The acute effect of acetazolamide on glomerular filtration rate and proximal tubular reabsorption of sodium and water in normal man

The acute effects on kidney function of acetazolamide (250 mg) given intravenously were evaluated in seven healthy subjects. Glomerular filtration rate was measured as the renal clearance of ^5lCr-EDTA, and fluid flow rate out of the proximal tubules was assessed by measurement of the renal lithium clearance. An 18% decline in glomerular filtration rate (ml/min) was observed after acetazolamide administration (109±16 vs 89±14, p<0.02), while lithium clearance (ml/min) increased by 35% (30±5 vs 38±8, p<0.02). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one third (79±12 vs 51±9, p<0.02), and fractional proximal reabsorption of water and sodium (% declined (73±2 vs 58±6, p<0.02). Renal sodium clearance and absolute distal reabsorption of sodium increased, while fractional distal reabsorption of sodium declined. Acetazolamide reduces absolute and fractional proximal tubular reabsorption of sodium and water, and glomerular filtration rate. Primarily, this induces an increase in the output of fluid from the proximal tubules accounting for the diuretic effect of the drug. The acute fall in glomerular filtration rate is probably mediated by a temporary increase in proximal intratubular pressure and activation of the tubuloglomerular feedback mechanism.