Inorganic sulfate and thiosulfate: transport and competition in renal tubules of the dog

Berglund, Fredrik; Helander, C. G.; Howe, Robert B.

doi:10.1152/ajplegacy.1960.198.3.586

Cited by 19 publications

(9 citation statements)

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“…It might be at least partially explained by the STS degradation in the acidic environment of the stomach (Na 2 S 2 O 3 ϩ 2HCl 3 2NaCl ϩ H 2 O ϩ S ϩ SO 2 ). Alternatively, the low and variable bioavailability may be due to STS degradation by intestinal bacteria (26) and/or different expression levels of a putative TS transporter in the gut mucosa, which might exist in analogy to a sulfate-inhibitable TS transporter in the dog renal tubule (27). Interestingly, despite the very low oral bioavailability of STS, the successful prevention of renal stones in humans (28), and rats (29), and of the progression of calciphylaxis (30) and nephrocalcinosis (31) has been reported by comparable oral STS doses as those used in our investigation.…”

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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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%

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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“…Berglund and Lotspeich (12,17) found in dogs that l-alanine, glycine, l-arginine and sodium chloride depress Tmgo, conceivably because of specific inhibition of an enzyme, or because of competition for a carrier system. Evidence in favor of a carrier sYstem was adduced by Berglund, Helander and Howe (18), who demonstrated in the dog muttual competitive inhibition between sulfate and thiosulfate reabsorption.…”

Section: Methodsmentioning

confidence: 99%

Renal Mechanisms for the Excretion of Inorganic Sulfate in Man *

Becker¹,

Heinemann²,

Igarashi³

et al. 1960

J. Clin. Invest.

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The sulfur contained in plasma is derived from sulfalipids, sulfatides, amino acids, and glycoproteins as well as from ionizable inorganic sulfate. The plasma concentration of inorganic sulfate is partially determined by the kidneys, since the ion is freely filterable at the glomerulus (1, 2) and reabsorbed by the renal tubules. In dogs (3) the excretory processes have been fairly well defined and the tubular reabsorptive mechanism has been shown to be characterized by a maximal transfer rate (Tmso4). The present study was undertaken to ascertain if similar mechanisms are operating in man. To elucidate this problem, the filtered load, tubular reabsorption, and urinary excretion of inorganic sulfate were measured prior to and during the infusion of sodium sulfate solution. Further, the readily exchangeable sulfate mass was determined using isotope dilution techniques. The results of this study show that the tubular reabsorption of inorganic sulfate in man is limited by a maximal transfer rate (Tm). MATERIALS AND METHODSSubjects. The subj ects were convalescent patients without apparent cardiovascular, renal, or metabolic disorders, and healthy young adult volunteers. All subjects had been on an ordinary diet and were fasted 12 hours prior to the study. concentration and the inulinoid blank in urine and plasma. To measure the glomerular filtration rate (GFR) a priming dose of inulin, administered to raise the blood level to approximately 0.25 mg per ml, was followed by a sustaining infusion containing inulin in saline, delivered by a Bowman constant infusion pump at a rate of 1.0 ml per minute.After an appropriate equilibration time, at least two urine collection periods were obtained for measurement of control glomerular filtration and sulfate excretion. Five per cent sodium sulfate 1 was subsequently administered by a second constant infusion pump to insure an independent rate of infusion of 2 to 10 ml per minute. Throughout each study, which lasted for about 4 hours, blood samples were obtained and urine collections were made at intervals of 30 to 40 minutes. Complete urine collections were obtained by urethral catheterization and bladder washout with 20 ml of sterile distilled water followed by an equal volume of air.Analytical methods. Inulin was determined by Schreiner's (4) modification of the method of Roe, and inorganic sulfate was analyzed by the method of Power and Wakefield (5).Determtiniation of the exchangeable sulfate miass. The readily available inorganic sulfate mass was calculated as the product of the fasting plasma inorganic concentration (Pso,) and the simultaneously measured volume of distribution of radiosulfate (Vsmo4). The volume of distribution of radiosulfate was derived by dividing the total administered radioactivity by the plasma radioactivity at the time of injection (6). This latter value was obtained by extrapolating the exponential disappearance curve of the injected radiosulfate to zero time. No correction was made for urinary loss of radiosulfate during the equilibration time. A...

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“…Sulfate increases during pregnancy in mother and the fetus [25][26][27][28]. Sulfate is reabsorbed at the renal tubule, but thiosulfate is not, and is secreted at a more proximal site of the tubule [29]. Furthermore, Brazy and Dennis [30] and Dennis and Brazy [31] indicated that, in the rabbit kidney, thiosulfate, inhibited secretory and absorptive fluxes of sulfate.…”

Section: Discussionmentioning

confidence: 99%

“…It is secreted rapidly in the proximal tubule and when thiosulfate, endogenous or exogenous, is in excess, for example during gestation, it inhibits secretory and absorptive fluxes of sulfate [29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Gestational urinary hyperthiosulfaturia protects hypercalciuric normal pregnant women from nephrolithiasis

Yatzidis

2004

Int Urol Nephrol

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Urinary calcium excretion increases by 1-2-fold during gestation in normal, uncomplicated pregnant women. Hypercalciuria occurs in all trimesters and elevates urine supersaturation with regards to calcium oxalate. However, crystalluria has not been a frequent clinical finding and stone formation is not a common complication of pregnancy. To elucidate this discrepancy we measured various chemical entities (i.e. calcium, oxalate, uric acid, phosphorous, magnesium, citrate, sulfate and thiosulfate) in urine at the end of each trimester of 25 pregnant women. Twenty-five healthy women served as controls. Our observations show that endogenous thiosulfate, a natural component of urine, increased considerably during pregnancy to approximately 36, 38 and 40 microM/24 hour at the end of each three trimesters. One month after delivery, endogenous thiosulfaturia and hypercalciuria, in parallel, returned to initial normal values. Consequently, it seems that gestational hyperthiosulfaturia protects hypercalciuric normal pregnant women from the risk of nephrolithiasis.

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Inorganic sulfate and thiosulfate: transport and competition in renal tubules of the dog

Cited by 19 publications

References 0 publications

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Renal Mechanisms for the Excretion of Inorganic Sulfate in Man *

Gestational urinary hyperthiosulfaturia protects hypercalciuric normal pregnant women from nephrolithiasis

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