NDT Advance Access originally published online on August 22, 2005
Nephrology Dialysis Transplantation 2005 20(11):2582-2583; doi:10.1093/ndt/gfi085
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Comparison of the urine acidification tests of torsemide vs furosemide in healthy volunteers
Sir,The gold standard test to assess the ability to lower urine pH has traditionally been based on orally administered ammonium chloride (NH4Cl) [1]. The use of ammonium chloride for this purpose is not well accepted because the drug has unpredictable GI absorption when given in tablet form and has an unpleasant taste when administered in a powder form. Furthermore, ammonium chloride causes many unpleasant side effects such as abdominal discomfort, nausea and vomiting. An alternative drug used to assess the ability to lower the urine pH with increasing popularity is a loop diuretic, furosemide, which blocks the sodium–potassium–chloride co-transporter (NKCC) in the thick ascending limb of Henlé. One drawback of the furosemide acidification test is a low specificity (82–89%) [2,3]. The likely reason for the low specificity is the carbonic anhydrase inhibitory effect, which is attributed to the presence within the molecule of a sulfonamide moiety [4,5]; this latter effect would partially negate the stimulatory effect on acid secretion by furosemide. In contrast, another loop diuretic, torsemide, contains a sulfonylurea moiety, instead of a sulfonamide moiety, and therefore is devoid of the carbonic anhydrase inhibitory effect. For these reasons, it is hypothesized that torsemide would be more specific in detecting acidification defects than furosemide, and the following studies were carried out to test this hypothesis.
Studies were carried out in eight healthy male volunteers (aged 23–33 years) utilizing a single-blind randomized crossover format. Urine samples were collected immediately before oral administration of 40 mg furosemide or 20 mg torsemide, and then hourly for 4 h after oral administration of the diuretic. Studies were repeated in the same subjects with the intravenous administration of the same medications in the same doses. pH measurements were made in all the urine samples, but only the baseline urine pH and the lowest urine pH following a loop diuretic were used for data analysis.
The baseline urine pH values were similar in all groups. The values with torsemide were 6.2±0.2 (mean±SE) with a range of 5.7–7.1 after oral administration and 6.2±0.2 with a range of 5.6–7.2 after intravenous administration. The values after furosemide were 6.3±0.3 with a range of 5.5–7.3 after oral administration, and 6.3±0.2 with a range of 5.6–7.4 following intravenous administration. However, urine pH after the administration of torsemide was significantly lower than after that of furosemide (P<0.05), regardless of the routes of administration. The values for torsemide were 4.9±0.1 with a range of 4.5–5.2 after oral administration, and 4.9±0.1, with a range of 4.5–5.6 after intravenous administration. The values for furosemide were 5.6±0.2 with a range of 4.9–7.0 after oral administration, and 5.5±0.2 with a range of 5.0–6.5 after intravenous administration. For furosemide, urine pH remained >5.5 in four of eight subjects after oral administration, and two of eight after intravenous administration. For torsemide none had urine pH >5.5 after oral administration, and only one of eight subjects after intravenous administration. If we define urine pH <5.5 following a loop diuretic in normal subjects as a true normal result [6], the specificity of furosemide test was 50% with oral administration and 75% after intravenous administration, whereas for torsemide they were 100% after oral administration and 88% after intravenous administration, respectively. No subjects developed any significant adverse effects with either loop diuretic regardless of the routes of administration.
In conclusion, torsemide appears to be as safe and simple as furosemide in testing the maximum ability to lower the urine pH, with greater specificity than the latter. However, the sensitivity of this test needs to be determined in subjects with impaired urine acidification.
Conflict of interest statement. None declared.
1 Department of Internal Medicine Hanyang University Guri Hospital Guri Korea2 Department of Medicine State University of New York Health Science Center at Brooklyn Brooklyn NY, USA Email: kimhj{at}hanyang.ac.kr
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