Angiotensin II receptor antagonists have become clinically available for the treatment of arterial
hypertension. Presently, there is little information about their effects on BP,
proteinuria, and renal function in patients with moderate or advanced
renal failure. This study examines the effects of the
angiotensin II antagonist
Valsartan (80 mg/d) on
proteinuria and glomerular permselectivity in patients with
chronic renal failure during a 6-mo treatment, using a double-blind, randomized, placebo-controlled study (treatment group [V-group]: n = 5, age 57 +/- 7 yr, serum
creatinine 365 +/- 122 micromol/L; placebo group [P-group]: n = 4, age 62 +/- 11 yr, serum
creatinine 346 +/- 61 micromol/L). Study parameters included BP, 24-h
proteinuria, GFR, and effective renal plasma flow (ERPF) as determined by
inulin and para-aminohippurate clearance. Changes in glomerular permselectivity were assessed by measuring the fractional clearances of neutral
dextrans by HPLC gel-permeation chromatography.
Valsartan lowered the mean arterial pressure on average by 13 +/- 7 mmHg during the 6-mo treatment (P < 0.05). GFR and ERPF remained almost unchanged. However, after 6 mo of
Valsartan treatment,
proteinuria was reduced by 396 +/- 323 mg/24 h (26 +/- 18%) and
albuminuria by 531 +/- 499 mg/24 h (41 +/- 21%) with regard to baseline values (P < 0.05). In the P-group, both
proteinuria and
albuminuria increased slightly with time (by 30 +/- 43% and 30 +/- 54%, respectively, NS). The fractional clearances of high molecular weight
dextrans >66 A were significantly reduced after 6 mo of
Valsartan treatment (P < 0.05), indicating a reduction of the glomerular shunt volume by 54 +/- 20% (P < 0.05) according to the model of Deen et al. (Am J Physiol 249: 347-389, 1985). The mean pore size radius of the glomerular membrane remained unchanged. This effect was independent of glomerular hemodynamic changes.
Valsartan persistently lowered
proteinuria in patients with
chronic renal failure. Although GFR and ERPF remained nearly stable, this effect could be attributed to an improvement in glomerular permselectivity.