Frusemide test for renal acidification defects
Renal tubular acidosis is characterised by an hyperchloraemic acidosis with a normal anion gap. The diagnosis is already established if there is alkaline urine (pH > 5.5) despite a metabolic acidosis (plasma bicarbonate < 17.5 mmol/L) in the presence of a normal GFR.
The main indication for this pharmacological test for subtle renal tubular acidosis is in the differential diagnosis of the aetiology of renal stones when early morning urine has a pH > 5.5. It is a useful first line screening test for these patients.
Principle of the test
Administration of frusemide results in an increase in the delivery of sodium ions to the distal renal tubules with a normal quantity of bicarbonate ions. A proportion of the extra sodium is reabsorbed in exchange for H+ ions in normal individuals resulting in an acid urine. This test stresses the distal tubules acidification ability.
Patient is fasted overnight.
Spironolactone should be discontinued for 6 weeks prior to this test.
- 9 urine sample containers
- 40 mg frusemide tablet
- baseline urine sample for pH,
- 0900 oral administration of 40 mg frusemide
- 0930-1300 urine samples collected every 30 min (8 samples) and analysed for pH
A normal response is a lowering of urine pH to less than 5.5 by 4 hours. A nadir in urinary pH should be achieved by 3-4 hours. The frequent urine pH measurements are necessary to avoid misclassification of some patients.
The diagnostic performance of this test for the diagnosis of RTA in renal stone formers is: sensitivity 10%, specificity 82%, predictive value of a positive test 40%, predictive value of a negative test 100%. In view of the relatively poor predictive value of a positive test, patients with a positive test should progress to the ammonium chloride acidification test for confirmation.
- Reynolds TM, Burgess N, Matanhelia S, Brain A, Penney MD. The frusemide test: simple screening test for renal acidification defect in urolithiasis. Br J Urol 1993;72:153-156.