Derivation of a new formula for calculating urinary electrolyte-free water clearance based on the Edelman equation

2005 ◽  
Vol 288 (1) ◽  
pp. F1-F7 ◽  
Author(s):  
Minhtri K. Nguyen ◽  
Ira Kurtz
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Empirical Relationship ◽  
Free Water ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Total Body ◽  
New Formula ◽  
The Relationship ◽  
Water Clearance

In evaluating the renal mechanisms responsible for the generation of the dysnatremias, an analysis of free water clearance (FWC) and electrolyte-free water clearance (EFWC) is often utilized to characterize the rate of urinary free water excretion in these disorders. Previous analyses of FWC and EFWC have failed to consider the relationship among plasma water Na+ concentration ([Na+]pw), total exchangeable Na+ (Nae), total exchangeable K+ (Ke), and total body water (TBW); (Edelman IS, Leibman J, O'Meara MP, and Birkenfeld LW. J Clin Invest 37: 1236–1256, 1958). In their derivations, the classic FWC and EFWC formulas fail to consider the quantitative and physiological significance of the slope and y-intercept in this equation. Consequently, previous EFWC formulas incorrectly assume that urine is isonatric when [Na+ + K+]urine = [Na+]p or [Na+ + K+]urine = [Na+]p + [K+]p (where [Na+]p and [K+]p represent plasma Na+ and K+ concentrations, respectively). Moreover, previous formulas cannot be utilized in the setting of hyperglycemia. In this article, we have derived a new formula termed modified electrolyte-free water clearance (MEFWC) for determining the electrolyte-free water clearance, taking into consideration the empirical relationship between the [Na+]pw and Nae, Ke, and TBW: MEFWC = V [1 − 1.03[Na+ + K+]urine/([Na+]p + 23.8)]. MEFWC, unlike previous formulas, is derived based on the requirement of the Edelman equation that urine is isonatric only when [Na+ + K+]urine = (Nae + Ke)/TBW = 0.97[Na+]p + 23.1. Furthermore, since we have shown that the y-intercept in the Edelman equation varies directly with the plasma glucose concentration, in patients with hyperglycemia, MEFWC = V [1 − 1.03[Na+ + K+]urine/{[Na+]p + 23.8 + (1.6/100)([glucose]p − 120)}]. The MEFWC formula will be especially useful in assessing the renal contribution to the generation of the dysnatremias.

Disorders of water and sodium homeostasis

2010 ◽  
pp. 3817-3831 ◽  
Author(s):  
Michael L. Moritz ◽  
Juan Carlos Ayus
Keyword(s):  
Water Intake ◽  
Free Water ◽  
Serum Osmolality ◽  
Urinary Volume ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Sodium Homeostasis ◽  
Plasma Electrolytes ◽  
Water Clearance

Water intake and the excretion of water are tightly regulated processes that are able to maintain a near-constant serum osmolality. Sodium disorders (dysnatraemias—hyponatraemia or hypernatraemia) are almost always due to an imbalance between water intake and water excretion. Understanding the aetiology of sodium disorders depends on understanding the concept of electrolyte-free water clearance—this is a conceptual amount of water that represents the volume that would need to be subtracted (if electrolyte-free water clearance is positive) or added (if negative) to the measured urinary volume to make the electrolytes contained within the urine have the same tonicity as the plasma electrolytes. It is the concentration of the electrolytes in the urine, not the osmolality of the urine, which ultimately determines the net excretion of water....

Free water excretion in normal dogs

1962 ◽  
Vol 202 (6) ◽  
pp. 1131-1135 ◽  
Author(s):  
E. Lovell Becker ◽  
H. Earl Ginn
Keyword(s):  
Sodium Chloride ◽  
Sodium Sulfate ◽  
Free Water ◽  
Maximal Rate ◽  
Water Diuresis ◽  
Osmotic Diuresis ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Early Increase ◽  
Water Clearance

Free water excretion (Chh2o = V - Cosm) was studied in unanesthetized dogs. This parameter of urine dilution was defined by superimposing an osmotic diuresis upon a water diuresis. Sodium sulfate (1.5%) gave the smallest free water clearance and sodium chloride (0.95%) the greatest, urea (1.65%) and mannitol (5.0%) being intermediary in their effects. Observed free water clearances were never maximal and, when plotted as Cosm vs. V, gave a slope of less than one. Two mercurial diuretics, meralluride and mercaptomerin, gave intermediary values for free water. Meralluride caused an early increase in free water clearance because of the theophylline incorporated in the compound. Later results were similar to those with mercaptomerin, both compounds producing free water clearances approaching a maximal rate.

Nonoxidative glucose metabolism a prerequisite for formation of dilute urine

1982 ◽  
Vol 242 (5) ◽  
pp. F491-F498
Author(s):  
A. D. Baines ◽  
B. D. Ross
Keyword(s):  
Glucose Metabolism ◽  
Free Water ◽  
Glucose Production ◽  
Inhibitory Effect ◽  
Sodium Reabsorption ◽  
Diluting Segment ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Total Sodium ◽  
Water Clearance

To examine links between norepinephrine- (NE) stimulated sodium transport and gluconeogenesis, we perfused isolated rat kidneys with 6% albumin, containing various combinations of glucose, alanine, pyruvate. and lactate and inhibitors of gluconeogenesis (0.1 mM mercaptopicolinate, MP) or glucose metabolism (0.2-0.5 mM 2-deoxyglucose, DG). Inulin clearance, fractional potassium reabsorption, total sodium reabsorption, and free water clearance were higher in kidneys perfused with 5 mM glucose plus 2 mM alanine than in kidneys perfused with either 10 mM lactate or 5 mM pyruvate. NE, added after 40 min of perfusion, decreased fractional sodium and potassium excretion in all experiments. In lactate- and/or pyruvate-perfused kidneys NE decreased fractional water excretion with little increase in free water clearance; free water formation was lowest in kidneys perfused with DG or MP. Glucose (5 mM) reversed the inhibitory effect of MP on free water clearance. In glucose-perfused kidneys NE did not decrease fractional water excretion, whereas free water clearance increased threefold. NE stimulated glucose production from pyruvate 2.4-fold and from lactate 1.6-fold. MP inhibited gluconeogenesis both in the basal state and after NE. We conclude that the formation of dilute urine requires nonoxidative glucose metabolism to maintain low water permeability in the diluting segment and a high peritubular glucose concentration that is ensured by gluconeogenesis in adjacent proximal tubules.

Effect of V1/V2-receptor antagonism on renal function and response to vasopressin in conscious dogs

1991 ◽  
Vol 260 (2) ◽  
pp. F273-F282
Author(s):  
C. E. Rose ◽  
K. Y. Rose ◽  
L. B. Kinter
Keyword(s):  
Renal Function ◽  
Receptor Antagonist ◽  
Free Water ◽  
Simultaneous Administration ◽  
Free Water Clearance ◽  
Water Excretion ◽  
V2 Receptor ◽  
Arterial Plasma ◽  
V2 Receptor Antagonist ◽  
Water Clearance

To characterize effects of V1- and V2-receptor stimulation on renal function, eight conscious mongrel female dogs were studied in four separate studies greater than or equal to 2 wk apart during the following six consecutive 20-min periods: 1) intrarenal administration of the full V1/V2-receptor antagonist SKF 105494 (100 ng.kg-1.min-1) during basal circulating vasopressin (VP) levels (n = 3), 2) elevation of renal arterial plasma VP concentrations by intrarenal administration of exogenous arginine VP (0.05 mU.kg-1.min-1, n = 5), 3) simultaneous administration of SKF 105494 at (100 ng.kg-1.min-1) with intrarenal administration of exogenous VP (0.05 mU.kg-1.min-1; n = 5), and 4) intrarenal vehicle alone (n = 5). When administered during conditions of basal circulating endogenous VP, the full receptor antagonist effects were limited to opposition of hydrosmotic effects of VP. Elevation of renal arterial plasma VP levels through infusion of exogenous VP resulted in decreased renal plasma flow, glomerular filtration rate, osmolar clearance, urinary flow rate, and free water clearance and increased urine osmolality. These effects were all abolished by simultaneous administration of V1/V2-receptor antagonist. These data suggest that, under basal low levels of circulating VP, VP only influences renal water excretion. However, when plasma VP concentrations are elevated, VP may contribute to renal vasoconstriction and secondarily to reduced solute excretion, in addition to its effects on free water clearance.

Disorders of water and sodium homeostasis

2020 ◽  
pp. 4729-4747
Author(s):  
Michael L. Moritz ◽  
Juan Carlos Ayus
Keyword(s):  
Water Intake ◽  
Serum Sodium ◽  
Free Water ◽  
Sodium Concentration ◽  
Serum Sodium Concentration ◽  
Water Losses ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Electrolyte Disorder ◽  
Water Clearance

Water intake and the excretion of water are tightly regulated processes that are able to maintain a near-constant serum osmolality. Sodium disorders (dysnatraemias—hyponatraemia or hypernatraemia) are almost always due to an imbalance between water intake and water excretion. Understanding the aetiology of sodium disorders depends on understanding the concept of electrolyte-free water clearance—this is a conceptual amount of water that represents the volume that would need to be subtracted (if electrolyte-free water clearance is positive) or added (if negative) to the measured urinary volume to make the electrolytes contained within the urine have the same tonicity as the plasma electrolytes. It is the concentration of the electrolytes in the urine, not the osmolality of the urine, which ultimately determines the net excretion of water. Hyponatraemia (serum sodium concentration <135 mmol/litre) is a common electrolyte disorder. It is almost invariably due to impaired water excretion, often in states where antidiuretic hormone release is (1) a normal response to a physiological stimulus such as pain, nausea, volume depletion, postoperative state, or congestive heart failure; or (2) a pathophysiological response as occurs with thiazide diuretics, other types of medications, or in the syndrome of inappropriate diuresis; with both often exacerbated in hospital by (3) inappropriate iatrogenic administration of hypotonic fluids. Hypernatraemia (serum sodium concentration >145 mmol/litre) is a common electrolyte disorder that occurs when water intake is inadequate to keep up with water losses. Since the thirst mechanism is such a powerful stimulus, hypernatraemia almost invariably occurs in the context of an illness and care that restricts the patient’s access to water. This chapter discusses the clinical features, management, and prevention of hyponatraemia and hypernatraemia.

Osmotic thresholds for AVP release with the use of plasma and urine AVP and free water clearance

1989 ◽  
Vol 256 (4) ◽  
pp. R892-R897 ◽  
Author(s):  
A. M. Moses
Keyword(s):  
Plasma Osmolality ◽  
Free Water ◽  
Normal Subjects ◽  
Free Water Clearance ◽  
Linear Relationships ◽  
Osmotic Stimulation ◽  
Glomerular Filtrate ◽  
The Mean ◽  
The Relationship ◽  
Water Clearance

Eleven hydrated normal subjects were infused with hypertonic saline so that plasma osmolalities (POsmol) ranged from 280 to 306 mosmol/kg. Linear relationships were calculated between POsmol and plasma and urine arginine vasopressin (AVP) in the 11 individual subjects. There was an excellent linear correlation between POsmol and plasma and urine AVP, with the latter as concentration or rate of excretion. The highest correlation coefficient occurred when urine AVP was expressed as microunits of AVP per 100 milliliters of glomerular filtrate. The smallest coefficient of variation of the slopes occurred when urine AVP was expressed as microunits of AVP per minute. The osmotic thresholds obtained by abscissal intercepts from relating POsmol to urine AVP per minute or per 100 milliliters of glomerular filtrate were 285.9 and 285.5 mosmol/kg, respectively. These values did not differ from the mean osmotic threshold obtained by traditional free water clearance changes (285.8 mosmol/kg). Analysis of the relationship between plasma osmolality and plasma AVP resulted in the greatest variation in slope and osmotic threshold, with the latter being significantly lower than that obtained by free water clearance changes. The data also demonstrated a much more rapid rise of urine than of plasma AVP under the stated conditions of osmotic stimulation.

Effect of forward acceleration on renal function

1962 ◽  
Vol 17 (3) ◽  
pp. 413-416 ◽  
Author(s):  
John F. Watson ◽  
Rita M. Rapp
Keyword(s):  
Negative Pressure ◽  
Human Subjects ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Free Water ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Normal Human ◽  
Negative Pressure Breathing ◽  
Water Clearance

The effect of forward acceleration on renal hemodynamics, electrolyte excretion, and water clearance has been studied in six normal human subjects. Forward acceleration produced a slight increase in glomerular filtration rate and effective renal plasma flow during and after stress. After centrifugation there was a 20–35-min lag before the appearance of an increase in urine volume and free water clearance. These changes in water excretion were transient and were not accompanied by a natriuresis nor associated with changes in serum osmolality. Physiologic responses to forward acceleration and negative pressure breathing were compared. It was suggested that forward acceleration, like negative pressure breathing, may induce an increase in intrathoracic blood volume which inhibits the release of antidiuretic hormone via a nonosmotic volume-sensitive receptor mechanism located within the intrathoracic vascular space. Submitted on September 14, 1961

Glycerol hyperhydration: hormonal, renal, and vascular fluid responses

1995 ◽  
Vol 79 (6) ◽  
pp. 2069-2077 ◽  
Author(s):  
B. J. Freund ◽  
S. J. Montain ◽  
A. J. Young ◽  
M. N. Sawka ◽  
J. P. DeLuca ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Free Water ◽  
Fluid Retention ◽  
Urine Flow ◽  
Plasma Aldosterone ◽  
Water Reabsorption ◽  
Free Water Clearance ◽  
Flow Rates ◽  
Total Body ◽  
Water Clearance

Glycerol ingestion has been shown to mediate hyperhydration; however, the mechanism(s) responsible for this improved fluid retention is not well understood. This study examined the hormonal, renal, and vascular fluid responses to glycerol hyperhydration in 11 resting male volunteers who ingested one of two experimental solutions and then a water bolus. The volume of fluid ingested was determined from the subjects' measured total body water (TBW; total volume = 37 ml/l TBW, 1,765 +/- 162 ml). Experimental solutions (5.0 ml/l TBW) were matched for color and taste and differed only in that one contained 1.5 g glycerol/l TBW (total osmolar load = 777 +/- 24 mosmol). Nine of the 11 subjects also completed a control trial during which no fluid was ingested. Glycerol ingestion (GI) resulted in greater fluid retention than the ingestion of water alone (WI; 60 vs. 32% 3-h posthyperhydration, P < 0.01). This improved fluid retention with GI resulted from lower urine flow rates (peak 6.2 vs. 10.5 ml/min, P < 0.01) associated with lower free water clearance rates (peak = 1.2 vs. 8.2 ml/min, P < 0.01). Hyperhydration had no effect on plasma atrial natriuretic peptide concentrations. Changes in plasma aldosterone were unrelated to differences in fluid retention. Antidiuretic hormone concentrations (ADH) were significantly reduced from prehyperhydration levels during both hyperhydration trials but tended (P = 0.07) to rise during GI compared with WI at the very time urine flow and free water clearance differences were also evident. This suggests that ADH may, in part, be responsible for glycerol's effectiveness, although differences in ADH concentrations were small and near the assay's sensitivity limits. Alternatively, glycerol's effectiveness may result from its directly increasing the kidneys' medullary concentration gradient and, hence, water reabsorption.

Salt depletion inhibits cerebral-induced natriuresis in the dog

1984 ◽  
Vol 247 (5) ◽  
pp. F725-F728 ◽  
Author(s):  
J. P. Gilmore ◽  
M. N. Nemeh
Keyword(s):  
Sodium Excretion ◽  
Free Water ◽  
Free Water Clearance ◽  
Conscious Dog ◽  
Sensing Mechanism ◽  
Body Sodium ◽  
Salt Depletion ◽  
Total Body ◽  
Renal Responses ◽  
Water Clearance

Experiments were carried out in the conscious dog to determine whether renal responses to intracarotid (IC) infusion of hypertonic NaCl are altered in the sodium-depleted state. In the sodium-replete animal, both IC and IV infusion of hypertonic NaCl produced significant increases in sodium excretion and significant decreases in free water clearance. However, both of these renal responses were more rapid in onset with IC infusion. Both IC and IV infusion decreased free water clearance. In the sodium-deplete animal, IC hypertonic NaCl infusion had no effect on sodium excretion but did decrease free water clearance. It is concluded that total body sodium is a determinant of the gain of the cerebral sodium-sensing mechanism and that this mechanism is different from the osmosensitive mechanism.

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