1. The efficacy and mode of action of frusemide (100–750 mg) have been studied acutely in thirty-four investigations on twenty-four water-loaded subjects with stable, non-oedematous chronic renal disease (GFR 2.3–26.0 ml/min) of varying aetiology (fourteen ‘tubular’, ten ‘glomerular’).

2. Water loading alone resulted in a slight increase in urine flow rate, a flow-dependent rise in electrolyte excretion and a small fall in urine osmolality.

3. Basal fractional excretion of fluid and electrolytes was closely related to GFR, increasing as this fell, so that at a GFR of 3.0 ml/min 80% of the fluid filtered, 50–60% of the filtered load of sodium and chloride and 400% of potassium was excreted.

4. After oral or intravenous frusemide, up to 93% of the filtered load of chloride, 87% of sodium and apparently all of the glomerular filtrate could be excreted; the magnitude of the response depended on dose, GFR and basal fractional sodium excretion, being greatest at higher GFR and lowest fractional excretion. Free water clearance increased.

5. No significant change in inulin clearance was found after frusemide and no difference in the response of ‘tubular’ as opposed to ‘glomerular’ subjects.

6. Long-term treatment of nineteen patients with ‘resistant’ oedema and chronic renal disease has shown high dosage frusemide (0.12–2.0 g/day) to be an effective diuretic, although significant side effects were found in five patients.

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