edited_Berl.qxp 13/7/09 04:40 Page 26
Renal Function
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.
50
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
51
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.
52
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
1. Adrogue HJ, Madias NE, N Engl J Med, 2000;342:1581–9. 19. Schrier RW, J Am Soc Nephrol, 2007;18:2028–31. 36. Gines A, Escorsell A, Gines P, et al., Gastroenterology,
2. Anderson RJ, Chung HM, Kluge R, Schrier RW, Ann Intern Med, 20. Lee WH, Packer M, Circulation, 1986;73:257–67. 1993;105:229–36.
1985;102:164–8. 21. Klein L, O’Connor CM, Leimberger JD, et al., Circulation, 37. Guyader D, Patat A, Ellis-Grosse EJ, Orczyk GP, Hepatology,
3. Hawkins RC, Clin Chim Acta, 2003;337:169–72. 2005;111:2454–60. 2002;36:1197–1205.
4. Miller M, Geriatrics, 1998;53:32–3, 37–8, 41–2 passim. 22. Szatalowicz VL, Arnold PE, Chaimovitz C, et al., N Engl J Med, 38. Wong F, Blei AT, Blendis LM, Thuluvath PJ, Hepatology,
5. Hoorn EJ, Lindemans J, Zietse R, Nephrol Dial Transplant, 1981;305:263–6. 2003;37:182–91.
2006;21:70–76. 23. Xu DL, Martin PY, Ohara M, et al., J Clin Invest, 39. Gerbes AL, Gulberg V, Gines P, et al., Gastroenterology,
6. Renneboog B, Musch W, Vandemergel X, et al., Am J Med, 1997;99:1500–5. 2003;124:933–9.
2006;119:71,e1–8. 24. Nielsen S, Terris J, Andersen D, et al., Proc Natl Acad Sci U S A, 40. Gines P, Wong F, Watson H, et al., Hepatology, 2008;48:204–13.
7. Gankam Kengne F AC, Sattar L, Melot C, Decaux G, QJM, 1997;94:5450–55. 41. Fujisawa G, Ishikawa S, Tsuboi Y, et al., Kidney International,
2008:583–8. 25. Nielsen S, Frokiaer J, Marples D, et al., Physiol Rev, 2002;82: 1993;44:19–23.
8. Verbalis J, Personal communication, 2005. 205–44. 42. Saito T, Ishikawa S, Abe K, et al., J Clin Endocrinol Metab,
9. Du Vigneaud V, The Harvey Lectures, 1954–55, New York: 26. Martin PY, Abraham WT, Lieming X, et al., J Am Soc Nephrol, 1997;82:1054–7.
Academic Press, 1956:1. 1999;10:2165–70. 43. Decaux G, J Lab Clin Med, 2001;138:18–21.
10. Manning M, Sawyer WH, J Lab Clin Med, 1989;114:617–32. 27. Abraham WT, Shamshirsaz AA, McFann K, et al., J Am Coll 44. Soupart A, Gross P, Legros JJ, et al., Clin J Am Soc Nephrol,
11. Zaoral M, Kolc J, Sorm F, Coll Czech Chem Commun, Cardiol, 2006;47:1615–21. 2006;1:1154–60.
1967;32:1250–57. 28. Gheorghiade M, Niazi I, Ouyang J, et al., Circulation, 45. Ghali JK, Koren MJ, Taylor JR, et al., J Clin Endocrinol Metab,
12. Kinter LB, Ilson BE, Caltabianol S, Vasopressin Third International 2003;107:2690–96. 2006;91:2145–52.
Vasopressin Conference, Paris: John Libbey Eurotext, 29. Gheorghiade M, Gattis WA, O’Connor CM, et al., JAMA, 46. Annane D, Decaux G, Smith N, Am J Med Sci, 2009;337:28–36.
1991:321–9. 2004;291:1963–71. 47. Walter KA, Am J Health Syst Pharm, 2007;64:1385–95.
13. Ohnishi A, Orita Y, Okahara R, et al., J Clin Invest, 30. Schrier RW, Gross P, Gheorghiade M, et al., N Engl J Med, 48. Zeltser D, Rosansky S, van Rensburg H, et al., Am J Nephrol,
1993;92:2653–9. 2006;355:2099–2112. 2007;27:447–57.
14. Schrier RW, J Am Soc Nephrol, 2006;17:1820–32. 31. Konstam MA, Gheorghiade M, Burnett Jr JC, et al., JAMA, 49. Berl T GP, et al., J Am Soc Nephrol Abstract, 2009; in press.
15. Greenberg A, Verbalis JG, Kidney International, 2007;297:1319–31. 50. Robertson GL, Aycinena P, Zerbe RL, Am J Med,
2006;69:2124–30. 32. Gheorghiade M, Konstam MA, Burnett Jr JC, et al., JAMA, 1982;72:339–53.
16. Yamamura Y, Ogawa H, Yamashita H, et al., British Journal of 2007;297:1332–43. 51. Feldman BJ, Rosenthal SM, Vargas GA, et al., N Engl J Med,
Pharmacology, 1992;105:787–91. 33. Udelson JE, Smith WB, Hendrix GH, et al., Circulation, 2005;352:1884–90.
17. Tahara A, Tomura Y, Wada KI, et al., J Pharmacol Exp Ther, 2001;104:2417–23. 52. Decaux G, Vandergheynst F, Bouko Y, et al., J Am Soc Nephrol,
1997;282:301–8. 34. Udelson JE, McGrew FA, Flores E, et al., J Am Coll Cardiol, 2007;18:606–12.
18. Macion-Dazard R, Callahan N, Xu Z, et al., J Pharmacol Exp Ther, 2007;49:2151–9.
2006;316:564–71. 35. Gines P, Guevara M, Hepatology, 2008;48:1002–10.
26 US NEPHROLOGY
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92