INACTIVATION OF ARGININE-VASOPRESSIN BY THE ISOLATED PERFUSED RABBIT KIDNEY

1974 ◽  
Vol 62 (1) ◽  
pp. 1-10 ◽  
Author(s):  
J. LEVI ◽  
S. ROSENFELD ◽  
C. R. KLEEMAN
Keyword(s):  
Plasma Flow ◽  
Arginine Vasopressin ◽  
Renal Plasma Flow ◽  
Tubular Reabsorption ◽  
Extraction Ratio ◽  
Rabbit Kidney ◽  
Plasma Samples ◽  
Filtered Load ◽  
Anaesthetized Rat ◽  
Blood Reservoir

SUMMARY The ability of the kidney to extract (inactivate and excrete) argininevasopressin (AVP) from the blood was studied in the isolated perfused rabbit kidney. AVP was added to the blood reservoir to give an initial approximate concentration of 100 μu./ml plasma and samples were taken simultaneously from the arterial and venous side at 5, 15, 30 and 45 min. The AVP concentration in the plasma samples was determined by bioassay in the water-loaded, ethanol-anaesthetized rat. The clearance (extraction ratio x renal plasma flow) of AVP from the blood was concentration-dependent. The average extraction ratio ranged from 0·25 at levels of 100 to 44 μu./ml plasma and 0·42 at levels of 44 to 19 μu./ml plasma. The excretion of AVP in the urine was 23% and 29% respectively of the calculated filtered load, in two isolated perfused kidneys, indicating tubular reabsorption and/or tissue inactivation of the filtered hormone.

Cross-circulation study of natriuretic factors in rats with reduced nephron mass

1978 ◽  
Vol 235 (5) ◽  
pp. F465-F472
Author(s):  
D. R. Wilson ◽  
U. Honrath
Keyword(s):  
Renal Insufficiency ◽  
Plasma Flow ◽  
Chronic Renal Insufficiency ◽  
Renal Plasma Flow ◽  
Tubular Reabsorption ◽  
Sham Operation ◽  
Electrolyte Excretion ◽  
Humoral Factors ◽  
Clearance Studies ◽  
Initial Clearance

The importance of humoral factors, including urea, in the adaptations in electrolyte excretion which occur with acute or chronic reduction in nephron mass was studied using isovolemic cross-circulation in 38 pairs of anesthetized rats. After initial clearance studies, donor rats with acute (48 h) three-quarter nephrectomy or sham operation, acute urea loading, or chronic (2–3 wk) three-quarter nephrectomy or sham operation, underwent cross-circulation with normal recipient animals. Donor rats with acute three-quarter nephrectomy caused a marked natriuresis-kaliuresis in normal recipients. Natriuresis resulted from inhibition of tubular reabsorption independent of changes in GFR or renal plasma flow. Urea was a major but not the only factor involved in the cross-circulation natriuresis-kaliuresis. The severity of reduction in nephron mass, as indicated by the GFR of the donor rat, correlated with the increase in electrolyte excretion in the recipient. Donor rats with chronic three-quarter nephrectomy produced a slight but significant natriuresis in recipients which was much less than that seen with acute three-quarter nephrectomy. Since the GFR and blood urea nitrogen level of donors with acute and chronic renal insufficiency were similar, it was evident that the chronicity of reduced nephron mass, through mechanisms that are not clear, had a significant effect on the level of circulating natriuretic and kaliuretic factors in renal insufficiency.

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).

scholarly journals Rapid microplate method for PAH estimation

2002 ◽  
Vol 283 (2) ◽  
pp. F236-F241 ◽  
Author(s):  
Rajiv Agarwal ◽  
Keyword(s):  
Renal Clearance ◽  
Plasma Flow ◽  
Coefficient Of Variation ◽  
Renal Plasma Flow ◽  
Hplc Method ◽  
Plasma Samples ◽  
Limits Of Agreement ◽  
Average Ratio ◽  
Red Color ◽  
The Cost

Evaluation of renal hemodynamics requires estimation of effective renal plasma flow, which is commonly measured by the renal clearance of p-aminohippuric acid (PAH). There are many existing methods for PAH assay that are complicated, expensive, or time consuming. We describe a rapid, precise, and accurate microplate-based assay of PAH using p-dimethylaminocinnamaldehyde, which produces a red color on reaction with PAH, and compare it with a reference HPLC method. Renal PAH clearances were measured in 10 volunteers, and clearances were calculated by using the new and HPLC methods. There was excellent agreement between the HPLC and the microplate method of PAH assay. The average ratio of microplate to HPLC method was nearly 1.0, and the limits of agreement (2 SD) for plasma, urine, and clearances were 17.2, 19.3, and 25.5%, respectively. Intraday coefficient of variation for urine and plasma was <7%; interday coefficient of variation was <6% for urine and plasma samples. The microplate method is a reliable alternative to a reference HPLC method and can be performed for a fraction of the cost, time, and reagents.

Effects of Hyperventilation and Hypocapnic/Normocapnic Hypoxemia on Renal Function and Lithium Clearance in Humans 

1998 ◽  
Vol 89 (6) ◽  
pp. 1389-1400 ◽  
Author(s):  
Niels Vidiendal Olsen ◽  
Henrik Christensen ◽  
Tom Klausen ◽  
Niels Fogh-Andersen ◽  
Inger Plum ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Face Mask ◽  
Tubular Reabsorption ◽  
Effective Renal Plasma Flow ◽  
Arterial Oxygen ◽  
The Face ◽  
Proximal Tubular ◽  
Proximal Tubular Reabsorption

Background Using the renal clearance of lithium as an index of proximal tubular outflow, this study tested the hypothesis that acute hypocapnic hypoxemia decreases proximal tubular reabsorption to the same extent as hypocapnic normoxemia (hyperventilation) and that this response is blunted during normocapnic hypoxemia. Methods Eight persons were studied on five occasions: (1) during inhalation of 10% oxygen (hypocapnic hypoxemia), (2) during hyperventilation of room air leading to carbon dioxide values similar to those with hypocapnic hypoxemia, (3) during inhalation of 10% oxygen with the addition of carbon dioxide to produce normocapnia, (4) during normal breathing of room air through the same tight-fitting face mask as used on the other study days, and (5) during breathing of room air without the face mask. Results Hypocapnic and normocapnic hypoxemia and hyperventilation increased cardiac output, respiratory minute volume, and effective renal plasma flow. Glomerular filtration rate remained unchanged on all study days. Calculated proximal tubular reabsorption decreased during hypocapnic hypoxemia and hyperventilation but remained unchanged with normocapnic hypoxemia. Sodium clearance increased slightly during hypocapnic and normocapnic hypoxemia, hyperventilation, and normocapnic normoxemia with but not without the face mask. Conclusions The results indicate that (1) respiratory alkalosis with or without hypoxemia decreases proximal tubular reabsorption and that this effect, but not renal vasodilation or natriuresis, can be abolished by adding carbon dioxide to the hypoxic gas; (2) the increases in the effective renal plasma flow were caused by increased ventilation rather than by changes in arterial oxygen and carbon dioxide levels; and (3) the natriuresis may be secondary to increased renal perfusion, but application of a face mask also may increase sodium excretion.

Renal functions and urea handling in pregnant and lactating Corriedale ewes

1996 ◽  
Vol 76 (3) ◽  
pp. 469-472 ◽  
Author(s):  
M. N. Rodriguez ◽  
I. Tebot ◽  
A. Le Bas ◽  
C. Nievas ◽  
A. Cirio ◽  
...  
Keyword(s):  
Key Words ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Late Pregnancy ◽  
Fractional Excretion ◽  
Urea Clearance ◽  
Renal Functions ◽  
Pregnancy And Lactation ◽  
Filtered Load

Renal urea conservation was evaluated in Corriedale ewes during late pregnancy and lactation. Glomerular filtration, renal plasma flow and urea clearance were significantly reduced both states compared with control sheep. Filtered load of urea and urine urea elimination were significantly reduced during lactation (−46% and −45%, respectively, vs. controls). No changes were noted in fractional excretion of urea. Therefore, Corriedale ewes restrict urine urea losses during lactation by reducing glomerular filtration. During late pregnancy, urea sparing is less marked. Key words: Renal functions, urea, pregnancy, lactation, sheep

Clinical Renal Function Testing by External Double Isotope Monitoring Technique

1971 ◽  
Vol 10 (01) ◽  
pp. 16-24
Author(s):  
J. Fog Pedersen ◽  
M. Fog Pedersen ◽  
Paul Madsen
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Correlation Coefficients ◽  
Feedback System ◽  
Effective Renal Plasma Flow ◽  
Advantages And Disadvantages

SummaryAn accurate catheter-free technique for clinical determination simultaneouslyof glomerular filtration rate and effective renal plasma flow by means of radioisotopes has been developed. The renal function is estimated by the amount of radioisotopes necessary to maintain a constant concentration in the patient’s blood. The infusion pumps are steered by a feedback system, the pumps being automatically turned on when the radiation measured over the patient’s head falls below a certain preset level and turned off when this level is again readied. 131I-iodopyracet was used for the estimation of effective renal plasma flow and125I-iothalamate estimation of the glomerular filtration rate. These clearances were compared to the conventional bladder clearances and good correlation was found between these two clearance methods (correlation coefficients 0.97 and.90 respectively). The advantages and disadvantages of this new clearance technique are discussed.

RENAL FUNCTION AND KIDNEY SIZE FOLLOWING HYPOPHYSECTOMY IN MAN

1965 ◽  
Vol 48 (3) ◽  
pp. 348-354 ◽  
Author(s):  
Thomas Falkheden ◽  
Ingmar Wickbom
Keyword(s):  
Renal Function ◽  
Diabetic Retinopathy ◽  
Glomerular Filtration Rate ◽  
Plasma Flow ◽  
Mammary Carcinoma ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Kidney Weight ◽  
Kidney Size ◽  
Before And After

ABSTRACT Measurements of glomerular filtration rate (GFR) and renal plasma flow (RPF) were performed in close connection with roentgenographic estimation of kidney size, before and after hypophysectomy, in 10 patients (four cases of metastatic mammary carcinoma, five cases of diabetic retinopathy and one case of acromegaly). Hypophysectomy was regularly followed by a decrease in GFR and RPF. In most cases, a reduction in the roentgenographic kidney size was also observed. However, the changes in the roentgenographic kidney size and calculated kidney weight after hypophysectomy were smaller and occurred at a slower rate than the alterations in GFR and RPF. The results favour the view that, primarily, the decrease in GFR and RPF following hypophysectomy is essentially functional rather than due to a reduced kidney mass.

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