Effective water clearance and tonicity balance:
the excretion of water revisited

Clin Invest Med 1997; 20(1): 16-24.

[résumé]

Reprint requests to: Dr. Jean Pierre Mallie, Laboratoire d'explorations fonctionnelles rénales, Centre Hospitalier Universitaire de Nancy, 54511 Vandoeuvre Cedex, France; fax 33 3 8315-4543

• Résumé
• Introduction
• Methods
• Results
• Discussion
• References

Abstract

Design: Prospective study.

Participants: Four normal subjects with no conditions affecting excretion, 10 patients with advanced congestive heart failure (CHF) and 5 patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Intervention: Normals and patients were administered a standard water load (20 mL per kg of body weight) during 45 minutes, and blood and urine samples were taken before, during and after the load was given.

Main outcome measures: Urine and blood sodium and potassium concentrations, osmolar clearance, free-water clearance, electrolyte clearance and EWC.

Results: The water load was excreted rapidly by normals, more slowly by patients with CHF, and not at all by patients with SIADH. The EWC was positive in normals and those with CHF, but negative in those with SIADH. In patients with CHF, the EWC, but not the free-water clearance, helped explain why hyponatremia was corrected after the water load was given.

Conclusions: In subjects with abnormal water excretion, the EWC provides the physiologic explanation for the renal role in variations in natremia. The authors propose a bedside evaluation of renal water and electrolyte handling that takes into consideration the role of urinary potassium in body tonicity. Changes in body tonicity can be explained by a "tonicity balance," a calculation in which the source and the net balance of sodium, potassium and water are considered.

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Résumé

Conception : Étude prospective.

Participants : Quatre sujets normaux sans problème d'excrétion, 10 patients atteints d'insuffisance cardiaque globale avancée et 5 patients atteints du syndrome d'antidiurèse inappropriée.

Intervention : On a administré aux patients une charge hydrique normale (20 mL par kg de masse corporelle) pendant 45 minutes et prélevé des spécimens de sang et d'urine avant, pendant et après l'administration de la charge.

Principales mesures des résultats : Concentrations de sodium et de potassium dans l'urine et le sang, clairance osmolaire, clairance de l'eau libre, clairance des électrolytes et clairance effective de l'eau.

Résultats : La charge hydrique a été excrétée rapidement par les sujets normaux, plus lentement par les patients atteints d'insuffisance cardiaque globale et pas du tout par les patients atteints du syndrome d'antidiurèse inappropriée. La clairance effective de l'eau a été positive chez les sujets normaux et ceux qui étaient atteints d'insuffisance cardiaque globale, mais négative chez ceux qui avaient le syndrome d'antidiurèse inappropriée. Chez les patients atteints d'insuffisance cardiaque globale, la clairance effective de l'eau, mais non la clairance de l'eau libre, a aidé à expliquer pourquoi l'hyponatrémie a été corrigée après l'administration de la charge hydrique.

Conclusions : Chez les sujets qui excrètent l'eau anormalement, la clairance effective de l'eau fournit l'explication physiologique du rôle des reins dans les fluctuations de la natrémie. Les auteurs proposent une évaluation au chevet de l'élimination de l'eau et des électrolytes par les reins, qui tient compte du rôle du potassium urinaire dans la tonicité du corps. Il est possible d'expliquer les changements de la tonicité du corps par un «équilibre de la tonicité», calcul qui tient compte de la source et de l'équilibre net du sodium, du potassium et de l'eau.

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Introduction

When one calculates an osmolar clearance, one does not adjust for the fact that some osmoles behave in a different fashion with regard to water distribution across cell membranes. It is now widely accepted that, although urea contributes to total body osmolality, it does not influence water movement at the interface between extracellular fluid (ECF) and intracellular fluid (ICF). As a result, the clinical practice is to use double the plasma sodium concentration as the "effective osmolality" or tonicity of body fluid compartments. Building on these accepted concepts, one should evaluate whether the urine excreted led to a rise or fall in the ICF volume. To achieve this aim, the urine should be examined in terms of tonicity rather than osmolality.[15­17]

We conducted this study to determine whether an osmolar clearance analysis was adequate to measure expected changes in body tonicity in patients with congestive heart failure (CHF) or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We also investigated whether the free-water clearance or the electrolyte-free water excretion reflects the renal response to changes in plasma tonicity resulting from a water load.

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Material and methods

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Results

Variations in urinary volume and its different components (osmolar clearance, free-water clearance; electrolyte clearance, effective water clearance) are shown in Fig 2. The free-water clearance was negative in the 3 groups before the water-load study; it increased rapidly in normal subjects, slightly in patients with CHF and remained negative in patients with SIADH.

Although the maximal values of the free-water clearance and the EWC were close in normal subjects, large differences between these measures were observed in patients with CHF and SIADH. In those with CHF, there was only a small positive free-water clearance, yet the EWC represented most of the urinary volume and was significantly positive (Fig. 2). In contrast, in patients with SIADH, both the free-water clearance and the EWC were negative throughout the study (Fig. 2).

Cumulative results for diuresis, free-water clearance and EWC are presented in Fig 3. The normal subjects excreted 100% of the water load within the first 3 hours (not shown in Fig. 3). The cumulative water excretion was considerably lower (less than 40%) in the patients with CHF and SIADH for the 4 hours of observation.

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Discussion

As expected, the plasma sodium concentration fell in all subjects who received the water load. For the first hour, both in the normals and the patients with CHF, the EWC was positive, whereas the free-water clearance was negative. Thus, the electrolyte-free water was excreted promptly after the water load, and this excretion limited the decline in the plasma sodium level. Subsequently, the plasma sodium level rose rapidly in controls and more slowly in patients with CHF, whereas it did not rise in patients with SIADH. This difference between patients with CHF and those with SIADH could not be explained by differences in urinary volume or free-water excretion because the free-water clearance was nil among those with CHF and negative among those with SIADH (Fig. 3). The basis for these changes in natremia were revealed by the EWC, which was always positive in the patients with CHF (whose plasma sodium level returned to baseline), but always negative in the patients with SIADH (whose plasma sodium level remained low). The normals and the patients with CHF both had a positive EWC, which constituted a large part (close to 80%) of their diuresis, so that their hyponatremia was spontaneously corrected. In the patients with CHF, the urine flow rate, and therefore the EWC, was smaller in absolute terms, so correction of the induced hyponatremia took longer than in the control subjects.

The negative EWC in the patients with SIADH was associated with a slightly increased electrolyte clearance. These patients did not excrete electrolyte-free water; therefore, the increase in ECF volume due to the water load was corrected by an increase in isotonic or hypertonic sodium chloride excretion, whereas the dilution induced by the water intake remained. Notwithstanding, their plasma sodium concentration could have risen later if the patients had consumed enough sodium chloride with a higher tonicity than that found in the urine (revealed by a tonicity balance).

In the remainder of the discussion, we will focus on 2 aspects of the interpretation of the tonicity balance. Several facts must be defined at the outset. First, the osmolality of the ICF and ECF are equal. Second, particles that achieve an equal concentration in the ICF and ECF (e.g., urea) should be ignored because they do not contribute to changes in water distribution. Since plasma glucose levels did not vary appreciably in these experiments, they will not be discussed, for simplicity's sake. (See Halperin and associates[25] for a more comprehensive discussion.) Accordingly, we will focus on the concentration of ions. Third, tonicity in body fluids is represented by the sum of the concentrations of all ions in interstitial fluid or 294 milliosmoles per kilogram of water; this value is close to twice the sum of sodium and potassium concentrations, rather than twice the sodium concentration, as employed previously.[10,21,22,26]

There are several points concerning potassium that require a more detailed consideration. As stated earlier, a clearance term should have the same factors in its numerator and denominator. Oversimplifying the electrolyte and electrolyte free-water clearances by not considering the plasma potassium concentration leads to a small quantitative error because the plasma potassium level is so much smaller than the sodium level. Of greater importance is an evaluation of potassium in the urine. One must consider whether the excretion of potassium represents the loss of one or two particles and whether this particle loss was from the ICF or the ECF or both. It is widely held that the excretion of potassium has an impact on body tonicity akin to that of sodium excretion.[27] Edelman and associates[28] demonstrated a strong correlation between the sodium concentration in plasma and the ratio total exchangeable sodium plus potassium, divided by the total body water. They also emphasized that the total body water appears to be passively distributed in proportion to osmotic activity and that all or almost all of body potassium is osmotically active, assumptions at variance with some newer data.[29] There is, however, a weakness in this analysis, which may become apparent when lean body-mass catabolism occurs. The focus of the problem is how the composition of the ICF changes when potassium ions leave ICF. This complex discussion is summarized in Figs. 4 to 6 and can be found elsewhere.[30] One can summarize the concepts outlined in Fig 4 to 6 as follows: in patients suffering from intense cell catabolism, the equation for the tonicity of the urine should be 2[Na + K] - [H₂PO₄], (2 times sodium plus potassium, minus phosphate) rather than simply 2[Na + K](2 times sodium plus potassium). However, in most other settings, the contribution of urinary phosphates is small and can be ignored.

One other constituent of the urine, urinary ammonium ions, should be considered. If ammonium ions are excreted along with chloride, does this change the number of effective osmoles in the body? Since ammonium ions are ultimately derived from macromolecules (proteins), their excretion has no direct impact on the tonicity of body fluids. Further, since ammonium ions are produced along with bicarbonate ions,[31] and these bicarbonate ions are added to the body in a 1:1 ratio when chloride ions are excreted, the excretion of ammonium and chloride (as distinct from sodium and chloride), does not contribute to a change in the number of "effective" particles in the body. Hence, urinary ammonium ion excretion, with or without chloride, does not have an appreciable impact on body tonicity and can be ignored.

The concept of body tonicity balance provided here can be simply put (Fig 7 ). If the water intake is different from what is needed for sodium and potassium intakes to be isotonic, total intakes ([Na + K]_in/water_in sodium plus potassium intake, divided bywater intakes) are hypotonic or hypertonic. For tonicity balance, the urinary loss must adapt to and reflect the deviation of intakes from isotonicity. Intakes are usually hypotonic, and, in normal subjects, the EWC represents the water intake that exceeds what is needed to incorporate the sodium and potassium intakes in the body without changing body tonicity. Conversely, a negative EWC represents the correct kidney adaptation to hypertonic intakes. Changes in tonicity balance indicate changes in ICF volume.

Conclusions

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Appendix 1

Acknowledgements

We thank Ms. Christelle Creusat for her excellent graphical assistance, Dr. Martin Schreiber for very helpful suggestions and constructive critique during the preparation of this manuscript and Jolly Mangat for expert secretarial assistance.

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