Plasma Oxalate Concentration and Renal Excretion of Oxalate in Man

1974 ◽  
Vol 46 (1) ◽  
pp. 61-73 ◽  
Author(s):  
A. Hodgkinson ◽  
R. Wilkinson
Keyword(s):  
Normal Subjects ◽  
Volume Of Distribution ◽  
Mean Value ◽  
Tubular Secretion ◽  
Clearance Ratio ◽  
Oxalate Concentration ◽  
Isotopic Method ◽  
Isotopic Methods ◽  
Renal Tubular ◽  
Normal Men

1. The concentration of oxalate in plasma was determined by an isotopic method involving the simultaneous measurement of [14C]oxalate activities in plasma and urine and the concentration of stable oxalate in the urine. 2. Plasma oxalate concentrations ranged from 1.3 to 1.6 μmol/l (11.8–14.3 μg/100 ml) in three normal men; in fifteen male patients with renal calcium oxalate stones the mean value was 1.73 μmol/l (15.6 μg/100 ml), SD = 0.55 μmol/l (4.98 μg/100 ml). 3. The renal clearance of [14C]oxalate ranged from 162 to 358 ml/min (mean = 249 ml/min) in the normal subjects and from 95 to 315 ml/min (mean = 201 ml/min) in the patients. A direct and statistically significant relationship was observed between the oxalate and creatinine clearances. 4. The oxalate/creatinine clearance ratio ranged from 1.42 to 2.60 (mean = 1.95) in the normal subjects and from 1.04 to 2.33 (mean = 1.76) in the patients, implying a net renal tubular secretion of oxalate. However, oxalate excretion was unaffected by probenecid, a drug known to inhibit the active tubular transport of organic anions. 5. Possible errors in the determination of plasma oxalate concentration and oxalate clearance by chemical and isotopic methods are discussed. 6. Intravenous administration of [14C]oxalate to eight subjects allowed estimations of the miscible oxalate pool [mean = 53.3 μmol (4.80 mg); SD = 18.7 μmol (1.68 mg)], the volume of distribution of [14C]oxalate (mean = 45.2% of body weight; SD = 5.65) and the biological half-life of [14C]oxalate (mean = 91.10 min; SD = 13.89).

scholarly journals Single nephron function of the lesser spotted dogfish, Scyliorhinus canicula, and the effects of adrenaline

1987 ◽  
Vol 129 (1) ◽  
pp. 265-278
Author(s):  
J. A. Brown ◽  
C. Green
Keyword(s):  
Glomerular Filtration ◽  
Renal Tubule ◽  
Mean Value ◽  
Tubular Secretion ◽  
Water Reabsorption ◽  
Scyliorhinus Canicula ◽  
Glomerular Filtrate ◽  
Single Nephron ◽  
Adrenaline Infusion ◽  
Renal Tubular

Function of the kidney and the nephron in the lesser spotted dogfish, Scyliorhinus canicula, was investigated by clearance, renal tubular micropuncture and ferrocyanide infusion techniques. 70% of the glomerular filtrate was reabsorbed within the renal tubule, producing slightly hypotonic urine. Glomeruli were: perfused and filtering (F); arterially perfused but not filtering (NF); or non-arterially perfused and hence not filtering (NP). Adrenaline reduced the proportion of filtering glomeruli from 94% to 70%. Despite this reduction, a marked overall glomerular diuresis occurred. Single nephron glomerular filtration rates (SNGFRs) ranged from 1.5 to 26 nl min-1 with a mean rate of 9.5 nl min-1 during control periods. Adrenaline elevated SNGFR to a mean value of 22.9 nl min-1 (range 2.4-64.6 nl min-1). Tubular fluid/plasma inulin concentration ratios (TF/Pin) indicated reabsorption of around 74% of the glomerular filtrate by the proximal segments. Comparison of TF/P and urine/plasma inulin concentrations (U/Pin) strongly suggests tubular secretion of water beyond the point of puncture. Adrenaline infusion appears to increase both proximal water reabsorption and distal tubular secretion.

Coordinate activation of the corticotropic axis by insulin-induced hypoglycemia: simultaneous estimates of β-endorphin, adrenocorticotropin and cortisol secretion and disappearance in normal men

1993 ◽  
Vol 128 (6) ◽  
pp. 521-528 ◽  
Author(s):  
Ali Iranmanesh ◽  
German Lizarralde ◽  
Johannes D Veldhuis
Keyword(s):  
Plasma Concentrations ◽  
Metabolic Stress ◽  
Fold Increase ◽  
Volume Of Distribution ◽  
Mean Value ◽  
Cortisol Secretion ◽  
Daily Production ◽  
Deconvolution Analysis ◽  
The Mean ◽  
Normal Men

In the present study, we investigated the coordinate kinetic response of the corticotropic axis to the acute metabolic stress of hypoglycemia by applying deconvolution analysis to adrenocorticotropin (ACTH), β-endorphin and cortisol concentration-time series generated in seven normal men after intravenous administration of insulin. Hypoglycemic stress resulted in a 22-fold increase in the mean plasma concentration of ACTH to a maximum of 77±15 pmol/l, in conjunction with a 7.5-fold increase in the mean plasma β-endorphin concentration, the maximal value of which was 96±11 pmol/l. Plasma cortisol concentrations increased by 2.6-fold with a mean value of 734±14 nmol/l. Maximal plasma ACTH and β-endorphin concentrations were preceded by discrete secretory bursts with peak amplitudes of 10.5±2.7 and 10.6±2.0 pmol·I−1·min−1 (20-fold and ninefold increases compared to control), respectively. The mass of ACTH released was 114±20 pmol/l (3.4-fold increase), which corresponds to a total amount of 1.25 μg (50% of daily production and 0.5% of reported pituitary stores), assuming a distribution volume of 40 ml/kg. A total amount of 4.4±0.7 mg of cortisol was released after insulin-induced hypoglycemia, based on a mean cortisol secretory mass of 1088±137 nmol/l and a presumed 11.3-1 volume of distribution. Deconvolution-based estimates of the endogenous half-lives of ACTH, β-endorphin and cortisol were 17±0.6, 22±1.7 and 65±5.3 min, respectively. In summary, deconvolution analysis revealed a rapid coordinate activation of ACTH, β-endorphin and cortisol secretion after hypoglycemic stress, which correlated closely but temporally preceded increases in the respective plasma concentrations. Our inference that only a small fraction of pituitary ACTH content is released during hypoglycemic stress emphasizes the large reserve capability of the pituitary corticotropes. The percentage response of adrenal gland to the metabolic stress of hypoglycemia was of lesser magnitude, possibly owing to the rate-limiting properties of cortisol biosynthesis. We conclude that kinetic responses of the hypothalamic—pituitary—adrenal axis to hypoglycemic stress exhibit exquisite temporal synchrony and manifest a marked reserve capacity.

Renal Handling of Creatinine in Nephrotic and Non-Nephrotic Patients

1970 ◽  
Vol 38 (5) ◽  
pp. 555-562 ◽  
Author(s):  
C. F. Anderson ◽  
D. M. Jaecks ◽  
H. S. Ballon ◽  
J. R. De Palma ◽  
R. E. Cutler
Keyword(s):  
Renal Function ◽  
Normal Subjects ◽  
Tubular Secretion ◽  
Inulin Clearance ◽  
Clearance Ratio ◽  
Renal Handling ◽  
Secretory Rate ◽  
Ureteral Catheterization ◽  
Iothalamate Clearance

1. The endogenous creatinine/GFR (inulin or free [57Co]cyanocobalamin or [125I]iothalamate) clearance ratios were determined in ninety-nine non-nephrotic patients and subjects and in sixteen nephrotic patients. The clearance ratios of the nephrotic patients were not significantly different from those of the non-nephrotic patients and normal subjects. 2. The clearance ratios increased as the GFR fell from 176 to below 15 ml/min, then decreased toward unity at lower GFR values. 3. In an attempt to explain this biphasic relationship, two further studies were performed. Endogenous creatinine/inulin and [14C]creatinine/inulin clearance ratios were simultaneously determined in seventeen additional patients. The [14C]creatinine/inulin clearance ratio was the larger of the two in all patients with a GFR greater than 15 ml/min. In another group of eight patients with unequal-sized kidneys, who were studied during bilateral ureteral catheterization, the endogenous creatinine/inulin clearance ratios were determined and found not to differ significantly. 4. The three studies suggest that there is significant tubular secretion of creatinine at all levels of renal function. The increasing clearance ratio of endogenous creatinine/GFR as the GFR decreases is not due to increased tubular secretion of creatinine nor a result of a difference in creatinine handling by diseased kidneys, but rather a reflection of the decreasing fraction of non-creatinine chromogen to the total creatinine chromogen. The smaller clearance ratio at a very low GFR would be expected if the maximal tubular secretory rate of creatinine was exceeded.

Effect of DIDS on renal tubular transport

1980 ◽  
Vol 238 (2) ◽  
pp. F99-F106
Author(s):  
F. J. Koschier ◽  
M. F. Stokols ◽  
J. M. Goldinger ◽  
M. Acara ◽  
S. K. Hong
Keyword(s):  
Transport System ◽  
Organic Anion ◽  
Tubular Secretion ◽  
Inulin Clearance ◽  
Clearance Ratio ◽  
Renal Cortical Slice ◽  
Anion Transport System ◽  
Renal Tubular ◽  
Renal Slice Transport ◽  
Perfused Kidney

Two stilbene derivates that had been used to covalently label the Cl- carrier in the erythrocyte were investigated for reactivity with the renal organic anion system. These compounds, 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) and (4,4'-diisothiocyano)-dihydrostilbene-2,2'-disulfonate (H2DIDS), were found to be potent inhibitors (Ki congruent to 35 microM) of p-aminohippurate (PAH) transport in the renal cortical slice without affecting tetraethylammonium (TEA) transport or tissue viability. During renal clearance studies performed in the perfused kidney, DIDS decreased the PAH/inulin clearance ratio to congruent to 1. When the possible renal transport of [3H]H2DIDS was investigated, the renal slice transport or binding of [3H]H2DIDS reached a slice-to-medium ratio of congruent to 6, and this accumulation was decreased by probenecid. In perfused kidney experiments, the [3H]H2DIDS/inulin clearance ratio was congruent to 0.8. Since probenecid reduced this clearance ratio to congruent to 0.5, there was the possibility that H2DIDS underwent tubular secretion. In conclusion, DIDS and H2DIDS interacted with the renal organic anion transport system, which indicated that these compounds were possible probes for this transport system.

The Renal Clearance of Oxalate in Normal Subjects and Patients with Primary Hyperoxaluria

1971 ◽  
Vol 41 (3) ◽  
pp. 213-218 ◽  
Author(s):  
H. E. Williams ◽  
Gloria A. Johnson ◽  
L. H. Smith
Keyword(s):  
Oxalic Acid ◽  
Creatinine Clearance ◽  
Renal Clearance ◽  
Primary Hyperoxaluria ◽  
Normal Subjects ◽  
Constant Infusion ◽  
Clearance Ratio ◽  
Oxalate Concentration

1. The renal clearance of oxalate was studied in six normal subjects and in two patients with primary hyperoxaluria utilizing a constant infusion of [14C]oxalic acid. 2. The [14C]oxalate clearance in normal subjects was between 101 and 217 ml/min with a range in the ratio of [14C]oxalate clearance to creatinine clearance of 1.33–2.09. 3. The oxalate clearance in two patients with primary hyperoxaluria was within the range found in the normal subjects. 4. This study does not confirm the previous report of a low oxalate/creatinine clearance ratio in man nor the finding of an elevated oxalate clearance in patients with primary hyperoxaluria. 5. Estimates of serum oxalate concentration based on these clearance values suggest that the serum oxalate concentration in normal subjects is less than 100 μg/100 ml.

Sex Differences in the Metabolism of Ethanol and Acetaldehyde in Normal Subjects

1984 ◽  
Vol 67 (4) ◽  
pp. 397-401 ◽  
Author(s):  
M. J. P. Arthur ◽  
A. Lee ◽  
R. Wright
Keyword(s):  
Sex Differences ◽  
Elimination Rate ◽  
Young Male ◽  
Normal Subjects ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Mean Value ◽  
The Mean ◽  
Ethanol Elimination ◽  
Apparent Volume Of Distribution

1. Blood ethanol and acetaldehyde concentrations were compared in normal young male and female subjects after intravenous infusion of 0.5 g of ethanol/kg body weight. 2. After the infusion was completed, females had significantly higher mean concentrations of blood ethanol than males, but a significantly lower apparent volume of distribution (Vd) of ethanol (0.56 ± 0.06 l/kg vs 0.68 ± 0.17 l/kg, P<0.05). There were no differences in ethanol elimination rate (EER) (females 1.78 ± 0.3 mmol h−1 kg−1; males 1.87 ± 0.41 mmol h−1 kg−1). The mean value of the areas under the acetaldehyde/time curves (AUC) were significantly greater for males (88.5 ± 26.4 μmol/l. h) than for females (58.6 ± 31.5 μmol/l. h, P<0.05). 3. Since the ethanol elimination rate was similar in both sexes, the observed differences in AUC for acetaldehyde may reflect the sex differences in metabolism of this substrate by the liver.

ÉTUDES IN VIVO SUR LE MÉTABOLISME DES ANDROGÉNES APRES ADMINISTRATION DE STÉROÏDES INHIBITEURS DE L'OVULATION

1965 ◽  
Vol 50 (1) ◽  
pp. 131-144 ◽  
Author(s):  
P. Mauvais-Jarvis ◽  
M. F. Jayle ◽  
J. Decourt ◽  
J. Louchart ◽  
J. Truffert
Keyword(s):  
Luteinizing Hormone ◽  
Urinary Excretion ◽  
Normal Subjects ◽  
Hormone Activity ◽  
Testosterone Production ◽  
Normal Men ◽  
Ethinyl Oestradiol

ABSTRACT Normal subjects and hirsute women with micropolycystic ovaries were treated with ethinyl-oestrenol + 3-methoxy-ethinyl-oestradiol (Lyndiol®), in view of studying the action of this compound on the production of androgens and on the urinary excretion of their metabolites. In normal men, the production of testosterone and the excretion of androsterone and aetiocholanolone are suppressed, whereas the excretion of other 17-ketosteroids and the production of dehydroepiandrosterone sulphate are unchanged. Moreover, the luteinizing hormone activity (LH) in plasma is depressed. It seems that the preparation inhibits specifically the testicular androgen production, by suppressing the hypothalamo-hypophyseal control of LH. Testosterone production and urinary 17-ketosteroid excretion are modified in the same way in women with Stein-Leventhal's syndrome. Physiopathological and therapeutical implications which come from these results are discussed.

Effect of acid lumen pH on potassium transport in renal cortical collecting tubules

1976 ◽  
Vol 230 (1) ◽  
pp. 239-244 ◽  
Author(s):  
JF Boudry ◽  
LC Stoner ◽  
MB Burg
Keyword(s):  
Mean Value ◽  
Potassium Transport ◽  
Sodium Absorption ◽  
Positive Voltage ◽  
Tubule Lumen ◽  
Potassium Secretion ◽  
Transepithelial Voltage ◽  
Renal Tubular ◽  
Collecting Tubules

In order to determine the effect of acid lumen pH on renal tubular potassium transport, cortical collecting tubules were dissected from rabbit kidneys and perfused in vitro. When the pH of the perfusate was lowered from 7.4 to 6.8, potassium secretion into the tubule lumen decreased by an average of 47%. The transepithelial voltage increased from a mean value of -32 mV (lumen negative) at pH 7.4 to -51 mV at PH 6.8. Net sodium absorption from the tubule lumen was essentially unchanged (5% mean decrease). Transepithelial voltage and potassium secretion returned to control values when the pH of the perfusate was raised to 7.4. Alterations in pH of the bath had no comparable effect on the transepithelial voltage, whether the bath pH was increased or decreased. We conclude that a decrease in the pH of the tubule fluid of itself inhibits active potassium secretion in this tubule segment, providing an additional explanation for the decrease in potassium excretion found in acidosis. The negative voltage (presumably caused by sodium absorption out of the lumen) is increased under these conditions, possibly because of reduction of a smaller counterbalancing positive voltage caused by potassium secretion into the lumen.

scholarly journals Quantification of Ligand PET Studies using a Reference Region with a Displaceable Fraction: Application to Occupancy Studies with [11C]-DASB as an Example

2011 ◽  
Vol 32 (1) ◽  
pp. 70-80 ◽  
Author(s):  
Federico E Turkheimer ◽  
Sudhakar Selvaraj ◽  
Rainer Hinz ◽  
Venkatesha Murthy ◽  
Zubin Bhagwagar ◽  
...  
Keyword(s):  
Specific Binding ◽  
Normal Subjects ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Accurate Estimation ◽  
Data Sets ◽  
Reference Region ◽  
Reference Tissue ◽  
Positron Emission ◽  
Definition Of

This paper aims to build novel methodology for the use of a reference region with specific binding for the quantification of brain studies with radioligands and positron emission tomography (PET). In particular: (1) we introduce a definition of binding potential BPD = DVR–1 where DVR is the volume of distribution relative to a reference tissue that contains ligand in specifically bound form, (2) we validate a numerical methodology, rank-shaping regularization of exponential spectral analysis (RS-ESA), for the calculation of BPD that can cope with a reference region with specific bound ligand, (3) we demonstrate the use of RS-ESA for the accurate estimation of drug occupancies with the use of correction factors to account for the specific binding in the reference. [11C]-DASB with cerebellum as a reference was chosen as an example to validate the methodology. Two data sets were used; four normal subjects scanned after infusion of citalopram or placebo and further six test—retest data sets. In the drug occupancy study, the use of RS-ESA with cerebellar input plus corrections produced estimates of occupancy very close the ones obtained with plasma input. Test-retest results demonstrated a tight linear relationship between BPD calculated either with plasma or with a reference input and high reproducibility.

Abstract 14035: Renal Tubular Secretion and Cardiac Distribution of Dofetilide is Dependent on MATE1 Function

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Muhammad Erfan Uddin ◽  
Yan Jin ◽  
Alice A Gibson ◽  
Ingrid M Bonilla ◽  
Cynthia A Carnes ◽  
...  
Keyword(s):  
Organic Cation ◽  
Tubular Secretion ◽  
Hek293 Cells ◽  
Delayed Rectifier ◽  
Organic Cation Transporters ◽  
Wild Type ◽  
Renal Tubular Secretion ◽  
Cation Transporters ◽  
Renal Tubular

Introduction: Dofetilide is a delayed rectifier potassium channel inhibitor used to treat patients with atrial fibrillation and flutter, and its use is associated with a risk of QT prolongation and Torsades de Pointes . The mechanisms involved in dofetilide’s renal tubular secretion and its uptake into cardiomyocytes remain unknown. Previously reported drug-drug interaction (DDI) studies suggest the involvement of organic cation transporters. Here, we investigated the contribution of organic cation transporters (OCT2 and MATE1) to the pharmacokinetics of dofetilide to gain insight into its DDI potential. Hypothesis: Based on known DDIs with dofetilide, we hypothesize that OCT2 and/or MATE1 play a key role in the inter-individual variability in pharmacokinetics and pharmacodynamics of dofetilide. Methods: In vitro and ex vivo transport kinetics of dofetilide were determined in HEK293 cells stably transfected with OCT2 or MATE1, and in isolated cardiomyocytes, respectively. In vivo studies were performed in wild-type, OCT2-, and MATE1-deficient mice (n=5) receiving dofetilide (5 mg/kg, p.o., 2.5 mg/kg, i.v.), with or without several contraindicated drugs. Dofetilide concentrations in plasma and urine were determined by UPLC-MS/MS. Results: In vitro studies demonstrated that dofetilide is a good substrate of MATE1 but not OCT2. Deficiency of MATE1 was associated with increased plasma concentrations of dofetilide and with a significantly reduced urinary excretion (3-fold in females and 5-fold in males, respectively). Dofetilide accumulation in cardiomyocytes was increased by 2-fold in MATE1-deficient females, and pre-incubation with the MATE1 inhibitor cimetidine significantly reduced dofetilide uptake in wild-type cardiomyocytes. Several contraindicated drugs listed in the dofetilide prescribing information, including cimetidine, ketoconazole, increased dofetilide plasma exposure in wild-type mice by >2.8-fold. Conclusion: Renal secretion of dofetilide is mediated by MATE1 and is highly sensitive to inhibition by many widely used prescription drugs that can cause clinically relevant DDIs. Deficiency of MATE1 also increases accumulation in the heart which may contribute to individual variation in response to dofetilide.

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