Chronic renal disease with elevated level of serum creatinine (Cr) often progresses to end-stage renal disease. Although blockade of the renin-angiotensin system has been shown to slow the progression of chronic renal disease, it remains uncertain whether one could expect such a renoprotective effect even when the treatment is initiated late in the course of renal disease. The purpose of the present study was to examine the effect of losartan, an angiotensin-II receptor antagonist, on the progression of advanced renal insufficiency. We retrospectively analyzed eight hypertensive patients, whose baseline Cr levels exceeded 2.0 mg/dl (2.2-5.5); the subjects included 6 non-diabetic glomerular diseases, 1 diabetic nephropathy and 1 polycystic kidney disease. Losartan was given at the dosage of 25-50 mg/day. Changes in mean blood pressure (MBP) and serum levels of Cr, potassium (K) and uric acid were evaluated after treatment for 24 weeks. Slopes of reciprocal of serum Cr plotted against time (1/sCr slope), which indicate the rate of renal function loss before and after the treatment period, were compared. There was a significant reduction of 1/sCr slope after losartan (-0.004 +/- 0.002 dl/mg/week before and -0.001 +/- 0.002 dl/mg/week after the treatment, p < 0.05). MBP and serum levels of Cr, K and uric acid were not changed significantly by losartan treatment. However, improvement of 1/sCr slope was correlated to the degree of MBP changes. Based on the available data from 4 patients, proteinuria was decreased in 3 patients. These results suggest that losartan may retard the progression of advanced renal insufficiency.