High-dose torasemide, given once daily intravenously for one week, in patients with advanced chronic renal failure

Effects, both acute and after repeated dosing of 200 mg of intravenous torasemide in comparison to baseline values on placebo, were investigated with respect to 24 h fractional volume excretion and electrolyte excretion, signs of peripheral edema and changes in body weight in the present open uncontrolled multicenter study. Fourty-four patients with advanced chronic renal failure (mean creatinine clearance 8.9 +/- 9.6 ml/min, range 1.1-63.7 ml/min) were enrolled after they had given their informed consent. The increase vs placebo in the primary efficacy variable 24 h fractional volume excretion was statistically significant both acutely (p = 0.0001) and after repeated daily injections (p = 0.0012). The acute changes of the means of fractional volume excretion (from 14.32% to 21.07%) and of absolute 24 h urinary volume (from 1303 ml to 2124 ml) were as expected from earlier data. In addition to the acute results our study showed that after seven days of daily injections there was still a considerable diuretic effect (mean fractional volume excretion: 18.10%, absolute 24 h urinary volume: 1664 ml). Our data support earlier results in that the change in fractional potassium excretion was considerably smaller than that of sodium of chloride excretion. However, this effect which was more pronounced after acute administration of torasemide seems to vanish after repeated dosing. After repeated dosing there was only a minor change in calcium excretion and there was no alteration in phosphate excretion, neither acutely nor with repeated dosing. Along with the enhanced diuresis there was a relevant reduction in body weight and a clinical significant improvement preexisting signs of peripheral edema. Torasemide was found to be also efficacious in patients on hemodialysis (with residual diuresis of > or = 300 ml): after the first i.v. dose of 200 mg torasemide the mean fractional volume excretion was increased from 16.22% at baseline by 3.42% to 18.99% (in absolute 24 h urinary volume from 1044 ml at baseline by 563 ml to 1607 ml). In parallel, the mean fractional sodium excretion was increased from 8.67% at baseline by 2.99% to 11.14% (in absolute 24 h urinary sodium excretion from 83.3 mmol at baseline by 51.2 mmol to 128.0 mmol). There was no serious adverse events related to the administration of torasemide. Torasemide appears to be a good choice for the treatment of patients with renal failure.