Osmotic Clearance Research Articles

The renal response of sheep to intraportal infusion of glucagon.

The effects on renal functions of infusing glucagon (100 ng kg-1 min-1) into the portal vein system were studied in young anaesthetized sheep kept on a diet with normal protein and digestible energy contents. The clearance measurements of the left kidney functions showed a decreased urine flow rate (from 0.36 +/- 0.04 to 0.18 +/- 0.03 ml min-1; P < 0.01) within the first 10 min of glucagon infusion, falling to 0.07 +/- 0.02 ml min-1 (P < 0.01) during the next 10 min. The glomerular filtration rate also decreased from 17.56 +/- 2.92 ml min-1 to its lowest value, 3.34 +/- 1.02 ml min-1, (P < 0.01) after 20 min of glucagon infusion. Decreases in urea excretion (from 53.1 +/- 6.46 to 3.82 +/- 1.27 mumol min-1; P < 0.01) and osmotic clearance (from 0.67 +/- 0.13 to 0.09 +/- 0.02 ml min-1; P < 0.01) occurred during the first 20 min. The plasma level of glucose increased from 4.01 +/- 0.53 to 8.33 +/- 1.12 mmol l-1 (P < 0.05) 20 min after the start of glucagon infusion. Twenty minutes after the start of glucagon infusion, the values of all the parameters measured began to recover, although they did not reach the control level, even after 1 h. Blood pressure was stable during the whole experiment. The results show that the effects of intraportally infused glucagon on kidney functions in sheep are the opposite of those obtained from similar experiments in laboratory animals with simple stomachs or in humans.

Effect of Urea and Indomethacin Intake on Solute Excretion in the Syndrome of Inappropriate Secretion of Antidiuretic Hormone

Our purpose was to compare the effect of urea and indomethacin on solute excretion in hyponatremic patients with inappropriate secretion of antidiuretic hormone (SIADH). In 6 patients (serum Na: 126 +/- 3 mmol/l), the intake of urea (0.1 g/kg) induced a decrease in sodium excretion while urine osmolality, urine flow and osmotic clearance (Cosm) did not change. In the control group, the urinary flow and Cosm were increased as expected, while sodium excretion tended to increase. In the SIADH group, the decrease in the fractional excretion (FE) of Na+ (FE.Na+) (or FE.Cl-) after urea intake was negatively correlated with urinary urea concentration while the FE.K+ was positively correlated with FE.Na+ (or FE.Cl-), which suggests that the effect of urea on sodium excretion takes place proximally to the distal tubule, probably at the thin ascending limb. After indomethacin intake, FE.Na+ (or FE.Cl-), FE.K+, Fe.osm and Fe.urea decreased in the normal and hyponatremic groups. The mean free water reabsorption relatively to osmolar delivery was lower in SIADH (p < 0.05), and did not change significantly after indomethacin intake. The fact that the decrease of FE.Na+ (or FE.Cl-) after indomethacin was associated with a decrease in FE.K+ suggests that the increase in sodium (or chloride) reabsorption occurred more proximally to the distal tubule (probably a the medullary segment of the thick ascending limb of the loop of Henle).

Renal tubular function in horses during submaximal exercise

Exercise-induced changes in renal function were examined during steady-state submaximal treadmill exercise in six unfit mares. Horses were randomly assigned to either an exercise or parallel control (no exercise) trial on day 1 and the alternate trial 1 wk later. The mares ran on a treadmill, set at a 6 degrees incline, for 1 h at 55-60% of maximal heart rate. Exercise significantly (P less than 0.05) increased plasma osmolality, plasma [K+], urine flow (+ 45%), Na+ excretion (+ 371%), K+ excretion (+ 57%), osmotic clearance (+ 32%), Na+ clearance (+ 391%), K+ clearance (+ 33%), and fractional Na+ excretion (+ 320%) and significantly decreased plasma [Cl-], Cl- excretion (-46%), Cl- clearance (-41%), and fractional Cl- excretion (-47%). Glomerular filtration rate, fractional K+ excretion, and free water clearance did not change during exercise. Atrial natriuretic peptide increased during exercise from 11 +/- 1 pg/ml at rest to a peak of 40 +/- 9 pg/ml (264%, P less than 0.05) at 40 min. Increases in plasma renin activity (66%, P less than 0.05) were accompanied by increases in plasma aldosterone concentration (760%, P less than 0.05). Vasopressin concentration increased (P less than 0.05) steadily over the 60-min period of exercise. It was concluded that, in horses, submaximal exercise-induced increases in urine flow and sodium excretion are associated with a concurrent increase in the plasma concentration of atrial natriuretic peptide.

Respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution in endotoxemic calves

Summary The respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution (hss) treatment were examined in 12 endotoxic, pentobarbitalanesthetized calves (8 to 20 days old). Escherichia coli endotoxin (055:B5) was infused iv at a rate of 0.1 μg/kg of body weight over 30 minutes. Endotoxin induced severe respiratory effects, with marked hypoxemia and increases in arterial-alveolar O2 gradient (P[A —a]O2), physiologic shunt fraction (Qs/Qt), and physiologic dead space to tidal volume ratio (Vd/Vt). Oxygen consumption was decreased, despite an increase in the systemic O2 extraction ratio. Peak effects were observed at the end of endotoxin infusion. The renal response to endotoxemia was characterized by a decrease in free-water reabsorption and osmotic clearance, as well as a decrease in sodium and phosphorus excretion. Endotoxemia induced leukopenia, thrombocytopenia, hyperphosphatemia, hypoglycemia, acidemia, and increased serum alkaline phosphatase concentrations. Calves were treated with hss (2,400 mosm/L of NaCl, 4 ml/kg, n = 4) or an equivalent sodium load of isotonic saline solution (iss; 300 mosm/L of NaCl, 32 ml/kg, n = 4) 90 minutes after the end of endotoxin administration. Both solutions were infused over a 4- to 6-minute period. A control group (n = 4&gt; was not treated. Infusion of hss or iss failed to induce a significant change in Pao2, P(A-a)o2, (Qs/Qt), (Vd/Vt), or oxygen consumption. Both solutions increased systemic oxygen delivery to above preendotoxin values. Hypertonic saline infusion induced significant (P &lt; 0.05) increases in serum Na and Cl concentrations and osmolality, whereas iss induced a significant increase in serum Cl concentration and a significant decrease in serum phosphorus concentration. Both hss and iss reversed the endotoxin-induced changes in renal function, with increases in free water reabsorption and osmotic clearance, as well as increases in sodium and phosphorus excretion. Sodium retention was greater following hss administration. On the basis of these findings, hypertonic saline solutions can be rapidly and safely administered to endotoxic calves.

Hormonal, electrolyte, and renal responses to exercise are intensity dependent

Previous work indicates that the magnitude and direction of renal responses to exercise depend on the exercise intensity. To examine mechanisms responsible for these findings, renal and hormonal responses were studied in eight healthy male subjects (29.6 +/- 1.9 yr) before and immediately after four 20-min bouts of submaximal exercise (cycle ergometry) at work loads representing 25, 40, 60, and 80% of maximal oxygen consumption. Urine flow, osmotic clearance, glomerular filtration rate, and sodium excretion (UNa+V) all tended to rise at the 25% work load but were markedly reduced at the higher work intensities. Changes in urine flow paralleled changes in glomerular filtration rate (r = 0.91). Plasma vasopressin (ADH), aldosterone, and plasma renin activity tended to increase progressively with increases in work load, with the increases for all hormones reaching statistical significance when the level of exercise reached greater than or equal to 60% of maximal oxygen consumption. However, atrial natriuretic peptide was elevated (P less than 0.05) at all work loads from greater than 1.6-fold of control levels at the 25% work load to greater than 7-fold at the 80% work load. The increase in urine flow (6 of 8 subjects) and UNa+V (7 of 8 subjects) may be due to the increase in atrial natriuretic peptide and/or a 10% suppression (P less than 0.05) of ADH at the 25% work load.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term hemodynamic effects of intravenous propionyl-L-carnitine in anesthetized dogs

The effects of intravenous administration of propionyl-L-carnitine (PLC) were investigated in anesthetized dogs instrumented for the analysis of general hemodynamic and electrocardiographic data, peripheral blood flows, coronary blood flow and oxygen consumption, urine flow, and renal function. PLC was administered in bolus (20, 60, and 200 mg/kg) or by infusion (20 mg/kg/min * 15 min or 30 mg/kg/min * 10 min). In some cases also L-carnitine (LC) and L-carnitine+propionate (LC + P) were administered in doses equimolar to those of PLC. PLC elicited dose-dependent, short-lasting enhancements of cardiac output, both in open- and closed-chest conditions. Arterial blood pressure, heart rate, and contractility varied slightly and unpredictably; the substance did not elicit electrocardiographic effects. These responses were not changed by alpha- or beta-adrenergic blockade, nor by the administration of a calcium antagonist, but they were abolished or reversed by the combination of such blocking interventions. Mesenteric and iliac blood flows were increased by both PLC and LC; LC + P increased these, and in addition increased renal blood flow. A strong diuresis obtained with PLC, LC, and LC + P was due to osmotic clearance following the administration of hyperosmotic solutions. PLC elicited coronary vasodilation with reduced oxygen extraction; this effect lasted longer than the general hemodynamic effects and was not seen with LC. All the cardiovascular actions of PLC can be attributed to its pharmacologic properties, rather than to its role as a metabolic intermediate.

The mechanism of polyethylene glycol-induced natriuresis in rats: Role of atrial natriuretic hormone

A putative role of atrial natriuretic hormone (ANH) in a polyethylene glycol (PEG) 200-induced natriuresis was examined in conscious Wistar rats. Low molecular weight PEG 200 (0.5 or 1.0 ml/100g body weight) was orally administered to rats by gavage. Urine was collected during a 3 hr test period and blood was obtained at the end of each experiment for measurement of ANH, PRA, clearance studies and for indirect indices of plasma volume. Urinary excretion of sodium and volume increased while plasma ANH concentrations were markedly decreased in a dose-related manner following PEG 200 administration. The osmotic clearance was also elevated following PEG 200 administration. No significant change was observed in any of the parameters following high molecular weight PEG 8000. The observed decrease in ANH was associated with an apparent contraction of plasma volume despite the increased serum osmolality. These data indicate that the ANH inhibitory influence of the decreased plasma volume takes precedence over the stimulatory effect of the hyperosmolality and the latter is primarily responsible for the increased osmotic clearance and natriuresis observed in this model.

Exercise training-induced hypervolemia in the horse

The purpose of this study was to determine if a chronic hypervolemia would accompany endurance exercise training in the horse. Six mature previously inactive horses were utilized for this study. During the 5-wk experiment, five of the horses were trained for 14 d on a treadmill ergometer at a constant treadmill speed of 5.6 km X hr-1 and a constant grade of 12.5% for graduated lengths of time. One horse was trained by lunging at a trotting pace in a round pen. Following training, plasma volume increased by 4.7 1 (29.1%, P less than 0.05). Although the rate of daily water intake did not change during the training period, 24-h urine output decreased by an average of 3.5 1 X d-1 (-24.5%, P less than 0.05). Resting glomerular filtration rate and the rate of sodium clearance were not altered by training. However, urea, potassium, and osmotic clearance were decreased by training (P less than 0.05) while free water clearance was increased (P less than 0.05). Resting plasma aldosterone and arginine vasopressin concentrations were not altered by training. Plasma potassium concentration was significantly decreased (P less than 0.05) following the 2 wk of training. These data would appear to suggest that renal control mechanisms affecting water reabsorption via the re-absorption of urea and osmotically active substances other than sodium provide the primary route for the training-induced hypervolemia seen in horses.

Exercise training-induced hypervolemia in greyhounds: role of water intake and renal mechanisms

The purpose of this study was to determine if the chronic hypervolemia that accompanies endurance exercise training is due only to an increase in the rate of water intake or if there were contributions from renal mechanisms. Four greyhound dogs, previously sedentary for 3 yr, were utilized. During the 28-day experiment each dog was trained on a treadmill ergometer for 14 consecutive days at 65% of its pretraining maximal work intensity. After training, plasma volume increased 472 ml (27.5%, P less than 0.05). The rate of water intake increased 328 ml/day (33%, P less than 0.05), whereas urine output increased 87 ml/day (20.8%, P less than 0.05). The mean resting 24-h values for clearance of sodium increased 0.29 ml/min (90.3%, P less than 0.05), and clearance of potassium decreased 1.51 ml/min (16.1%, NS). Glomerular filtration rate, free water clearance, and osmotic clearance were not significantly altered. These data suggest that the primary mechanism for the exercise training-induced hypervolemia in dogs is a net positive water balance via increased water consumption without significant contribution from an increase in renal water reabsorption.

Effect of simultaneous administration of glucagon and insulin on renal function in patients with liver cirrhosis and ascites.

Since glucagon and insulin (G/I) have been suggested to be hepatotrophic substances, the effect of G/I infusion on the ability to excrete water and sodium was tested in seven patients with cirrhosis and ascites (decompensated group), and compared with that in seven cirrhotics without ascites (compensated group). A constant infusion of 1 U glucagon and 10 U regular insulin over 2 hours daily for 14 days resulted in a significant improvement of prothrombin time in the decompensated group. Concomitantly, an increase in urine volume (62%, p less than 0.02) and a tendency toward an increase in urinary sodium excretion (68%, 0.05 less than p less than 0.1) were observed only in the decompensated group after the G/I infusion. In addition, these were associated with increases in creatinine clearance and osmotic clearance. These results suggest that glucagon and insulin merit further study in hepatorenal syndrome cases.

Energy, Water, and Solute Balance of the Ostrich Struthio camelus

The basal metabolic rate of adult ostrich (0.113 ml O2 g−1 h−1) is only 58% of the predicted value for a 100-kg nonpasserine bird. The basal metabolic rate of ratite birds appears to be best summarized as BMR (ml O2 h−1) = 389 kg0.73, which is parallel to and has about 60% of the intercept of the relationship for nonpasserine, carinate birds. The resting metabolic rate of ostrich (0.26 ml g−1 h−1; 2.3 × basal metabolism) was similar to the predicted basal rate. The maximal factorial metabolic scope of ostrich is at least 28 × basal. The daily energy turnover rate of ostrich with ad lib. water was 12,700 kJ day−1, which is equivalent to 0.26 ml O2 g−1 h−1. Daily energy intake dropped to 1,360 kJ day with water deprivation, but daily energy turnover remained high at about 15,000 kJ day−1. The digestive efficiency of ostrich with ad lib. water for lucerne was 43% of the ingested energy. Ostrich appear to digest a significant fraction of the cellulose in their diet. The daily water turnover rate of ostrich consuming dry lucerne with ad lib. water was 8.3 liters day−1. Drinking was the main source of water gain (7.9 liters day−1), and urine (2.5 liters day−1) and fecal water (2.9 liters day−1) were the main avenues for water loss. The cutaneous evaporation of adult ostriches (0.6 liters day−1) constituted 40% of the total evaporative water loss. Minimal respiratory water loss was 0.82 liters day−1 (1.3 mg/ml O2 consumed). Ostrich could not maintain body mass when water deprived. The rate of water intake for the ostrich without drinking water was 0.83 liters day−1; most of this was metabolic water. The rate of water loss was at least 2.21 liters day−1. Plasma sodium concentration increased, but potassium and osmotic concentrations were unchanged after 7 days of water deprivation. Birds with ad lib. water and water deprived had a similar urinary solute loss (osmotic clearance = 1.25 liters day−1). However, urine flow rate declined with water deprivation from 2.5 to 0.5 liters day−1, and urine osmotic concentration increased from 163 to as high as 800 mOsm kg−1 (U/P ratio of 2.5), to conserve water. Rapid rehydration by drinking of 12-14 liters of water (17% body mass) in 3 h diluted the body water pool as expected, but the decreases in ionic and osmotic concentrations of the plasma were less than expected. The moderate plasma dilution during rapid rehydration would be insufficient to cause hemolysis of red blood cells. The water economy of the ostrich is similar to that of other large savannah and desert animals, such as antelope and the camel, although the partitioning of water loss differs. The ostrich has a lower evaporative water loss and a higher fecal and urinary loss than mammals of similar mass.

Effects of the acute and chronic administration of indapamide on systemic and renal haemodynamics in essential hypertension.

The effects of acute and chronic administration of indapamide on systemic and renal haemodynamics were studied in 10 patients with arterial essential hypertension. No important changes were observed on mean arterial blood pressure, cardiac index and total peripheral resistance during acute administration of the drug. Chronic administration produced a significant reduction in both mean arterial blood pressure and total peripheral resistance whereas the cardiac index did not change. Glomerular filtration rate diminished significantly during the acute administration of the drug, while renal plasma flow remained unchanged. Urinary volume did not change whereas osmotic clearance increased and free water clearance decreased evidently. Both urinary sodium and potassium increased significantly during acute administration of indapamide. Long-term administration of this substance had no effect on renal haemodynamics.

Diuretic and antihypertensive activities of Traxanox sodium (TRX)

The diuretic and antihypertensive activities of TRX in mice and rats were compared with those of tienilic acid (TA) and trichlormethiazide (TCM). In saline loaded animals, TRX showed diuretic activity at oral doses from 5 to 100 mg/kg in a dose dependent manner. TRX was more potent than TA, but less potent than TCM. Both TRX and TA increased the urinary excretion of uric acid, but TCM did not. TRX also increased urinary PGE2excretion antagonized by indomethacin. In the clearance test using rats, TRX, like TA and TCM, increased osmotic clearance and decreased free water clearance. However, TRX, unlike TA and TCM, increased urinary Ca and P excretion, suggesting that it acts on both the proximal and distal tubule. In experimental hypertensive rats, TRX was found to have more potent antihypertensive activity in repeated dosing than in single dosing. In renal hypertensive rats given the drug orally for 4 consecutive weeks, TRX exhibited a sustained effect at a dose of 30 mg/kg/day. Furthermore, TRX significantly retarded the development of hypertension in young spontaneously hypertensive rats and in renal hypertensive rats from 1 and 2 weeks after repeated treatments of 10 and 30 mg/kg/day, respectively. From these results, TRX shows potential as a diuretic and antihypertensive agent, having uricosuric activity.

Renal function, aldosterone, and vasopressin excretion following repeated long-distance running.

Renal and endocrine responses were studied in 10 male runners during a 20-day 500-km race. Overnight urine and prerun blood samples were taken prior to running on days 1, 2, 5, 8, 14, 17, and 20. Day 13 followed 70 h of rest. Urine flow rate, osmotic clearance, tubular free water reabsorption, urinary vasopressin excretion rate, and body weight were not significantly changed. Creatinine clearance was constant except for an elevation on day 5. Plasma osmolality was elevated on days 2, 14, and 17. Plasma sodium was increased (P less than 0.05) on days 2 and 13 but reduced on day 20. The percentage of filtered sodium excreted was significantly reduced on all nights following running and elevated on recovery day 13. Urinary aldosterone excretion rate was significantly elevated 162, 117, and 97% on days 5, 8, and 20 and returned to control levels on day 13 after 70 h of rest. These data suggest that in response to repeated long-distance running normal fluid balance is regained within 12 h. However, it is necessary to conserve sodium for at least 24 h after exercise as evidenced by the decrease in the percent filtered sodium excreted and continued elevation of aldosterone excretion.

Urine concentration dynamics in the postprandial and the fasting Myotis lucifugus lucifugus

1. 1. The postprandial bat initially increased urine flow rate and urine concentration and 7–9.5 hr later decreased urine flow rate while maintaining an elevated urine concentration. 2. 2. The fasting bat produced an increasingly concentrated urine at a uniform rate. 3. 3. The relationship of osmotic clearance to urine flow rate in the postprandial bat suggests an increase in glomerular filtration rate (GFR) in the bat kidney in response to food intake and a decrease in GFR when wastes have been removed. 4. 4. Alterations in GFR with feeding may aid this periodically feeding insectivore to minimize urinary water loss.

Renal effects of bumetanide, a new saluretic agent.

The renal effects of bumetanide, a new diuretic chemically related to furosemide, have been studied in four young healthy volunteers during dehydration and water diuresis. Bumetanide produced a considerable diuresis due mainly to an increase in osmotic clearance. The peak urinary volume amounted to about 1/3 of the filtered volume, indicating an effect of the drug on the proximal tubule. Free water clearance was not significantly affected. During dehydration, with its superimposed osmotic diuresis, bumetanide diminished the concentrating power of the kidney so that an almost isotonic urine was produced. This result implied an additional effect on the distal parts of the nephron and it may represent partial blockade of sodium reabsorption in the ascending limb of the loop of Henle.

Water and Sodium Excretion after Blood Volume Expansion under Conditions of Constant Arterial, Venous and Plasma Oncotic Pressures and Constant Haematocrit

1. The diuretic and natriuretic responses occurring during expansion of blood volume by homologous blood transfusion were studied in homologous kidneys transplanted to the neck of hydropenic dogs that had previously been given deoxycorticosterone acetate and antidiuretic hormone. The experimental conditions ensured constant arterial perfusion pressure, venous pressure, osmotic pressure, haematocrit and plasma oncotic pressure. 2. Moderate but significant increases in urine output, renal sodium excretion, osmotic clearance and tubular sodium rejection fraction were observed; there were no significant changes in glomerular filtration rate, renal blood flow, postglomerular haematocrit and postglomerular plasma protein concentration 20 and 40 min after the end of blood infusion. 3. As the non-hormonal factors known to modulate sodium excretion underwent no significant change, the results are compatible with the proposition that a specific factor (‘natriuretic hormone’) plays a role in the mechanism of natriuresis after blood volume expansion.

The effect of furosemide on the function of normal and diseased kidneys in patients with unilateral pyelonephritis.

Abstract. In nine patients with unilateral pyelonephritis the renal function has been measured by the split function technique before and after the i.v. injection of furosemide. Before the injection the excretion fraction of sodium and chloride as well as the diuresis, the osmotic clearance and the free water clearance per unit of glomerular filtrate were greatest, and the urinary concentration of inulin was least, in the pyelonephritic kidneys. After the injection of furosemide these differences were no longer significant. When related to the osmotic clearance, the free water clearance was reduced in all kidneys after the injection. The findings are compatible with the presence of a functioning loop of Henle in most nephrons of the pyelonephritic kidneys.

Renal function in unilateral, parenchymatous renal disease in normotensive and hypertensive patients.

In 32 patients with unilateral, parenchymatous renal disorders (16 with hypertension), filtration fraction of affected and normal kidneys, and the ratio between filtration fractions of affected and normal kidneys, were greatest in hypertensive patients. The excretion fraction of sodium and the osmotic clearance per unit glomerular filtrate were greater and the urinary concentration of inulin was least in affected kidneys without difference between normotensive and hypertensive patients. It is suggested that hypertension affects diseased and normal kidneys in the same way.

Cardiorenal hemodynamic effects of ethacrynic acid

Ethacrynic acid, studied in normal subjects as well as in patients with hypertension or edema, reduces glomerular filtration rate slightly and has little or no effect on estimated renal plasma flow while decreasing filtration fraction. It causes a prompt increase in the volume of urine, with the excretion of 8 to 19 per cent of sodium filtered 30 minutes after intravenous administration. It also produces a reduction in urine pH, as well as a profuse diuresis of chloride and a lesser diuresis of potassium. With large doses there is a slight increase in the excretion of uric acid, whereas with lower doses there is retention of uric acid. In well-hydrated patients, the clearance of free water is reduced when osmotic clearance is maximal. The systemic hemodynamic effects of the drug are not striking. In our study, cardiac index and right atrial pressure fell after acute administration, whereas heart rate and total systemic resistance increased slightly. Although there was a tendency for blood pressure to fall in patients treated with ethacrynic acid in both the acute and subacute studies, the post-drug values were not significantly different from control values. The renal and systemic hemodynamic effects of the drug are best explained by a reduction in the plasma or circulating blood volume caused by the profuse diuresis of electrolytes and, to a lesser extent, water. The renal effects which we observed could be explained on the basis of a reduction in the reabsorption of sodium in the ascending loop of Henle or by an effect of ethacrynic acid on the proximal and distal tubular sodium reabsorption sites. Ethacrynic acid increased the osmolality of the urine in one patient with diabetes insipidus slightly more than did chlorothiazide in similar studies. Ethacrynic acid is a potent diuretic capable of causing massive loss of electrolytes and water. No adverse effects on hemopoietic, hepatic, or central-nervous-system function were noted in this short-term study.