The Renal Clearance of Thiosulfate With Observations on Its Volume Distribution

Gilman, Alfred G.; Philips, Frederick S.; Koelle, Ethol S.

doi:10.1152/ajplegacy.1946.146.3.348

Cited by 101 publications

(43 citation statements)

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“…More than 50 years ago, a good correlation between renal TS and inulin or creatinine clearance was shown (32,33). This was explained by the assumption that TS mainly undergoes glomerular filtration without quantita- tive tubular secretion or reabsorption.…”

Section: Discussionmentioning

confidence: 99%

“…The nonrenal clearance varies even between HV ( Table 2, Table 4). Therefore, the GFR determined by Newman and Gilman (32,33) required the exogenous administration of STS and the simultaneous measurement of TS in serum and urine. The nonrenal elimination of TS accounts for about 50% in HV, an observation consistent with previous investigations in humans and dogs (4,34).…”

Section: Discussionmentioning

confidence: 99%

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Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Farese¹,

Stauffer²,

Kalicki³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet.Design, setting, participants, & measurements STS was given intravenously to 10 hemodialysis patients onand off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method. ResultsIn volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5 Ϯ 1.82 versus 7.1 Ϯ 2.7 mol/L. Renal clearance was high in volunteers (1.86 Ϯ 0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25 Ϯ 0.32 ml/min per kg) than in anuric patients (2.04 Ϯ 0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62 Ϯ 1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%). ConclusionsGiven the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Farese¹,

Stauffer²,

Kalicki³

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…Thiosulfate is known to enter the red blood cells (1) and if it enters these cells it may enter others. Gilman, Philips, and Koelle (9) found that in dogs about one-fourth of the inj ected thiosulfate cannot be recovered and they concluded, on good evidence, that most of the irretrievable fraction disappeared during and j ust after the infusion. The incomplete recovery was confirmed, for man, by Cardozo and Edelman.…”

Section: Discussionmentioning

confidence: 98%

An Evaluation of the Single Injection Thiosulfate Method for the Measurement of Extracellular Water1

Chesley¹,

Lenobel²

1957

J. Clin. Invest.

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The purpose of this paper is to examine the validity of the single injection thiosulfate method, proposed by Cardozo and Edelman (1) for the measurement of the extracellular fluid volume. The conclusion is that the method does not give a valid estimate of the extracellular fluid volume and probably does not even measure the volume of distribution potentially available to thiosulfate.Cardozo and Edelman gave an accurately known amount of sodium thiosulfate (about 10 gm. of Na2S2O3 5 H20 in 10 per cent solution) by intravenous injection over a period that varied from 7 to 16 minutes. They then collected venous blood samples at intervals and plotted the logarithms of the serum thiosulfate concentrations against time. The points usually fell on a straight line; this was extrapolated back to zero time, which arbitrarily was set as the moment the infusion had been started. If the points did not fall on a straight line, the test was discarded because of the variable clearance rate of the thiosulfate. The extrapolated value for serum concentration of thiosulfate (P.) is presumed to be what the concentration would be if the thiosulfate were instantaneously injected and evenly distributed in its final volume of dilution. This extrapolated P0 is then divided into the total amount of thiosulfate injected to calculate the volume of distribution.Aside from the fact that virtually none of the thiosulfate has been injected at this zero time, the method is based upon rather questionable assumptions, which will be discussed later.In some of the evaluations of the single injection method that follow, comparisons were made between the volumes of distribution of thiosulfate and sucrose as calculated by different methods. The other procedures used were the infusion/ slope method devised by Schwartz (2) and the calibrated infusion (IV minus UV) method of Deane, Schreiner, and Robertson (3). MATERIAL AND METHODSAll experiments were done with hospitalized women. While they were not "normal," they were selected.Patients with any discernible cause for disturbance in hydration, such as fever, renal disease or heart disease, were excluded. All In the calibrated infusion method this solution was given intravenously at the rate of 1.05 to 1.10 ml. per minute. Half-hourly collections of venous blood and of urine were begun 2 hours after the start of the infusion. After the collection of 3 or 4 blood and urine samples the thiosulfate was given for the single injection procedure.In measuring the volume of sucrose distribution by the 327

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“…Prior to determination of mannitol, PAH was acetylated as suggested by Barker and Clark (11). Thiosulfate was determined by the method of Gilman, Phillips and Koelle (12), as modified by Elliott and Scott (13). True glucose was determined by the method of Nelson (14).…”

Section: Methodsmentioning

confidence: 99%

The Nature of the Renal Circulatory Changes in Chronic Congestive Failure as Reflected by Renal Tubular Maximal Functions 12

Grossman¹,

Weston²,

Halperin³

et al. 1950

J. Clin. Invest.

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The Renal Clearance of Thiosulfate With Observations on Its Volume Distribution

Cited by 101 publications

References 0 publications

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

An Evaluation of the Single Injection Thiosulfate Method for the Measurement of Extracellular Water1

The Nature of the Renal Circulatory Changes in Chronic Congestive Failure as Reflected by Renal Tubular Maximal Functions 12

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