Urinary Excretion of Bile Acids in Cholestasis: Evidence for Renal Tubular Secretion in Man

1981 ◽  
Vol 61 (6) ◽  
pp. 773-780 ◽  
Author(s):  
C. L. Corbett ◽  
T. C. Bartholomew ◽  
Barbara H. Billing ◽  
J. A. Summerfield

1. the apparent renal clearance of intravenously injected [14C]glycocholate and [3H]-chenodeoxycholate-3-sulphate was estimated in 22 patients with cholestasis. the degree of protein binding of the isotopes in serum from these patients was determined. the effects of pharmacological agents, changes in urine flow rate and pH on renal clearance were studied. 2. the mean renal clearance of [14C]glycocholate was 1.7 ± 0.4 ml/min (mean ± sem), and that of [3H]chenodeoxycholate-3-sulphate was 6.4 ± 0.9 ml/min. [14C]Glycocholate was 80.1% protein bound and [3H]chenodeoxycholate-3-sulphate 96.5% protein bound. 3. Comparisons of the observed clearance rates with those calculated on the basis of glomerular filtration of the unbound fraction suggest that whereas [14C]glycocholate is predominantly reabsorbed by the renal tubules, [3H]chenodeoxycholate-3-sulphate appears in the urine mainly as the result of tubular secretion. 4. Probenecid, ethacrynic acid, frusemide and bendrofluazide decreased the clearance of both bile acids, implying competition for secretion via the proximal tubular organic acid secretory pathway between these compounds and bile acids. 5. Passive non-ionic diffusion does not seem to be an important mechanism in the renal excretion of bile acids as changes in urine flow rate and pH did not influence bile acid clearance. 6. A greater affinity of the proximal tubular organic acid secretory pathway for sulphated than for non-sulphated bile acids may explain the higher observed renal clearance rate of sulphated bile acids.

1976 ◽  
Vol 51 (1) ◽  
pp. 103-105
Author(s):  
D. F. Smith ◽  
M. Shimizu

1. Renal lithium clearance in healthy men was elevated while the subject was reclining, decreased upon standing and increased upon lying down during 45–60 min tests. 2. Parallel changes in renal clearance of creatinine, sodium and potassium, and urine flow rate occurred in response to the changes in posture. 3. The findings demonstrate for the first time that posture is a factor that can influence lithium excretion. Control of posture during lithium excretion tests is recommended.


2013 ◽  
Vol 304 (2) ◽  
pp. F137-F144 ◽  
Author(s):  
Scott C. Thomson ◽  
Ali Kashkouli ◽  
Prabhleen Singh

The incretin hormone glucagon-like peptide-1 (GLP-1) is released from the gut in response to fat or carbohydrate and contributes to negative feedback control of blood glucose by stimulating insulin secretion, inhibiting glucagon, and slowing gastric emptying. GLP-1 receptors (GLP-1R) are also expressed in the proximal tubule, and possibly elsewhere in the kidney. Presently, we examined the effect of a GLP-1R agonist on single-nephron glomerular filtration rate (GFR; SNGFR), proximal reabsorption ( Jprox), tubuloglomerular feedback (TGF) responses, and urine flow rate in hydropenic male Wistar and Wistar-Froemter rats. Micropuncture and whole-kidney data were obtained before and during infusion of the GLP-1 agonist exenatide (1 nmol/h iv). SNGFR and Jprox were measured by late proximal collection at both extremes of TGF activation, which was achieved by perfusing Henle's loop at 0 or 50 nl/min. Primary changes in Jprox were revealed by analysis of covariance for Jprox with SNGFR as a covariate. Effects on TGF activation were determined in a separate set of experiments by comparing early distal and late proximal collections. Exenatide increased SNGFR by 33–50%, suppressed proximal tubular reabsorption by 20–40%, doubled early distal flow rate, and increased urine flow rate sixfold without altering the efficiency of glomerulotubular balance, TGF responsiveness, or the tonic influence of TGF. This implies that exenatide is both a proximal diuretic and a renal vasodilator. Since the natural agonist for the GLP-1R is regulated by intake of fat and carbohydrate, but not by salt or fluid, the control of salt excretion by the GLP-1R system departs from the usual negative-feedback paradigm for regulating salt balance.


1972 ◽  
Vol 15 (4) ◽  
pp. 338-346 ◽  
Author(s):  
Herbert S. Diamond ◽  
Robert Lazarus ◽  
David Kaplan ◽  
David Halberstam

1962 ◽  
Vol 13 (2) ◽  
pp. 307 ◽  
Author(s):  
RL Reid

Acetone comprised 0–40% (average 18%) of the acetoacetic acid plus acetone fraction in sheep blood, in which the level of this fraction was 0.6–5.2 mg % (as acetone). Acetoacetic acid was largely converted to acetone during storage of blood at –20°C, with intermittent thawing for analysis. Concentrations of acetoacetic acid in red cells were similar to those in plasma, but those of ß-hydroxybutyric acid were considerably lower. In contrast to acetoacetic acid, ß-hydroxybutyric acid was virtually absent from foetal blood and from brain tissue. Concentrations of both ketone fractions in liver and muscle tissue were about one-half the blood concentrations. The renal clearance of acetoacetic acid plus acetone in hyperketonaemic pregnant ewes was independent of blood level up to 20 mg % and was little affected by rate of urine flow. Clearance values were in the range of 4–9 ml per min, which indicates that most of the acetoacetic acid filtered at the glomeruli is absorbed by the renal tubules. Renal clearance of ß-hydroxybutyric acid was dependent on blood level and was more affected by rate of urine flow than that of acetoacetic acid. Very little ß-hydroxybutyric acid appeared in the urine when blood levels were below 15 mg %. Clearance increased as blood concentration rose above this level, and reached maximum values, mostly of 3–5 ml per min, at blood levels exceeding 30 mg %.


1988 ◽  
Vol 254 (2) ◽  
pp. R357-R380 ◽  
Author(s):  
L. Rabinowitz ◽  
D. M. Green ◽  
R. L. Sarason ◽  
H. Yamauchi

In unanesthetized adult sheep, following intake of a daily meal, there was a peak in K excretion. The maximum and minimum rates of K excretion following meals were directly related to meal K content. On days without meals, no peak in K excretion occurred. Changes in K excretion on fed and fast days occurred without changes in the low levels of plasma aldosterone and were poorly correlated with urine or blood pH, urine flow rate, Na excretion, or the filtered load of K, but they correlated well with fractional K excretion. Plasma K did not change on fast days. Plasma K increased on some, but not all, fed days. Increases in plasma K that occurred on fed days were insufficient to account for the concurrent kaliuresis. Infusion of aldosterone or isotonic NaCl failed to alter K excretion in fed or fasted sheep. Infusion of isotonic NaCl + aldosterone hypertonic Na2SO4 + aldosterone increased K excretion in fasted but not fed sheep. Infusion of K in the rumen of fed and fasted sheep elevated rumen K concentration and led to increases in K excretion that could not be explained by increases in plasma K. The mechanisms responsible for the homeostatic changes in K excretion on fed and fast days were not ascertained but may importantly depend on sensors of enteric K content.


Author(s):  
Katja M. Gist ◽  
Jamie Penk ◽  
Eric L. Wald ◽  
Laura Kitzmiller ◽  
Tennille N. Webb ◽  
...  

AbstractA standardized, quantified assessment of furosemide responsiveness predicts acute kidney injury (AKI) in children after cardiac surgery and AKI progression in critically ill adults. The purpose of this study was to determine if response to furosemide is predictive of severe AKI in critically ill children outside of cardiac surgery. We performed a multicenter retrospective study of critically ill children. Quantification of furosemide response was based on urine flow rate (normalized for weight) measurement 0 to 6 hours after the dose. The primary outcome was presence of creatinine defined severe AKI (Kidney Disease Improving Global Outcomes stage 2 or greater) within 7 days of furosemide administration. Secondary outcomes included mortality, duration of mechanical ventilation and length of stay. A total of 110 patients were analyzed. Severe AKI occurred in 20% (n = 22). Both 2- and 6-hour urine flow rate were significantly lower in those with severe AKI compared with no AKI (p = 0.002 and p < 0.001). Cutoffs for 2- and 6-hour urine flow rate for prediction of severe AKI were <4 and <3 mL/kg/hour, respectively. The adjusted odds of developing severe AKI for 2-hour urine flow rate of <4 mL/kg/hour was 4.3 (95% confidence interval [CI]: 1.33–14.15; p = 0.02). The adjusted odds of developing severe AKI for 6-hour urine flow rate of <3 mL/kg/hour was 6.19 (95% CI: 1.85–20.70; p = 0.003). Urine flow rate in response to furosemide is predictive of severe AKI in critically ill children. A prospective assessment of urine flow rate in response to furosemide for predicting subsequent severe AKI is warranted.


1983 ◽  
Vol 105 (1) ◽  
pp. 351-362 ◽  
Author(s):  
A. J. MCVICAR ◽  
J. C. RANKIN

1. Improved estimates of urine flow rates of lampreys in various salinities were obtained by the collection of urine for periods of up to 48 h from minimally-stressed, unanaesthetized fish, following catheterization of the urinogenital papilla. 2. The mean urine flow rate of freshwater lampreys was 200.7 ±14.3 ml kg−1 day−1. 3. Urine flow in freshwater lampreys was correlated with spontaneous changes in gill ventilation rate. MS222 anaesthesia reduced both ventilation and urine flow rates, but pronounced effects were only observed at concentrations greater than those needed to induce light anaesthesia (50–55 mg 1−1). Urine flow rate in unanaesthetized fish was extremely sensitive to rapid (6°Ch−1) changes in temperature and Q10 (6–16°C) was approximately 5. 4. Urine flow rate decreased rapidly as the osmotic difference between the body fluids and environment approached zero, and the rate of flow in 30% seawater lampreys was only 7.6% that of freshwater fish. 5. There was no evidence for an effect of environmental calcium concentration on branchial osmotic permeability. 6. Extensive tubular reabsorption of ions occurred in freshwater lampreys. The total daily excretion rate of sodium ions generally decreased in salinities hyperosmotic to the plasma, indicating enhanced reabsorption, but secretion of magnesium and sulphate ions was greatly increased. Urine osmolarity was significantly increased in lampreys in hyperosmotic salinities. 7. Present data compare favourably with data obtained previously from anaesthetized animals, indicating that renal function in lampreys is not significantly impaired by light MS222 anaesthesia.


1995 ◽  
Vol 7 (5) ◽  
pp. 1311 ◽  
Author(s):  
EM Wintour ◽  
R Riquelme ◽  
C Gaete ◽  
C Rabasa ◽  
E Sanhueza ◽  
...  

Samples of maternal and fetal plasma, fetal urine, and amniotic fluid were collected from 8 chronically cannulated pregnant llamas, in the last third of gestation. The samples were obtained for up to 18 days post-surgery. Osmolality, sodium (Na), potassium (K), chloride (Cl), and urea were measured on 40 samples collected on days 1, 2, 3, 4-5, 6-7, 8-9, and 10-19. The osmolalities of maternal and fetal plasma, fetal urine and amniotic fluid, averaged over these 7 time periods, were, respectively, 312 +/- 2, 311 +/- 1, 484 +/- 14, and 317 +/- 1 mosmol kg-1. Values are given as mean +/- s.e. The major differences from fetal fluid values in the ovine fetus (from previously published values) were the higher osmolality and urea concentration of llama fetal urine. Urine flow rate measured in 6 fetuses, 4.5-6.5 kg body weight, was 5.8 +/- 0.4 mliter h-1; urea clearance rate was 55.5 +/- 11.8 mliter h-1. Glomerular filtration rate (GFR), measured with 51Cr-EDTA in 5 fetuses on 1-4 occasions, was 111.4 +/- 23.3 mliter h-1. Fractional reabsorptions (FR) of Na, K and Cl were 97.9 +/- 1, 75.9 +/- 13.5 and 97.7 +/- 0.4% respectively. The GFR (25 mliter kg-1 h-1) and urine flow rate (1 mL kg-1 h-1) were less than half and about one-tenth the respective values in ovine fetuses. As Na reabsorption is the major oxygen-consuming activity of the kidney, the llama fetal kidney requires only half the oxygen needed by the ovine fetal kidney to reabsorb the filtered sodium load. The reason for the formation of hypertonic, rather than hypotonic, urine in the fetal llama may be due to both greater morphological maturity of the kidney and the excretion of as yet unidentified osmotically active organic substances.


1986 ◽  
Vol 251 (3) ◽  
pp. R639-R642 ◽  
Author(s):  
D. W. Duff ◽  
K. R. Olson

Dorsal aortic pressure (DAP), urine flow rate, and urinary K+, Na+, and Cl- were monitored in chronically catheterized unanesthetized rainbow trout before and after injection of saline, tissue extracts, or synthetic (rat, Ile-26) atrial natriuretic factor (ANF). Synthetic ANF (1.0 and 10.0 micrograms/kg body wt) and extracts from trout atria and ventricles increased DAP, urine flow rate, and electrolyte excretion. Saline, skeletal muscle extracts, and 0.1 microgram/kg body wt synthetic ANF had no effect on DAP and only minor effects on renal water and ion excretion. The slow-onset long-duration pressor response to ANF and heart extracts contrasted with a rapid short-acting pressor effect of epinephrine. Synthetic ANF (10 micrograms/kg body wt) and ventricular extracts produced marked increases in Na+ and Cl- excretion but only a mild diuresis. Much of the increase in urine flow rate appears to be due to solvent injection. These results show that trout hearts contain an ANF-like material and that mammalian and piscine ANF produce hemodynamic and renal effects upon intra-arterial injection.


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