scholarly journals Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate

2018 ◽  
Vol 105 (5) ◽  
pp. 1187-1195 ◽  
Author(s):  
Jill C. Chappell ◽  
P. Kellie Turner ◽  
Y. Anne Pak ◽  
James Bacon ◽  
Alan Y. Chiang ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Tubular Secretion ◽  
Renal Tubular Secretion ◽  
Renal Tubular

scholarly journals Effect of Probenecid on the Renal Excretion Mechanism of a New Carbapenem, DA-1131, in Rats and Rabbits

1999 ◽  
Vol 43 (1) ◽  
pp. 96-99 ◽  
Author(s):  
So H. Kim ◽  
Won B. Kim ◽  
Myung G. Lee
Keyword(s):  
Body Weight ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Renal Excretion ◽  
Anion Transport ◽  
Tubular Secretion ◽  
Renal Secretion ◽  
Renal Tubular Secretion ◽  
Transport Inhibitor ◽  
Renal Tubular

ABSTRACT The effects of probenecid, an anion transport inhibitor, on the renal excretion mechanism of a new anionic carbapenem, DA-1131, were investigated after a 1-min intravenous infusion of DA-1131 at 100 mg/kg of body weight to rabbits and 50 mg/kg to rats with or without probenecid at 50 mg/kg for both species. In control rabbits, the renal clearance (CLR) of DA-1131 and the glomerular filtration rate based on creatinine clearance (CLCR) were 6.14 ± 2.09 and 2.26 ± 0.589 ml/min/kg, respectively. When considering the less than 10% plasma protein binding of DA-1131 in rabbits, renal tubular secretion of DA-1131 was observed in rabbits. The CLR of DA-1131 (3.87 ± 0.543 ml/min/kg) decreased significantly with treatment with probenecid in rabbits, indicating that the renal tubular secretion of DA-1131 was inhibited by probenecid. However, in control rats, the CLR of DA-1131 (5.80 ± 1.94 ml/min/kg) was comparable to the CLCR(4.29 ± 1.64 ml/min/kg), indicating that DA-1131 was mainly excreted by glomerular filtration in rats. Therefore, it could be expected that the CLR of DA-1131 could not be affected by treatment with probenecid in rats; this was proved by a similar CLR of DA-1131 with treatment with (6.93 ± 0.675 ml/min/kg) or without (5.80 ± 1.94 ml/min/kg) probenecid. Therefore, the renal secretion of DA-1131 is a factor in rabbits but is not a factor in rats.

scholarly journals Simultaneous Measurement of Glomerular Filtration Rate, Effective Renal Plasma Flow and Tubular Secretion in Different Poultry Species by Single Intravenous Bolus of Iohexol and Para-Aminohippuric Acid

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1027
Author(s):  
Lenka Stroobant ◽  
Siska Croubels ◽  
Laura Dhondt ◽  
Joske Millecam ◽  
Siegrid De Baere ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Simultaneous Measurement ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Tubular Secretion ◽  
Effective Renal Plasma Flow ◽  
High Dose ◽  
Potential Marker

The aim of the current study was to investigate the simultaneous measurement of plasma p-aminohippuric acid (PAH) clearance as a potential marker to assess effective renal plasma flow (eRPF) and tubular secretion (TS), and the plasma clearance of iohexol (IOH) as a marker of the glomerular filtration rate in poultry species. The PAH was administered intravenously (IV) to broiler chickens, layers, turkeys, Muscovy ducks, and pigeons. Each animal received successively a single bolus dose of 10 mg PAH/kg bodyweight (BW) and 100 mg PAH/kg BW to assess the eRPF and TS, respectively. Simultaneously with both PAH administrations, a single IV bolus of 64.7 mg/kg BW of IOH was administered. A high linear correlation (R2 = 0.79) between eRPF, based on the clearance of the low dose of PAH, and BW was observed for the poultry species. The correlation between TS, based on the clearance of the high dose of PAH, and BW was moderate (R2 = 0.50). Finally, a moderate correlation (R2 = 0.68) was demonstrated between GFR and eRPF and between GFR and TS (R2 = 0.56). This presented pharmacokinetic approach of the simultaneous administration of IOH and PAH enabled a simultaneous evaluation of eRPF/TS and GFR, respectively, in different poultry species.

scholarly journals P27 The juvenile pig as animal model for unraveling renal drug elimination processes in children

2019 ◽  
Vol 104 (6) ◽  
pp. e28.1-e28
Author(s):  
L Dhondt ◽  
S Croubels ◽  
P De Paepe ◽  
P De Cock ◽  
M Devreese
Keyword(s):  
Animal Model ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Tubular Secretion ◽  
Tubular Reabsorption ◽  
Drug Elimination ◽  
Renal Drug Elimination

BackgroundOver the years pigs were promoted as potential animal model for humans due to their high degree of anatomical and physiological similarities with humans. Gasthuys et al. demonstrated that the maturation of the kidney function in terms of the glomerular filtration rate (GFR) in growing pigs was comparable to humans, but no data are currently available on renal plasma flow, renal tubular secretion and reabsorption.1 The aim of this pilot study was to unravel the contribution of distinct renal elimination processes in juvenile pigs and to compare with reported human values.MethodsEight seven-week-old pigs were intravenously administered a single bolus of a cocktail of following renal markers: iohexol (64.7 mg/kg body weight (BW), GFR), para-aminohippuric acid (PAH, 10 mg/kg BW, effective renal plasma flow (ERPF) and anion secretion), pindolol (0.05 mg/kg BW, cation secretion) and fluconazole (0.5 mg/kg, tubular reabsorption). Plasma and urinary concentrations were determined for PAH, pindolol and fluconazole at several time points. Only plasma concentrations were assessed for iohexol. PK modelling was performed with Phoenix® WinNonlin®.ResultsThe clearance of iohexol was 97.9 ± 16.1 ml/min/m² (mean ± SD). The ERPF, calculated as the renal clearance of PAH, was 9.5 ± 2.1 ml/min/kg. These GFR and ERPF values are approximately a factor 1.3 higher than the values observed in humans, namely 63.5–75.0 mL/min/m² and 6.5 ± 2.0 mL/min/kg.2,3 The net tubular secretion of PAH was 5.4 ± 1.8 mL/min/kg, which was comparable with the values obtained in humans (5.0 ± 1.8 mL/min/kg).3 Results for cation secretion and tubular reabsorption are not yet available (to be presented at the congress).ConclusionThe net tubular secretion of PAH was comparable between the juvenile pigs and humans. The GFR and ERPF were generally a factor 1.3 higher in juvenile pigs compared to humans.ReferencesGasthuys E., et al., Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research. Frontiers in Pharmacology 2017. 8.Schwartz GJ, Furth SL. Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatric Nephrology 2007;22(11):1839–1848.Gross AS, et al., Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol. British Journal of Clinical Pharmacology 2001. 51(6):547–555.Disclosure(s)This study was funded by the Special Research Fund of Ghent University (BOF16/DOC/285).

Renal Excretion of l-Epinephrine in the Dog

1958 ◽  
Vol 193 (2) ◽  
pp. 371-374 ◽  
Author(s):  
Richard T. Jones ◽  
William D. Blake
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Excretion ◽  
Renal Plasma Flow ◽  
Blocking Agent ◽  
Tubular Secretion ◽  
Sodium Pentobarbital ◽  
Tubular Transport

The renal excretion of epinephrine was studied in dogs anesthetized with sodium pentobarbital. Epinephrine in plasma and urine was quantitatively estimated by the fluorometric method of Lund. Glomerular filtration rate (creatinine clearance), renal plasma flow (PAH clearance) and PAH transport were employed as parameters of renal function. During periods of intravenous infusion of epinephrine, the percentage of hormone excreted was about 4.6% of that infused. The renal clearance of epinephrine was significantly greater than the glomerular filtration rate though less than renal plasma flow. From this and other information it was concluded that epinephrine is excreted both by tubular transport (tubular secretion) and glomerular filtration. The tubular transport of epinephrine was not inhibited by either 2,4-dinitrophenol or an adrenergic blocking agent.

Renal Tubular Protein Degradation of Radiolabelled Aprotinin (Trasylol) in Patients with Chronic Renal Failure

1993 ◽  
Vol 85 (6) ◽  
pp. 733-736 ◽  
Author(s):  
R. Rustom ◽  
J. S. Grime ◽  
P. Maltby ◽  
H. R. Stockdale ◽  
M. J. Jackson ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Chronic Renal Failure ◽  
Glomerular Filtration ◽  
Normal Renal Function ◽  
Filtration Rate ◽  
Renal Uptake ◽  
The Mean ◽  
Renal Tubular

1. The new method developed to measure renal tubular degradation of small filtered proteins in patients with normal renal function, using radio-labelled aprotinin (Trasylol) (R. Rustom, J. S. Grime, P. Maltby, H. R. Stockdale, M. Critchley, J. M. Bone. Clin Sci 1992; 83, 289–94), was evaluated in patients with chronic renal failure. 2. Aprotinin was labelled with either 99mTc (40 MBq) or 131I (0.1 MBq), and injected intravenously in nine patients, with different renal pathologies. 51Cr-EDTA clearance (corrected for height and weight) was 40 + 5.4 (range 11.2-81) ml min−1 1.73 m−2. Activity in plasma and urine was measured over 24–48 h, and chromatography on Sephadex-G-25-M was used to separate labelled aprotinin from free 99mTcO4− or 131I−. Renal uptake was measured for 99mTc-labelled aprotinin only. 3. The volume of distribution was 20.2 + 2.3 litres. Chromatography showed all plasma activity as undegraded aprotinin, and urine activity only as the free labels (99mTcO4− or 131I−). 4. As in patients with normal renal function, activity in the kidney appeared promptly, with 5.7 + 2.5% of the dose detected even at 5 min. Activity rose rapidly to 9.4 + 1.6% of dose after 1.5 h, then more slowly to 15.0 + 0.5% of dose at 4.5 h, and even more slowly thereafter, reaching 24.1 + 2.8% of dose at 24 h. Extra-renal uptake was again insignificant, and both 99mTcO4− and 131I− appeared promptly in the urine, with similar and uniform rates of excretion over 24 h. 5. Both tubular uptake at 24 h and the rate of tubular metabolism over 24 h were lower than in the patients with normal renal function studied previously, but only the rate of tubular metabolism was directly related to the glomerular filtration rate (r = 0.75, P <0.02). 6. Correction for the reduced glomerular filtration rate yielded values for both tubular uptake (0.67 + 0.14 versus 0.32 + 0.03% of dose/ml of glomerular filtration rate, P <0.005), and tubular metabolism (0.033 + 0.07 versus 0.015 + 0.001% of dose h−1 ml−1 of glomerular filtration rate, P <0.005) that were higher by comparison with those for patients with normal renal function studied previously. 7. Fractional renal degradation of 99mTc-aprotinin (in h−1), derived from the mean rate of urinary excretion of the free isotope over a given interval, divided by the mean cumulative kidney uptake over the same interval, also fell steeply early, and then more slowly to 0.07 + 0.01 h−1 at 14.25 h (between 4.5 and 24 h). 8. It is concluded that the method described previously is also suitable in patients with chronic renal failure, allowing further research into renal disease progression.

Effect of Iopentol on Renal Function and its Use for Calculation of Glomerular Filtration Rate in Children

1995 ◽  
Vol 36 (1) ◽  
pp. 64-68
Author(s):  
G. Stake ◽  
T. Monclair ◽  
K. J. Berg ◽  
K. Rootwelt ◽  
O. Brekke
Keyword(s):  
Alkaline Phosphatase ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Diagnostic Yield ◽  
Clinical Importance ◽  
Ionic Contrast ◽  
Urine Concentrations ◽  
Ionic Contrast Medium ◽  
Renal Tubular

Nineteen children received 99mTc-DTPA for renography. The next day they received a simultaneous injection of the non-ionic contrast medium iopentol for urography and another injection of 99mTc-DTPA. The glomerular filtration rate (GFR) was estimated from the plasma elimination of 99mTc-DTPA as well as iopentol. Serum concentrations of creatinine and β2-microglobulin, and urine concentrations of creatinine, β2-microglobulin, alkaline phosphatase, N-acetyl-glucosaminidase, and albumin were determined. A significant reduction (12 ± 3%) of GFR was observed after the injection of iopentol, without a subsequent rise in serum creatinine or β2-microglobulin. The urinary excretion of albumin and β2-microglobulin remained unchanged, while the excretion of alkaline phosphatase and N-acetyl-glucosaminidase was significantly increased after the urography, indicating some tubular effects of iopentol. Iopentol caused few and mild adverse events, the diagnostic yield was high, and the small changes in the renal tubular function parameters are presumed to be without clinical importance. The observed depressive effect on the GFR demands further investigations before iopentol can be recommended as a GFR-marker in children.

Feed intake, digestion, and renal function in Merino sheep selected for higher clean fleece weight

1998 ◽  
Vol 49 (1) ◽  
pp. 107 ◽  
Author(s):  
G. J. Faichney ◽  
R. J. Welch ◽  
G. H. Brown
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Feed Consumption ◽  
Control Line ◽  
Urea Synthesis ◽  
Feed Digestibility ◽  
Fleece Weight ◽  
Renal Tubular

Two-year-old ewes from 2 Merino lines selected for higher clean fleece weight were compared with their control line when given a lucerne hay diet and a lower quality diet of mixed wheaten and lucerne hays. There were no differences between lines in voluntary feed consumption, feed digestibility, urea synthesis and excretion, or renal function. Voluntary feed consumption, digestibility, urea synthesis and excretion, glomerular filtration rate, and urea and creatinine clearances were higher on the higher quality lucerne hay diet; renal tubular function was not affected by diet. Water intake was higher in the selection lines; consequently, these sheep produced more of a less concentrated urine. The renal clearance of endogenous true creatinine was significantly greater than the glomerular filtration rate, indicating that creatinine was secreted in the kidney tubules. The results support the conclusion that differences between selection lines in physiological parameters not directly associated with wool follicle function are unlikely to be consistent enough to be useful predictors of genetic merit for fleece weight.

Renal Clearance of Fluoride in Children and Adolescents

PEDIATRICS ◽  
1985 ◽  
Vol 75 (3) ◽  
pp. 575-579
Author(s):  
Carl-Johan Spak ◽  
Ulla Berg ◽  
Jan Ekstrand
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Free Water ◽  
Tubular Secretion ◽  
Urinary Flow ◽  
Water Diuresis ◽  
Free Water Clearance ◽  
Clearance Technique

Renal function and fluoride excretion have been studied in 38 children. The children were divided into three groups according to their glomerular filtration rate: normal (92 to 136 mL/min/1.73 m2 of body surface area [BSA]), low (&lt; 92 mL/min/1.73 m2 BSA, and super-normal (&gt; 136 mL/min/1.73 m2 BSA). Standard clearance technique with infusion of inulin and p-aminohippuric acid during water diuresis was used. Mean renal fluoride clearance was 45.0 ± 9.8 (SD) mL/min in the group of children with normal glomerular filtration rates and 31.4 ± 8.8 mL/min in the group with low glomerular filtration rates. This difference was statistically significant. There was a close linear relationship between renal fluoride clearance and glomerular filtration rate, urinary flow, and free water clearance. The fractional fluoride excretion did not differ between the groups. About 60% of the filtered fluoride was reabsorbed. No evidence for tubular secretion exceeding the reabsorption could be found. The results suggest that children have lower renal fluoride clearance rates than adults and indicate that a moderate impairment of the renal function could lead to increased retention of fluoride.

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