Thiazides for Hypervolemic Hypernatremia: A Valid Therapeutic Strategy?

Correspondence LETTERS TO THE EDITOR Understanding Hypernatremia To the Editor: The case report and discussion of Al-Absi et al1 is of interest for demonstrating the development of hypernatremia in one patient in the presence of volume overload and with volume depletion. However, some points in the discussion may be considered. First, in Fig 1 in the article, the closed circles presumably are meant to indicate solute, not sodium; cellular sodium concentration is ⬃10 mEq/L. The bulk of cell cation is potassium. Second, it is not clear that hypernatremia in the presence of volume overload results in cellular dehydration. Insofar as totalbody water is high and cells remain isosmolar to plasma, cell volume may be increased. High extracellular volume plus high cellular volume might help explain why antidiuretic hormone may not be maximal, urine osmolality is not maximal, and sodium excretion is maintained (see the first table in2). Third, by definition, in euvolemic hypernatremia, total water status is normal, not reduced. Thus, hypernatremia in extracellular fluid reflects salt overload, not loss of water, and total-body sodium level is high. Therefore, treatment should not rely on water loading, which, if effective, may produce water overload. Unless serum sodium level is ⬎150 mEq/L, probably no therapy is necessary. Fourth, in careful balance studies in healthy men, the difference between water intake and urine volume was ⬃1,500 mL,3,4 which suggests that this may be a better index of “insensible” water loss than the commonly used value of 500 mL. In sick patients, insensible water loss has not been studied to my knowledge. Finally, hypernatremia with volume overload is not uncommon and frequently is maintained despite efforts to lower the sodium concentration with hypotonic fluid administration.5,6 As the authors indicate, weight is a critical observation in diagnosing and treating hypernatremia appropriately.

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Thiazides for Hypervolemic Hypernatremia: A Valid Therapeutic Strategy? To the Editor: I congratulate Al-Absi et al1 on an excellent review of the concepts and management of hypernatremia. As the authors point out, when hypervolemic hyponatremia is encountered, sodium-rich urine must be diuresed in an attempt to induce a negative sodium balance in excess of the negative water balance to bring down plasma sodium level and subsequently total-body volume. Could this goal not be achieved better with thiazide-group diuretics, either alone or alternating with loop diuretics? By promoting proximal water reabsorption and upregulating distal aquaporin 2 channels, thiazides might help avoid the need to give simultaneous hypotonic infusions, especially in outpatients and/or nursing home residents.2,3 Madhav C. Menon, MD Mount Sinai School of Medicine New York, New York

Acknowledgements Financial Disclosure: The author declares that he has no relevant financial interests.

References

Acknowledgements

1. Al-Absi A, Gosmanova EO, Wall BM. A clinical approach to the treatment of chronic hypernatremia. Am J Kidney Dis. 2012; 60(6):1032-1038. 2. Makaryus AN, McFarlane SI. Diabetes insipidus: diagnosis and treatment of a complex disease. Cleve Clin J Med. 2006;73(1): 65-71. 3. Kim GH, Lee JW, Oh YK, et al. Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl cotransporter, and epithelial sodium channel. J Am Soc Nephrol. 2004;15(11):2836-2843.

Financial Disclosure: The author declares that he has no relevant financial interests.

© 2013 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2013.01.032

Thomas Kahn, MD Bronx VA Medical Center New York, New York

References 1. Al-Absi A, Gosmanova EO, Wall B. A clinical approach to the treatment of chronic hypernatremia. Am J Kidney Dis. 2012;60: 1032-1038. 2. Kahn T. Hypernatremia with edema. Arch Intern Med. 1999; 159:93-98. 3. Leach CS, Leonrad JI, Rambaut PC, Johnson PC. Evaporative water loss in man in a gravity-free environment. J Appl Physiol. 1978;45:430-436. 4. Heer M, Baisch F, Kropp J, Gerzer R, Drummer C. High dietary sodium chloride consumption may not induce body fluid retention in humans. Am J Physiol Renal Physiol. 2000;278:F585F595. 5. Hoorn EJ, Betjes MGH, Weigel J, Zietse R. Hypernatremia in critically ill patients: too little water and too much salt. Nephrol Dial Transplant. 2008;23:136-143. 6. Kahn T. Hypernatremia without water depletion. Clin Nephrol. 2011;76:130-135. Am J Kidney Dis. 2013;61(6):1041-1048

In Reply to ’Understanding Hypernatremia’ and ’Thiazides for Hypervolemic Hypernatremia: A Valid Therapeutic Strategy?’ In reply to Dr Kahn,1 hypervolemic hypernatremia requires disproportionate elevations of total-body sodium content relative to total-body water. Because sodium is largely restricted to the extracellular compartment, water achieves osmotic equilibrium by moving from intracellular to extracellular space. The net result is that the extracellular space expands, total-body water is elevated, and intracellular fluid volume is decreased.2 These changes are most likely to occur in skeletal muscle, which has limited acute cell volume regulatory mechanisms compared with brain cells.3 Dr Kahn raises an important observation that in sustained hypervolemic hypernatremia, cell volume regulatory mechanisms may lead to expansion of both intracellular and extracellular fluid volumes.4,5 To our knowledge, this hypothesis has not been tested directly. 1041