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The effects of mannitol diuresis on digoxin and phenobarbital handling by the kidney: implications for tubular reabsorption and secretion of the cardiac glycoside.

The effect of mannitol diuresis on the renal clearance of digoxin and phenobarbital was studied in dogs. Mannitol diuresis significantly increased the clearance of digoxin and the ratio digoxin: inulin clearances (from 0.7 +/- 0.2 to 1.1 +/- 0.25). The increase in phenobarbital: inulin clearance ratio was significantly higher than the increase in the digoxin: inulin clearance ratio (4.9 fold vs 1.66 fold) (p less than 0.005). Mannitol diuresis did not significantly affect inulin clearance, nor digoxin protein binding during the experimental period while there was a significant increase in PAH clearance. Significant correlations were found between urine flow rate and digoxin renal clearance or digoxin: inulin clearance ratio. The increase in the ratio drug: inulin clearance with diuresis correlated inversely with the initial ratio; animals with more predominant net reabsorption had a higher increase in ratio. These studies suggest that the mannitol-induced increase in digoxin clearance stems from a combination of increased renal blood flow enhancing digoxin secretion, and increased urine flow rate inhibiting its reabsorption. We conclude that urine flow rate and renal blood flow are important determinants of the renal clearance of digoxin, independent of GFR. Any study assessing the effect of pathophysiological states or drug interactions on digoxin renal clearance must control for these factors.

Animals↗

Pressure diuresis mechanism in the control of renal function and arterial pressure.

Precise knowledge of the interrelationships between arterial pressure and urinary excretion of sodium and water is crucial to understanding the long-term control of arterial pressure. Although increases in renal perfusion pressure have been known for more than 35 years to inhibit tubular reabsorption, the mechanism of this pressure diuresis response, the humoral or physical factors involved, and even the nephron segments in which the changes in tubular function occur remain relatively unknown. This review focuses on the experimental evidence that supports current hypotheses concerning the mechanism of pressure diuresis. Specifically, it examines the possibility that pressure diuresis is caused by a small increase in glomerular filtration rate, alterations in the humoral or physical factors regulating proximal tubular reabsorption, and/or inhibition of tubular reabsorption in deep nephrons secondary to changes in hemodynamics in juxtamedullary nephrons. The concept originally proposed that the kidney serves as the dominant long-term controller of arterial pressure is largely based on the assumptions that the pressure diuresis phenomenon exists and that it occurs via a nonadaptive mechanism. It has been proposed that hypertension can develop only if the relationship between arterial pressure and sodium excretion is shifted toward higher pressures. The remainder of this review examines recent evidence indicating that an abnormality in the pressure natriuresis relationship may be associated with the development of hypertension in humans and in the genetic rat models of the disease.

Absorption↗

Atrial volume receptors. Demonstration of an effective "threshold" of left atrial distension by an inflated balloon to induce increased diuresis in the anesthetized dog.

1. The intraatrial balloon technique was used to study the effect of distension of the left atrium on the urinary flow of anesthetized dogs. The balloon was inflated with 0.3, 0.4 or 0.5 ml saline/kg body weight, respectively, in three experimental groups, each containing 10 mongrel dogs. Intraatrial pressure, arterial blood pressure, ECG and respiratory excursions were continuously monitored in all experiments. Urine flow, inulin and p-aminohippuric acid clearance, urine osmolarity, total sodium and total potassium excretion were measured during the control period, after inflation of the balloon and 30 min after deflation. 2. Left atrial distension with 0.3 ml/kg caused essentially no increase in diuresis. Inflation with 0.4 ml/kg induced a 60% increase of mean urinary flow with respect to the control period. Inflation with 0.5 ml/kg elicited a mean increase in diuresis of 110%. 3. When it occurred, increased diuresis was accompanied by a decrease of urine osmolarity that was compatible with a decrease of antidiuretic hormone activity, and by an increase in total sodium excretion. There were no statistically significant changes in glomerular filtration rate and effective renal plasma flow. 4. The demonstration of a "threshold" for the distension of the left atrium that is capable of inducing diuresis in the anesthetized dog and of overcoming strong opposing hemodynamic effects provides additional indirect evidence for the role of the left atrial stretch receptors in the regulation of body fluid volume.

Anesthesia↗

Diuresis renography and parenchymal transit times in the assessment of renal pelvic dilatation.

A comparison has been made between the results of diuresis renography and deconvolution analysis of the renogram in 36 patients (46 kidneys) with urographically demonstrated renal pelvic dilatation. The mean transit times obtained by deconvolution analysis of the parenchymal renograms of eight normal volunteers had a mean value of 2.8 + 0.6 (S.D.) min, and the upper limit of normal was thus established as 4 min. Twenty-two of 29 kidneys (76%) with nonobstructive diuresis renograms had parenchymal mean transit times of 4 min or below. Fourteen out of 17 kidneys (82%) with obstructive diuresis renograms had parenchymal mean transit times above 4 min. Both investigations may contribute to the noninvasive assessment of dilated renal pelves; the parenchymal retention function (quantified by mean transit time) assesses the effects of dilatation on tubular transit and renal function, whereas the diuresis renogram is a more specific test for evaluating impedance to flow.

Diuresis↗

Volume expansion enhances the recovery of renal function and prolongs the diuresis and natriuresis after release of bilateral ureteral obstruction: a possible role for atrial natriuretic peptide.

Plasma atrial natriuretic peptide (ANP) levels are elevated in patients with bilateral ureteral obstruction (BUO). To further evaluate the role of ANP in postobstructive diuresis, natriuresis and recovery of renal function, 3 groups of dogs were studied: Group 1, 6 dogs that underwent 48 hours of unilateral ureteral obstruction (UUO); Group 2, 6 dogs that underwent 48 hours of BUO; and Group 3, 6 dogs volume replete with normal saline during 48 hours of BUO. All 3 groups underwent hourly hemodynamic and clearance studies for 15 hours after the release of obstruction. Group 1 experienced no increase in either urine output or sodium excretion from the ipsilateral or contralateral kidney after release of obstruction. Groups 2 and 3 both experienced an initial diuresis and natriuresis after BUO (p < 0.01). However, in Group 2 diuresis and natriuresis after BUO ceased at 5 and 2 hours, respectively, while in Group 3 both persisted for 10 and 9 hours, respectively. Before obstruction the GFR was similar in all three groups. In Group 1 the GFR decreased significantly in the ipsilateral kidney (34.5 +/- 1.4 to 14.48 +/- 1.5 ml. per minute, (p < 0.01)) and increased significantly in the contralateral kidney (32.4 +/- 2.8 to 44.4 +/- 2.0 ml. per minute, (p < 0.05)) and remained so throughout the postobstruction period. The GFR in Groups 2 and 3 decreased to a similar level 1 hour after release (13.3 +/- 1.7 and 17.5 +/- 3.4 ml. per minute, respectively); however, Group 2 remained decreased during the period after release while group 3 increased to 23.4 +/- 3.4 ml. per minute (p < 0.01) at 11 hours after release of obstruction. In Group 2 the control plasma ANP level was 17.9 +/- 3.7 pg./ml. and was not altered by BUO, whereas ANP increased significantly after 48 hour BUO in Group 3, from 30.6 +/- 6.7 to 63.7 +/- 11.7 pg./ml. (p < 0.01). Before and after 48 hours of BUO, the pulmonary capillary wedge pressure was 5.0 +/- 2.0 mm. Hg and 7.0 +/- 1.0 mm. Hg (NS) in Group 2, while it increased from 7.18 +/- 1.5 mm. Hg to 11.6 +/- 1.9 mm. Hg (p < 0.01) in Group 3. We conclude that volume expansion during BUO enhances postobstructive diuresis and natriuresis and allows a greater recovery of GFR after release of the obstruction. This effect may be mediated through elevated plasma levels of ANP as measured in this study.

Animals↗

Opiate receptors within the blood-brain barrier mediate kappa agonist-induced water diuresis.

Data suggest that kappa opioid agonist-induced water diuresis involves inhibition of vasopressin (AVP) secretion; however, it is not clear whether this action involves kappa receptors in the neurohypophysis or receptors behind the blood-brain barrier (BBB). We have investigated the site of action using three selective kappa agonists, BRL 52656 (S(-)-2-(1-pyrrolidinylmethyl)-1-(4-trifluoromethylphenyl) acetyl piperidine hydrochloride), BRL 53114 ((-)-1-(4-trifluoromethylphenyl) acetyl-2-(1-pyrrolidinymethyl)3,3- dimethyl piperidine hydrochloride) and BRL 52974 (4-(1-pyrrolidinylmethyl)5-(3,4-dichlorophenyl)acetyl-4,5,6,7-t etrahydroimidazo [4,5-c] pyridine), with varying abilities to cross the BBB. Chemical and functional assays indicate that BRL 52974 has limited ability to cross the BBB, whereas BRL 53114 and BRL 52656 can freely penetrate. BRL 52974 was significantly less potent than BRL 52656 and BRL 53114 in causing a water diuresis in conscious rats. The ED10S (i.v. doses to cause a positive free water clearance of 10 microliters/min.100 g) for BRL 52974, BRL 52656 and BRL 53114 were 181, 9 and 3.4 mg/kg, respectively. Furthermore, in dogs BRL 52656 and BRL 53114 but not BRL 52974 (30 micrograms/kg i.v.) were able to cause a significant water diuresis. The data demonstrate that opiate receptors behind the BBB are primarily involved in kappa agonist-induced water diuresis and possibly inhibition of AVP secretion.

Animals↗

Challenging consults: application of principles of physiology and biochemistry to the bedside. Osmotic diuresis: the importance of counting the number of osmoles excreted.

Polyuria is usually the result of a water diuresis or an osmotic diuresis. Traditionally, the assessment of the extracellular fluid (ECF) volume and the concentration of Na+ in plasma is sufficient to differentiate between the two. We present a case and our approach, which is based on calculations and quantitation of osmoles, to demonstrate the utility of this approach. A patient with diabetes mellitus, human T-cell lymphocyte virus, type 1 (HTLV-1) associated lymphoma, and hypercalcemia presented with marked ECF volume contraction and polyuria. A spot urine osmolality was 567 mOsm/kg H2O in the face of urine output of approximately 6 L/d. The initial diagnosis was an osmotic diuresis. However, a quantitative analysis revealed the enormous number of osmoles could not be accounted for physiologically. Hence, we postulated a water diuresis to be the cause of the polyuria. To confirm this hypothesis, we found that at different times during his hospitalization, the urine specific gravity ranged from 1.005 to 1.022, and urine output varied markedly over 8-h periods. Despite a plasma sodium of 147 mmol/L, the patient did not complain of thirst. Taken together, this suggested the presence of a hypothalamic lesion which caused central diabetes insipidus with variable output of antidiuretic hormone together with a blunted thirst response. Illustration of the utility of a quantitative approach to polyuria is the focus of the discussion.

Chlorides↗

Dynamics of upper urinary tract. II. An electrophysiologic in vivo study of renal pelvis in pigs: analysis of the modality of pelvic activity during normal hydration and diuresis.

Renal pelvic function of Danish Landrace pigs under anesthesia was analyzed during "normal" and forced diuresis. Measurements were made of intrapelvic pressures, electromyogram recordings were taken from the pelvis and ureter, and bolus formation was followed. During constant diuresis, pelvic activity displayed a dominant frequency which varied between individuals. When pressure rose or fell, pelvic activity increased or decreased in proportion to the speed rather than the extent of the pressure change. Thus, after furosemide administration urine flow increased and pelvic pressure rose; and in association with the pressure rise, pelvic activity increased significantly when mean pelvic activity in the phase of steep pressure rise was compared with the mean activity over the last 5 min of the observation period before induction of diuresis. Thereafter, pelvic activity decreased despite maintenance of a higher pressure plateau than that in the initial low diuresis observation period. This mode of function can be explained by reference to the characteristics of smooth muscle. Postulation of a specific pacemaker is unnecessary.

Animals↗

Complications of diuresis in the alcoholic patient with ascites: a controlled trial.

Forty-three patients with decompensated alcoholic liver disease and ascites of recent onset were randomized to salt and water restriction alone (control group) or to salt and water restriction plus diuretics (diuresis group). The two treatment groups were comparable in clinical findings and laboratory results. Seven patients in the control group and 5 patients in the diuresis group died during the acute illness. Weight loss was more marked and the disappearance of ascites more common in those given diuretics. A modest decrease in serum sodium and increase in serum potassium, and readily reversible elevations of blood urea nitrogen were noted in the diuresis group. Eight patients in each treatment group developed either the hepatorenal syndrome, marked electrolyte abnormalities, or encephalopathy. Diuresis can be accomplished in these critically ill patients without serious complications that can be attributed to the diuretic treatment.

Alcoholism↗

"Well-tempered" diuresis renography: its historical development, physiological and technical pitfalls, and standardized technique protocol.

Differentiating the various causes of hydronephrosis from that of obstruction can be very difficult. Diuretic renography has been adopted as a noninvasive clinical management tool to assist in this differentiation. However, the correlation of the results of diuresis renography, the Whitaker test, and the surgical results has only been between 40% and 85%. This is believed to be due to the many physiological factors and technical pitfalls of the technique. These include variable renal function, variable compliance of the collecting system, the effect of back pressure from a full bladder, the state of hydration, the choice of radiopharmaceutical, and the timing of the diuretic injection. Even the technique of measuring the clearance half-time (T 1/2) is controversial, with at least eight different methods defined. In order to diminish the effect of these variables, a standardized protocol for diuretic renography has been proposed by a consortium of members of the Society for Fetal Urology and the Pediatric Nuclear Medicine Club of the Society of Nuclear Medicine. These include a standardized hydration with a dilute glucose solution, bladder catheterization and measurement of urine output response, uniform radiopharmaceutical choice, and diuretic dose with specific timing of the diuretic injection. The various methods for T 1/2 calculation are illustrated, and various stereotypical renogram and diuresis response curves are offered as aids in the interpretation of the study. Diuresis renography is one of the most complex functional studies in nuclear medicine today. A thorough understanding of the physiological basis for diuresis renography and the pitfalls of the technique is required for its appropriate use in the management of patients suspected of urinary tract obstruction.

Diuretics↗

Sensitivity of 131I-hippuran diuresis renography and pressure flow study (Whitaker test) in upper urinary tract obstruction.

Diuresis renography and pressure flow studies were performed in 14 patients with unilateral hydronephrosis. Based upon the results of intravenous pyelography, typical symptomatology, and the outcome of surgical treatment, all patients were found to have upper urinary tract obstruction. It was therefore possible to calculate the sensitivity of the two tests. Obstruction was found at the pressure flow studies in 7 of 14 patients (50%), while an obstructive pattern was found at diuresis renography in 12 of 13 patients (92%). Due to a very low glomerular filtration rate, diuresis renography was equivocal in 1 case. Based upon these results, diuresis renography seems to be superior to pressure flow studies in cases with upper urinary tract obstruction.

Adult↗

Sodium orthovanadate diuresis in rats.

The renal actions of differing doses of sodium orthovanadate were studied in conscious and anesthetized female Wistar rats. In conscious rats, sodium orthovanadate was given by i.v. or i.p. injections or by mouth. The most pronounced renal effects were seen after a 5 mg/kg i.p. injection of sodium orthovanadate. Urine flow and sodium excretion increased approximately 400% and urine osmolality fell from 1108 to 549 mOsmol/kg . H2O. Higher doses of sodium orthovanadate (20, 30 and 50 mg/kg) injected i.p. did not cause diuresis and were toxic. In anesthetized rats undergoing a 0.9% NaCl diuresis, i.v. infusion of sodium orthovanadate at a dose of 5 mg/kg/hr significantly increased urine flow and the excretion of sodium, calcium, phosphorus, sulfur, magnesium and chlorine, whereas glomerular filtration rate was unaltered. In anesthetized rats undergoing a water diuresis, i.v. infusion of sodium orthovanadate (5 mg/kg/hr) markedly reduced free-water clearance, indicating that this compound inhibits tubular reabsorption of sodium and chloride in diluting nephron segments. Blood and renal tissue levels of vanadium, measured using emission spectrographic analysis, in rats infused with sodium orthovanadate were 4 times higher than the concentration of sodium orthovanadate (1--10 microM) needed to inhibit 50% of the Na-K-adenosine triphosphate activity of rat renal homogenates in vitro. These data suggest that sodium orthovanadate produces diuresis at least in part by inhibiting Na-K-adenosine triphosphatase and solute transport in the distal nephron, likely the ascending limb of the loop of Henle.

Administration, Oral↗

Osmotic diuresis and its effect on total electrolyte distribution in plasma and urine of the aglomerular teleost, Lophius americanus.

Quantitative evaluations have been made of the chief anions and cations in plasma, urine, and pericardial fluid taken both from freshly captured goosefish and from those undergoing "laboratory diuresis." Measurements included: Na, K, Ca, Mg, Cl, SO(4), PO(4), protein, HCO(3), NH(3), pH, titratable acidity, freezing point depression, creatine, trimethylamine oxide, and plasma volume. The total patterns of electrolyte distribution in these body fluids are presented. The morphologically undifferentiated aglomerular tubule acts as a barrier to the free diffusion of monovalent electrolytes, while transporting actively the divalent ions, especially Mg. Urine taken from freshly captured fish is hypotonic to plasma, low in electrolyte, and as much as 50 per cent of its total osmolarity is accounted for by nitrogenous components. Of these creatine is transported most actively by the renal tubule cells. With the onset of diuresis immediately after capture, plasma osmolarity slowly rises and urine suddenly becomes isotonic with plasma as chloride floods into the urine. The active movement of Mg continues during diuresis and urine/plasma concentration ratios of 100 or more are sustained for days while the animals are kept in the laboratory. Na follows chloride and never reaches 50 per cent of plasma values, and K never appears in urine in more than mere traces. Electrolytes in this system are viewed as not being in true equilibrium but rather as constituting a biological steady state with the distribution across renal cells being maintained against passive diffusion by the expenditure of cellular energy.

Animals↗

Quantitative effects of osmotic diuresis following angiographic contrast administration.

Osmotic diuresis resulting from the administration of angiographic contrast poses the potential threat of marked volume losses obligated by the renal excretion of non-reabsorbable solute. We prospectively assessed urinary excretion of solute and water following cardiac angiography in 14 euvolemic subjects without preexisting renal disease, by a protocol that allowed each patient to serve as his own control. During the initial 6 h after the beginning of angiography, contrast administration resulted in increased total osmolar excretion from a control rate of 0.79 +/- 0.09 to 1.09 +/- 0.09 mOsm/min (P less than .05) with a return to control values thereafter. Surprisingly, sodium, potassium, and chloride excretion rates did not differ significantly from control values. After subtraction of the molar contribution of electrolytes, urea, and creatinine from the total osmolar excretion rate, it was apparent that the "residual osmolar excretion rate" of 0.48 +/- 0.05 mOsm/min was markedly elevated over the control value of 0.11 +/- 0.05 mOsm/min (P less than .01), reflecting the excretion of contrast agent. Despite the marked osmotic diuresis, urine output during this period (3.9 +/- 0.2 cc/min) did not differ significantly from the control value of 4.0 +/- 0.3 cc/min. We conclude that marked volume losses are not a necessary concomitant of contrast-induced osmotic diuresis in the euvolemic cardiac patient without renal disease.

Adult↗

Visualization and quantification of renal R2* changes during water diuresis.

PURPOSE: To refine and evaluate methods for analysis of renal blood oxygenation level dependent (BOLD) MRI data. MATERIALS AND METHODS: Color R2* maps and regions-of-interest (ROIs) on the borderline between cortex and medulla were applied to renal BOLD MRI data of a group of 13 young female subjects. RESULTS: The distribution of R2* within the kidneys was heterogeneous and the response of human kidneys to water diuresis was patchy. R2* values at the cortico-medullary border region have a smaller variation than in wider cortical or medullary regions and are sensitive to physiological changes produced by water diuresis. CONCLUSION: These methods provide improved visualization of the regional distribution of R2* and its variations and more precise quantification of the changes in renal R2* produced by water diuresis.

Adult↗

Effect of diuresis on urinary erythrocyte morphology in glomerulonephritis.

The differentiation between glomerular and non-glomerular haematuria by phase-contrast microscopy has proved to be a useful tool in the diagnosis of glomerulonephritis. In an attempt to evaluate the effect of marked diuresis on the altered red cell morphology in patients with biopsy proven glomerulonephritis, urinary sediments were examined following water or furosemide-induced diuresis. In both diuretic states urine flow increased, urine osmolality decreased and the percentage of glomerular erythrocytes was significantly reduced in the urinary sediment. These data demonstrate that the alteration in urinary red cells in glomerulonephritis is mainly caused by tubular forces. The diagnostic significance is reduced during increased diuresis and the evaluation of urinary red cell morphology should not be performed.

Adult↗

Shortcomings of diuresis scintigraphy in evaluating urinary obstruction: comparison with pressure flow studies.

BACKGROUND: In at least 15 % of dilated urinary tracts, diuresis renography fails to assess the presence or absence of urinary obstruction. OBJECTIVE: To determine the shortcomings of (99 m)Tc-DTPA frusemide diuresis renography by reference to pressure flow studies. MATERIALS AND METHODS: Thirty-four patients, aged 1 month to 20 years, with questionable obstruction were evaluated by diuresis renography and pressure flow studies (the Whitaker test) as the reference method during the same short period of time. Discrepancies were analysed. RESULTS: In patients with type I or IIIa renographic response, pressure flow studies never led to any change in management. Poor function, major dilatation and prior surgery were found to be risk factors of inaccurately obstructive pattern (type II) on renography (n = 6). In patients with type IIIb response, pressure flow studies could show low-grade (n = 3) or intermittent obstruction (n = 2). Intermittent obstruction was also demonstrated in two patients with type II response. CONCLUSION: In patients with risk factors, type II response was sometimes inaccurate, and urodynamic evaluation showed absence of obstruction and led to conservative management. Type IIIb response should be considered equivocal rather than partially obstructive, and pressure flow studies could be considered in such patients.

Adolescent↗

Trypanosoma cruzi in the rectum of the bug Triatoma infestans: effects of blood ingestion of the vector and artificial diuresis.

The population density and the percentage of different developmental stages of an established infection of Trypanosoma cruzi were determined at 40 days after the last feeding of the fourth instar in the rectum (lumen, anterior and posterior wall) of fed and unfed groups of fifth instars of Triatoma infestans. Additionally, the rectum and the Malpighian tubules were incubated in saline, inducing diuresis by addition of the diuretic hormone. The rectum contained an average of 200,000-400,000 T. cruzi. After feeding the percentages of spheromastigotes and drop-like intermediate stages were reduced from < 7% and 15%, respectively, to < 3%, but those of slender intermediate stages increased statistically significantly from < 7% to 10%. After 4 h of diuresis the in-vitro-incubated isolated rectum with the four Malpighian tubules showed the same trends, indicating that diuresis rather than factors of the hemolymph or digestive products induces the development of metacyclic trypomastigotes of T. cruzi originating from epimastigotes.

Animals↗