Increased Solute Excretion Research Articles

Polyuria: A Pathophysiologic Approach

Polyuria: A Pathophysiologic Approach

Interactions between angiotensin II and arginine vasopressin in water homeostasis

Mice deficient in the angiotensin II type 1a (AT(1a)) receptor demonstrate a vasopressin-resistant nephrogenic diabetes insipidus. These knockout mice exhibit a threefold increase in 24-h urine excretion. Neither 2 weeks of exogenous vasopressin nor 5 days of fluid restriction reversed this polyuric state. This nephrogenic diabetes insipidus was associated with reductions in adenylyl cyclase protein and in the phosphorylated mitogen-activated protein kinase extracellular signal-regulated kinase 1/2. The results support an important interaction between vasopressin and angiotensin II in maximal urinary concentration.

Polyuria of thyrotoxicosis: Downregulation of aquaporin water channels and increased solute excretion

Thyrotoxicosis is a common disorder causing cardiovascular and renal irregularities. In this study, thyrotoxicosis was produced in rats by 14 days of daily thyroxine injection. This was associated with an increase in cardiac index, mean arterial pressure, and renal blood flow compared with euthyroid controls. Food and water intake along with urine output were significantly increased in the thyrotoxic rats compared with control animals associated with a significant increase in solute excretion. Polyuria and increased solute excretion still occurred even when food and water intake was equivalent. These renal responses were associated with significant decreases in AQP1 and AQP2 water channel expression in both the ad lib and paired intake studies in the cortex and inner medulla. The downregulation of AQP2 protein occurred in spite of equivalent plasma arginine vasopressin (AVP) in the ad lib and increased AVP in the paired feeding studies. Solute-free water reabsorption was greater in both the ad lib and paired thyrotoxic than euthyroid rats and was associated with increased Na-K-2Cl cotransporter expression. We propose that the AVP-independent downregulation of AQP2, the observed increase in renal arterial pressure, and decrease in filtration fraction contribute to polyuria the increased solute excretion in spite of enhanced ion transporters in thyrotoxicosis.

Desmopressin Resistant Nocturnal Polyuria Secondary to Increased Nocturnal Osmotic Excretion

We investigated the role of increased solute excretion in children with desmopressin resistant nocturnal enuresis and nocturnal polyuria. A total of 42 children with monosymptomatic nocturnal enuresis and significant nocturnal polyuria with high nocturnal urinary osmolality (more than 850 mmol/l) were not responding to desmopressin. A 24-hour urinary concentration profile was obtained with measurement of urine volume, osmolality, osmotic excretion and creatinine. The control group consisted of 100 children without enuresis. Based on osmotic excretion patients were classified into 3 groups. Group 1 had 24-hour increased osmotic excretion, most likely secondary to a high renal osmotic load. This was probably diet related since 11 of these 12 patients were obese. Group 2 had increased osmotic excretion in the evening and night, probably due to a high renal osmotic load caused by the diet characteristics of the evening meal. Group 3 had deficient osmotic excretion during the day, secondary to extremely low fluid intake to compensate for small bladder capacity. Nocturnal polyuria with high urinary osmolality in our patients with desmopressin resistant monosymptomatic nocturnal enuresis is related to abnormal increased osmotic excretion. This may be explained by their fluid and diet habits, eg daytime fluid restriction, and high protein and salt intake.

Intravenous Dopamine Associated with Nephrogenic Diabetes Insipidus-Like Syndrome

Dopamine is often used for maintenance of haemodynamic stability in critically ill patients in the setting of intensive care units. ‘Renal’ doses (1 to 2 μg/kg/min) or ‘pressor’ doses (above 5 to 10 μg/kg/min) are used distinctly for various clinical disorders. Dopamine may be associated with diabetes insipidus, manifested by serum hypertonicity, urine hypotonicity and polyuria.[1] The mechanism of the potentiation of free water excretion remains obscure, although inhibition of pituitary vasopressin or increased solute excretion have been proposed.[1] In this case report, we describe a patient who developed acute diabetes insipidus associated with dopamine administration, where neither of these mechanisms appears likely.

Endogenous ANP augments fractional excretion of Pi, Ca, and Na in rats with reduced renal mass.

Atrial natriuretic peptide (ANP) infusion increases fractional excretion of many solutes including sodium, chloride, bicarbonate, phosphate, calcium, and magnesium. Because fractional excretion of these solutes increases with advancing renal disease, and because plasma ANP levels are known to be elevated in chronic renal failure, we sought to determine whether ANP mediates increased solute excretion rates per nephron in rats following extensive renal ablation, a model of chronic renal failure. Because sodium restriction decreases plasma ANP levels in the setting of reduced renal mass, we also determined the effect of sodium restriction on sodium, phosphate, calcium, and magnesium excretion rates in rats with 5/6 nephrectomy (NX). We also assessed whether high endogenous ANP levels influence fractional sodium, phosphate, calcium, and magnesium excretion in rats with 5/6 NX, by inhibiting ANP action via infusion of a high-affinity ANP antiserum. Whole-kidney glomerular filtration rate in 5/6 NX rats averaged approximately one-third that of shams, and plasma ANP levels were significantly elevated in these rats above those of shams, but to a lesser extent in rats on low- vs. high-salt intakes. Fractional sodium, phosphate, and calcium, but not magnesium excretion rates were significantly greater in 5/6 NX rats on the higher sodium intake compared with those in 5/6 NX rats on the lower sodium intake. Moreover, in 5/6 NX rats on the higher sodium intake, ANP antiserum significantly reduced fractional sodium, phosphate, and calcium excretion, but was without effect on magnesium excretion. These data implicate endogenous ANP in promoting the adaptive increase in sodium, phosphate, calcium, but not magnesium excretion per nephron in chronic renal disease.

Arginine vasopressin, circulation, and kidney during graded water immersion in humans.

Ten normal males rested sitting upright at an air temperature of 28 degrees C for 5.5 h (control, C) and underwent 4 h of graded water immersion (WI) to the umbilicus (UI), to the chest (CI), and to the neck (NI), respectively (water temperature = 34.5 degrees C), on different experimental days. Plasma arginine vasopressin (PAVP) was suppressed during WI compared with C and maximally so during NI. However, there was no change in PAVP comparing CI with UI even though central venous pressure (CVP) increased. CVP increased during CI and NI compared with C but was unchanged during UI, whereas cardiac output (rebreathing method), stroke volume, and plasma volume increased to approximately the same level during all three steps of WI compared with C. Heart rate and total peripheral vascular resistance decreased during UI, CI, and NI. Systolic arterial pressure (SAP) and pulse pressure (PP) were increased gradually from prestudy related to the degree of WI. Also diuresis, natriuresis, kaliuresis, osmotic excretion, and clearance were increased gradually compared with C, whereas free water clearance (CH2O) gradually decreased. There were weak negative but statistically significant correlations between PAVP and CVP and between changes in PAVP from prestudy and corresponding changes in SAP and PP. Furthermore, a statistically significant and negative correlation between CH2O and natriuresis could be established. We conclude that graded immersion gradually increases central blood volume and decreases PAVP. However, not only cardiopulmonary mechanoreceptors but also arterial baroreceptors may play a role in AVP suppression during WI in humans. In hydropenic subjects the suppression of PAVP during WI is apparently not effective in counteracting the decrease in CH2O induced by increased solute excretion.

Kidney Function of Single Comb White Leghorn Pullets Following Acute Renal Portal Infusion of the Mycotoxin Citrinin

Poultry consuming diets contaminated with citrinin excrete copious quantities of urine and exhibit increased water consumption. The present study was conducted to determine if citrinin acts directly on the kidneys and, if so, to provide a detailed physiological evaluation of the nephrotoxic effects of citrinin. Single Comb White Leghorn pullets were anesthetized and prepared for renal function studies. Ureteral urine was collected during a pre-infusion period (30 min), during unilateral renal portal infusion of 200 ppm citrinin (30 min), and during a recovery period following citrinin infusion (90 min). Pilot studies had shown that 200 ppm citrinin is the lowest dose capable of causing consistent unilateral responses when infused at a rate of .2 ml/kg body weight (BW)·min. The responses of the portal-infused kidneys were compared with the responses of the contralateral (uninfused) kidneys to determine the direct effects of citrinin.Citrinin had no acute direct (unilateral) effect on glomerular filtration rate, renal plasma flow rate, urine pH, or fractional calcium or magnesium excretion. Citrinin caused rapid unilateral increases in urine flow rates, free water clearance, and in fractional sodium, potassium, and inorganic phosphate excretion. Increased solute excretion did not compensate for increased free water clearance, as reflected by a significant decrease in urine osmolality. Recovery from the effects of citrinin occurred within 30 min after cessation of unilateral renal portal infusion. No histopathological damage was seen when citrinin was infused at 200 and 800 ppm, although dose-related increases in urine flow and decreases in urine osmolality were observed. These results indicate that citrinin acts directly on the kidneys to alter several tubular transport processes, and that the effects of citrinin are reversible.

Sucrose or Glucose for Diarrhea

Water moves along osmotic gradients. Acute diarrhea is due to impaired solute absorption or to increased solute excretion. It seems reasonable, as well as traditional, to lower the osmolarity of the gut's contents in diarrhea by starvation and water. Breast milk, when fully digested, has nearly twice the osmolarity of plasma, and giving it (or bread and butter1) as advocated in Dacca2 might prolong diarrhea. The 24-hour purging rate of the patients of Black et al on an unknown quantity of milk equalled that of the first eight hours, and diarrhea persisted for 60 hours.

Cellular calcium uptake in the action of prostaglandins on renal water excretion

The role of cellular calcium uptake in the antidiuretic response to vasopressin was studied in anesthetized dogs undergoing water diuresis. In prostaglandin (PG) intact animals, an intrarenal infusion of verapamil caused only a modest blunting of the response to antidiuretic hormone (ADH), because the urinary osmolality (UOsm) achieved in the contralateral control kidney was 338 +/- 40 mOsm/kg H2O but was only 270 +/- 23 mOsm/kg H2O in the verapamil-infused kidney. The possibility was then studied that PG inhibit the action of ADH by impairing cellular calcium uptake. If so, verapamil would be expected to abolish the effect of PG inhibition to enhance the action of ADH. In eight PG-inhibited dogs, the control kidney's UOsm increased to a mean of 650 +/- 103 mOsm/kg H2O but only to 280 +/- 22 mOsm/kg H2O in the infused side. Thus, verapamil abolished the effect of PG inhibition to enhance the action of ADH. Likewise in five dogs a second chemically dissimilar inhibitor of calcium transport, proadifen, also abolished the effect of PG inhibitors as UOsm rose to 590 +/- 78 mOsm/kg H2O in the control kidney but only to 278 +/- 11 mOsm/kg H2O in the proadifen-infused kidney. Neither prior vasodilatation nor an increased solute excretion with mannitol of a degree observed with verapamil mimicked the effect of the calcium uptake blockers to inhibit the action of ADH. The present in vivo studies therefore demonstrate that the effect of PG inhibitors to enhance the hydroosmotic effect of vasopressin involve cellular calcium transport.

Effect of norepinephrine on plasma vasopressin concentration and renal water metabolism.

In the anesthetized, normally hydrated dog, the i. v. infusion of norepinephrine (NE; 0.5 microgram/kg/min) resulted in an increased blood pressure and a marked reduction in the plasma vasopressin (ADH) concentration (2.6 +/- 0.2 to 1.1 +/- 0.2 muU/ml). Urine flow and osmolar clearance, and urine osmolality fell. However, the negative free water clearance (TcH2O) increased, despite the reduction in plasma ADH levels. Thus, the NE-induced diuresis appeared to be due largely to the increased solute excretion, but the reduction in plasma ADH levels may also have been a factor. These data show that change in free water clearance is not a satisfactory index of change in the plasma ADH levels may also have been a factor. These data show that change in free water clearance is not a satisfactory index of change in the plasma ADH concentration when there are acute changes in renal hemodynamics and solute excretion. The norepinephrine-induced reduction in ADH secretion appeared to be due largely to increased activity of the arterial baroreceptors, but a central action cannot be ruled out.

Mechanism of dopamine-induced diuresis in the dog.

This study was undertaken to evaluate the effect of dopamine (D) on renal water excretion. Intravenous (i.v.) infusion of D (7.5 microgram/kg per min) was associated with a significant, reversible increase in free water excretion (CH2O) and a decrease in urinary osmolality (Uosmol). These changes, however, were associated with significant increases in renal blood flow (RBF), glomerular filtration rate (GFR), and urinary sodium excretion (UNaV). These increases could have been responsible for the diuretic response to D. To examine whether D has a direct effect on vasopressin (ADH) release, D was infused into one common carotid artery at a dose equal to one-fourth the i.v. dose. No effects on CH2O and Uosmol were observed. To examine whether D might have an antagonistic effect on ADH a single bolus of ADH (100 mU) was given to the same hypophysectomized dogs with and without D infusion. The antidiuretic response to ADH was the same, whether or not D was given concomitantly. The net changes in Uosmol and CH2O in response to ADH were not significantly different. Taken together, the present results provide no evidence for a direct effect of D on ADH release nor do they indicate an interference with the peripheral action of ADH. The dopamine-induced diuresis is probably the result of increased solute excretion. This, in turn, is the result of the combined effects of dopamine on increasing renal blood flow, GFR, and sodium excretion.

POSTNATAL RENAL MATURATION IN LOW BIRTH WEIGHT INFANTS

The postnatal contraction of extracellular fluid in low birth weight (LBW) infants is associated with increased solute excretion. Patterns of postnatal renal maturation were assessed with the assumption that changes in body composition are mediated in part by the developing kidney. Twenty-two appropriate for gestational age, LBW infants, (birth weight m = 1380 gms, gestational ages m=31 wks) ware studied between 12 noun and 61 days to evaluate simultaneously glomerular and tubular functional maturation. Since most LBW infants have respiratory morbidities (respiratory distress followed by chronic lung disease) the infants were grouped into: Group I, (13 infants) transient or absent respiratory morbidities and Group II, (9 infants) persistent and severe respiratory morbidities. Creatinine clearance correlated directly with postnatal age in both groups, (Group I r=0.868 p<0.001 and Group II r=0.646 p<0.01) Sodium intake did not vary significantly with age in either group. Percent fractional sodium excretion was inversely related to postnatal age, (Group I r=-0.613 p<0.01 and Group II r=-0.646 p<0.01) and no significant difference was observed between the two regression lines. Increased % fractional sodium excretion in the first 10 days of life may reflect extracellular solute losses and persistent respiratory morbidities did not alter this homeostatic regulation.

STUDIES OF THE EFFECT OF LARGE DOSES OF BACTERIAL PYROGEN IN THE DOG: 2. AN EXPLANATION FOR THE URINE DILUTION

Previous studies with large IV doses of bacterial endotoxin in dogs have shown this material to cause a diuresis which is uniformly associated with a rise in total renal blood flow, increased solute excretion, and a fall in Uosm unresponsive to ADH. The present study has demonstrated that renal cortical tissue sodium concentration is unaffected by endotoxin whereas renal sodium concentration of outer and inner medullary portions showed a striking fall. Endotoxin-treated kidneys were compared to their respective paired control (no endotoxin). It is postulated that the rise in total renal blood flow, following endotoxin, is mainly medullary and causes a washout of medullary interstitium multiplier deposited sodium. The efficiency of the renal counter current exchanger is impaired and tubule to interstitium gradient reduced. This would account for observed falls in Uosm and relative unresponsiveness to ADH after endotoxin.

STUDIES OF THE EFFECT OF LARGE DOSES OF BACTERIAL PYROGEN IN THE DOG: 2. AN EXPLANATION FOR THE URINE DILUTION

Previous studies with large IV doses of bacterial endotoxin in dogs have shown this material to cause a diuresis which is uniformly associated with a rise in total renal blood flow, increased solute excretion, and a fall in Uosm unresponsive to ADH. The present study has demonstrated that renal cortical tissue sodium concentration is unaffected by endotoxin whereas renal sodium concentration of outer and inner medullary portions showed a striking fall. Endotoxin-treated kidneys were compared to their respective paired control (no endotoxin). It is postulated that the rise in total renal blood flow, following endotoxin, is mainly medullary and causes a washout of medullary interstitium multiplier deposited sodium. The efficiency of the renal counter current exchanger is impaired and tubule to interstitium gradient reduced. This would account for observed falls in Uosm and relative unresponsiveness to ADH after endotoxin.

Changes in urine concentration during prolonged administration of vasopressin and water.

Vasopressin and water were administered to dogs for periods of up to a month. The initial increase in urine osmolality was maintained for only 3–12 days. Thereafter, urine concentration fell to less than half the maximum value and remained at these lower levels indefinitely. The decrease was associated with expansion and dilution of body fluids. It could not be correlated with the rises in filtration rate which occur, nor with the decreased plasma osmolality and sodium per se, nor was it associated with increased solute excretion. A low salt diet alone or with desoxycosterone acetate (DCA) decreased the maximum urine concentration achieved after vasopressin. Adrenalectomy abolished this effect of the low salt diet.