDRD) study, a prediction equation for a more accurate estimate of glomerular filtration rate (GFR), was developed. The present study ais to compare the GFR estimated by MDRD formula and that calculated by the average of creatinine and urea clearances in unselected patients with advanced renal failure. The study group consisted of 320 (163 males) with advanced renal failure not yet on dialysis. Their mean age was 63 +/- 14 years. Diabetic nephropathy was the most common etiology of renal failure (25%). Significant comorbidity was observed in 115 patients. Serum creatinine (Cr), urea and albumin were determined in all patients. Creatinine (Ccr) and urea clearance (Cu) were calculated on a 24-hour urine collection. The GFR was estimated by summing Ccr and Cu, and dividing by two (Ccr-Cu). THe clearances were corrected for a body surface area of 1.73 m2. The MDRD formula for the estimation of GFR included the following parameters: serum Cr, BUN, age, gender and serum albumin. Linear regression analysis and Bland-Altmann plot were utilized to establish the degree of correlation and agreement between both estimations of GFR. The percent differences between the two estimations of GFR was especially analyzed in those subgroups of patients which were not included in the MDRD study (patients older than 70 years, diabetics and those with comorbid conditions). The mean GFR estimated by Ccr-Cu and by MDRD formula were 10.04 +/- 3.10 ml/min and 10.55 +/- 3.60 ml/min, respectively (p < 0.0001). The two parameters correlated significantly (R = 0.76, p < 0.0001). GFR by the MDRD formula tended to overestimate the highest values of Ccr-Cu. The mean percent difference between both methods was 6.5 +/- 23.6. MDRD predictive equation overestimated significantly Ccr-Cu in patients older than 70 years (mean overestimation of 15%), males (10%), diabetics (10%), and mainly in patients with comorbidity (17%). In conclusion, the GFR estimated by MDRD formula is very similar to Ccr-Cu in young uremic patients without comorbidity. However, major discrepancies between these two methods could be observed in older patients, and mainly in those with comorbidity.