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The measurement of plasma vasopressin in patients with SIADH water access. The drugs therefore possess many of the qualities a
undertaken by Robertson et al.
revealed that most had hormone levels clinician would be looking for in an ideal drug with which to treat these
in the ‘normal’ range, albeit at lower plasma osmolalities at which the hyponatremic conditions, and are clearly superior to all currently
levels should have been suppressed. Such patients would be expected to available treatments. However, there remain a number of questions that
respond to the vasopressin antagonists. There were, however, individuals require further assessment and data collection. It is not known whether
who had very high levels of the hormone, and it is conceivable that in the correction of the hyponatremia will have a significant impact on the
these patients the drugs would be less effective. Of interest is that in patient’s quality of life, cognitive function, rate of hospitalization, or
approximately 10% of patients the hormone was not measurable. The overall mortality in all of the described clinical settings. Will the drugs
report of two male infants with hyponatremia who had an increase of reduce subclinical dementia in elderly hyponatremic patients and
function mutations of the V2 receptor located on the X chromosome
decrease their risk for fractures by preventing falls? Will they improve
triggered the search for such a mutation in the adult population. cognition in patients with liver failure who have concomitant impending
Recently, Decaux et al.
reported on a family whose proband, a 74-year- hepatic encephalopathy? Finally, an assessment of the value of sole V2
old man with hyponatremia, was resistant to two different vasopressin receptor blockade versus combined V1a/V2 blockade is of interest,
receptor antagonists and who proved to have a mutation in the particularly in assessing whether V1a blockade would add to the effects
vasopressin receptor. Female carriers also had spontaneous episodes of of beta-adrenergic, renin–angiotensin, and aldosterone blockade in
hyponatremia. Such patients will be resistant to vasopressin antagonists. patients with advanced cardiac disease. Clearly, further clinical trials
directed at providing answers to these unanswered questions are still
Conclusions and Unanswered Questions very much needed. ■
The development of vasopressin antagonists (vaptans) and their advent
into clinical practice clearly portend a new era in the treatment of
Tomas Berl, MD, is a Professor of Medicine in the Division
hyponatremic disorders. Addressing the primary mechanism of the non-
of Renal Diseases and Hypertension at the University of
osmotic release of AVP that underlies these disorders is the most Colorado. He is the former Head of the Division of Renal
physiological of approaches to the enhancement of solute-free water
Disease and Hypertension at the University of Colorado
Health Sciences Center in Denver. Professor Berl is a
excretion and the correction of the electrolyte abnormality. Both an
member of several professional organizations and
intravenous (conivaptan) and an oral agent (tolvaptan) are currently societies, including the American Society of Clinical
available for hypervolemic and euvolemic patients with this electrolyte
Investigation (ASCI), the American Association of
Physicians (AAP), and the American Clinical and
disorder. The aquaretic agents provide a reliable, predictable, yet not
Climatological Society (ACCS). He was President of the American Society of Nephrology
excessive increase in serum sodium concentration without attendant (ASN) in 2005. Professor Berl has had continuous National Institutes of Health (NIH)
significant changes in sodium or potassium excretion. The use of these
funding for his research for more than 30 years, and has authored or co-authored more
than 215 peer-reviewed scientific articles, editorials, reviews, and book chapters.
drugs also appears to be free of significant adverse effects, in both
short- and long-term observations, and they allow patients to have freer
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