Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-10T12:49:12.693Z Has data issue: false hasContentIssue false

Hyponatraemia in older patients: a clinical and practical approach

Published online by Cambridge University Press:  16 January 2015

I Runkle*
Affiliation:
Endocrinology and Nutrition Department and Innovation Unit, Hospital Clínico San Carlos, Madrid
E Gomez-Hoyos
Affiliation:
Hospital Clínico Universitario de Valladolid, Valladolid, Spain
M Cuesta-Hernández
Affiliation:
Endocrinology Department. Beaumont Hospital, Dublin, Ireland
J Chafer-Vilaplana
Affiliation:
Endocrinology and Nutrition Department and Innovation Unit, Hospital Clínico San Carlos, Madrid
P de Miguel
Affiliation:
Endocrinology and Nutrition Department and Innovation Unit, Hospital Clínico San Carlos, Madrid
*
Address for correspondence: Dr Isabelle Runkle, c/Martin Lagos s/n, Madrid, 28040, Spain. Email: isabelle.runkle@salud.madrid.org

Summary

Hyponatraemia is frequent in older people and induces marked motor and cognitive dysfunction, even in patients deemed ‘asymptomatic’. Nutritional status is worse than in euvolaemic-matched controls, and the risk of fracture is increased following incidental falls. Yet hyponatraemia is undertreated, in spite of the fact that its correction is accompanied by a clear improvement in symptoms. Both evaluation of neurological symptoms and classification by volaemia are essential for a correct diagnosis and treatment of the hyponatraemic elderly patient. The syndrome of inappropriate anti-diuretic hormone secretion (SIADH) is the most common cause of hyponatraemia in older people. Nutritional status and chronicity of SIADH should be taken into account when deciding therapy. We propose an 8-step approach to the management of the elderly patient with hyponatraemia.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Miller, M, Hecker, MS, Friedlander, DA, Carter, JM. Apparent idiopathic hyponatremia in an ambulatory geriatric population. J Am Geriatr Soc 1996; 44: 404–8.CrossRefGoogle Scholar
2Lindner, G, Pfortmüller, C, Leichtle, A, Fielder, G, Exadaktylos, A. Age-related variety in electrolyte levels and prevalence of dysnatremias and dyskalemias in patients presenting to the emergency department. Gerontology 2014; published online 20 May 2014. doi: 10.1159/000360134.CrossRefGoogle ScholarPubMed
3Mannesse, CK, Vondeling, AM, van Marum, RJ, van Solinge, WW, Egberts, TC, Jansen, PA. Prevalence of hyponatremia on geriatric wards compared to other settings over four decades: A systematic review. Ageing Res Rev 2013; 12: 165–73.CrossRefGoogle ScholarPubMed
4Miller, M. Hyponatremia: age-related risk factors and therapy decisions. Geriatrics 1998; 53: 3233, 37–38, 41–42.Google ScholarPubMed
5Verbalis, J, Goldsmith, S, Greenberg, A, Korzelius, C, Schrier, R, Sterns, R, Thompson, C. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med 2013; 126 (D suppl 1): S142.CrossRefGoogle ScholarPubMed
6Spasovski, G, Vanholder, R, Allolio, B, Annane, D, Ball, S, Bichet, D, Decaux, G, Fenske, W, Hoorn, E, Ichai, C, Joannidis, M, Soupart, A, Zietse, R, Haller, M, van der Veer, S, Van Biesen, W, NAgler, E. Clinical practice guideline and diagnosis and treatment of hyponatremia. EJE 2014; 170: G147.CrossRefGoogle Scholar
7Runkle, I, Villabona, C, Navarro, A, Pose, A, Formiga, F, Tejedor, A, Poch, E. El tratamiento de la hiponatremia secundaria al síndrome de secreción inadecuada de la hormona antidiurética. Medicina Clínica 2013; 141: 507.CrossRefGoogle Scholar
8Shapiro, D, Sonnenblick, M, Galperin, I, Melkonyan, L, Munter, G. Severe hyponatraemia in elderly hospitalized patients: prevalence, aetiology and outcome. Int Med J 2010; 40: 574580.CrossRefGoogle ScholarPubMed
9Cowen, L, Hodak, S, Verbalis, J. Age-associated abnormalities of water homeostasis. Endocrinol Metab Clin North Am 2013; 42: 349–70.CrossRefGoogle ScholarPubMed
10Beck, LH. Changes in renal function with aging. Clin Geriatr Med 1998; 14: 199209.CrossRefGoogle ScholarPubMed
11Rolls, BJ, Phillips, PA. Aging and disturbances of thirst and fluid balance. Nutr Rev 1990; 48: 137–44.CrossRefGoogle ScholarPubMed
12Rao, MY, Sudhir, U, Anil Kumar, T, Saravanan, S, Mahesh, E, Punith, K. Hospital-based descriptive study of symptomatic hyponatremia in elderly patients. J Assoc Physicians India 2010; 58: 667–69.Google ScholarPubMed
13Anpalahan, M. Chronic idiopathic hyponatremia in older people due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) possibly related to aging. J Am Geriatr Soc 2001; 49: 788–92.CrossRefGoogle ScholarPubMed
14Hirshberg, B, Ben-Yehuda, A. The syndrome of inappropriate antidiuretic hormone secretion in the elderly. Am J Med 1997; 103: 270–73.CrossRefGoogle ScholarPubMed
15Arinzon, Z, Feldman, J, Jarchowsky, J, Fidelman, Z, Krasnyansky, I, Adunsky, A. A comparative study of the syndrome of inappropriate antidiuretic hormone secretion in community-dwelling patients and nursing home residents. Aging Clin Exp Res 2003; 15: 611.CrossRefGoogle ScholarPubMed
16Hillier, A, Abbot, R, Barrett, B. Hyponatremia: Evaluating the correction factor for hyperglycemia. Am J Med 1999; 106: 399403.CrossRefGoogle ScholarPubMed
17Liamis, G, Liberopoulos, E, Barkas, F, Elisaf, M. Spurious electrolyte disorders: a diagnostic challenge for clinicians. Am J Nephrol 2013; 38: 5055.CrossRefGoogle ScholarPubMed
18Chow, E, Fox, N, Gama, R. The effect of low serum total protein on sodium and potassium measurement by ion-selective electrodes in critically ill patients. Br J Biomed Sci 2008; 65: 128–31.CrossRefGoogle ScholarPubMed
19Wald, R, Jaber, B, Price, LL, Upadhyay, A, Madias, N. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med 2010; 170: 294.CrossRefGoogle ScholarPubMed
20Leung, A, McAlister, F, Rogers, S, Pazo, V, Wright, A, Bates, D. Preoperative hyponatremia and perioperative complications. Arch Intern Med 2012; 172: 1474–81.CrossRefGoogle ScholarPubMed
21Nzerue, C, Bonnie, H, You, W, Falana, B, Dai, S. Predictors of outcome in hospitalized patients with severe hyponatremia. J Natl Med Assoc 2003; 95: 335–43.Google ScholarPubMed
22Ayus, JC, Arieff, AI. Chronic hyponatremic encephalopathy in postmenopausal women: association of therapies with morbidity and mortality. JAMA 1999; 281: 2299–304.CrossRefGoogle ScholarPubMed
23Renneboog, B, Musch, W, Vandemergel, X, Manto, MU, Decaux, G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 2006; 119: 71.CrossRefGoogle ScholarPubMed
24Gosch, M, Joosten-Gstrein, B, Heppner, HJ, Lechleitner, M. Hyponatremia in geriatric inhospital patients: effects on results of a comprehensive geriatric assessment. Gerontology 2012; 58: 430–40.CrossRefGoogle ScholarPubMed
25Verbalis, JG, Barsony, J, Sugimura, Y, Tian, Y, Adams, DJ, Carter, EAet al.Hyponatremia-induced osteoporosis. J Bone Miner Res 2010; 25: 554–63.CrossRefGoogle ScholarPubMed
26Hoorn, EJ, Rivadeneira, F, van Meurs, JB, Ziere, G, Stricker, BH, Hofman, A, Pols, HA, Zietse, R, Uitterlinden, AG, Zillikens, MC. Mild hyponatremia as a risk factor for fractures: the Rotterdam study. J Bone Miner Res 2011; 26: 1822–28.CrossRefGoogle ScholarPubMed
27Rodenburg, EM, Hoorn, EJ, Ruiter, R, Lous, JJ, Hofman, A, Uitterlinden, AG, Stricker, BH, Visser, LE. Thiazide-associated hyponatremia: a population-based study. Am J Kidney Dis 2013; 62: 6772.CrossRefGoogle ScholarPubMed
28Tolouian, R, Alhamad, T, Farazmand, M, Mulla, ZD. The correlation of hip fracture and hyponatremia in the elderly. J Nephrol 2012; 25: 789–93.CrossRefGoogle ScholarPubMed
29Wald, R, Jaber, BL, Price, LL, Upadhyay, A, Madias, NE. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med 2010; 170: 294302.CrossRefGoogle ScholarPubMed
30Waikar, SS, Mount, DB, Curhan, GC. Mortality after hospitalization with mild, moderate, and severe hyponatremia. Am J Med 2009; 122: 857–65.CrossRefGoogle ScholarPubMed
31Hoorn, EJ, Lindemans, J, Zietse, R. Development of severe hyponatraemia in hospitalized patients: treatment-related risk factors and inadequate management. Nephrol Dial Transplant 2006; 21: 7076.CrossRefGoogle ScholarPubMed
32Movafagh, S, Cleemann, L, Morad, M. Regulation of cardiac Ca2 +channel by extracellular Na+. Cell Calcium 2011; 49: 162–73.CrossRefGoogle ScholarPubMed
33Arao, K, Fujiwara, T, Sakakura, K, Wada, H, Sugawara, Y, Suga, C, Ako, J, Ishikawa, SE, Momomura, S. Hyponatremia as a predictor for worsening heart failure in patients receiving cardiac resynchronization therapy. Circ J 2013; 77: 116–22.CrossRefGoogle ScholarPubMed
34Hauptman, PJ, Burnett, J, Gheorghiade, M, Grinfeld, L, Konstam, MA, Kostic, D, Krasa, HB, Maggioni, A, Ouyang, J, Swedberg, K, Zannad, F, Zimmer, C, Udelson, JE. Clinical course of patients with hyponatraemia and decompensated systolic heart failure and the effect of vasopressin receptor antagonism with tolvaptan. J Card Fail 2013; 19: 390–97.CrossRefGoogle ScholarPubMed
35Nielsen, S, Fror, J, Knepper, MA. Renal aquaporins: key roles in water balance and water balance disorders. Curr Opin Nephrol Hypertens 1998; 7: 509–16.CrossRefGoogle ScholarPubMed
36Wong, LL, Verbalis, JG. Systemic diseases associated with disorders of water homeostasis. Endocrinol Metab Clin North Am 2002; 31: 121–40.CrossRefGoogle ScholarPubMed
37Verbalis, J. Whole-body volume regulation and escape from antidiuresis. Am J Med 2006; 119: S2129.CrossRefGoogle ScholarPubMed
38Sharabi, Y, Illan, R, Kamari, Y, Cohen, H, Nadler, M, Messerli, FH, Grossman, E. Diuretic induced hyponatraemia in elderly hypertensive women. J Hum Hypertens 2002; 16: 631–35.CrossRefGoogle ScholarPubMed
39Leung, AA, Wright, A, Pazo, V, Karson, A, Bates, DW. Risk of thiazide-induced hyponatremia in patients with hypertension. Am J Med 2011; 124: 1064–72.CrossRefGoogle ScholarPubMed
40Clark, BA, Shannon, RP, Rosa, RM, Epstein, FH. Increased susceptibility to thiazide-induced hyponatremia in the elderly. J Am Soc Nephrol 1994; 5: 1106–11.CrossRefGoogle ScholarPubMed
41Kim, GH, Lee, JW, Oh, YK, Chang, HR, Joo, KW, Na, KY, Earm, JH, Knepper, MA, Han, JS. Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na–Cl co-transporter, and epithelial sodium cannel. J Am Soc Nephrol 2004; 15: 2836–43.CrossRefGoogle Scholar
42Rastogi, D, Pelter, MA, Deamer, RL. Evaluations of hospitalizations associated with thiazide-associated hyponatremia. J Clin Hypertens (Greenwich) 2012; 14: 158–64.CrossRefGoogle ScholarPubMed
43Yamada, H, Asano, T, Aoki, A, Ikoma, A, Yoshida, M, Kusaka, I, Kawakami, M, Kakei, M, Ishikawa, SE. Combination therapy of angiotensin II receptor blocker and thiazide produces severe hyponatremia in elderly hypertensive subjects. Intern Med 2014; 53: 749–52.CrossRefGoogle ScholarPubMed
44Crespo Hernández, I, Ruiz Gracia, T, Gomez Hoyos, E, Ortola Buigues, A, Cuesta Hernandez, M, Fernandez Capel, F, de Miguel Novoa, P, Sanabria Perez, MC, Calle Pascual, A, Runkle de la Vega, I. Marked thiazide-induced hyponatremia: characteristics of a group of patients. 16th European Congress of Endocrinology (Wroclaw, Poland), 723.Google Scholar
45Talapatra, I, Kalavalapalli, S, Tymms, DJ. Isolated hypoaldosteronism: an overlooked cause of hyponatraemia. Eur J Internal Med 2007; 18: 246–48.CrossRefGoogle ScholarPubMed
46Gómez Hoyos, E, Montañez Zorrilla, C, Cuesta Hernández, C, de Miguel Novoa, P, Pelaz Berdullas, L, Matía Martín, P, Marcuello Foncillas, C, Pérez Ferre, N, Calle Pascual, A, Runkle de la Vega, I. Pacientes con hipovolemia, hiponatremia e hipokaliemia en límites altos: pensar en hipoaldosteronismos tras descartar enfermedad de Addison. Abs, no. 21. XI Congreso de la Sociedad de Endocrinología, Nutrición y Diabetes de la Comunidad de Madrid (SENDIMAD), November 2012.Google Scholar
47Haas, CS, Pohlenz, I, Lindner, U, Muck, PM, Arand, J, Suefke, S, Lehnert, H. Renal tubular acidosis type IV in hyperkalaemic patients – a fairy tale or reality? Clin Endocrinol (Oxford) 2013; 78: 706–11.CrossRefGoogle ScholarPubMed
48Choi, MJ, Ziyadeh, FN. The utility of the transtubular potassium gradient in the evaluation of hyperkalemia. J Am Soc Nephrol 2008; 19: 424–26.CrossRefGoogle ScholarPubMed
49Bhaskar, B, Fraser, JF, Mullaney, D. Lest we forget: heparin-induced hyperkalemia. J Cardiothorac Vasc Anesth 2012; 26: 106–9.CrossRefGoogle ScholarPubMed
50Hannon, MJ, Behan, LA, O’Brien, MM, Tormey, W, Ball, SG, Javadpour, M, Sherlock, M, Thompson, CJ. Hyponatremia following mild/moderate subarachnoid hemorrhage is due to SIAD and glucocorticoid deficiency and not cerebral salt wasting. J Clin Endocrinol Metab 2014; 99: 291–98.CrossRefGoogle Scholar
51Robertson, G. Regulation of arginine vasopressin in the syndrome of inappropriate antidiuresis. Am J Med 2006; 119: S36–42.CrossRefGoogle ScholarPubMed
52Sands, J, Layton, H. The physiology of urine concentration: an update. Seminars in Nephrology 2009; 29: 178–95.CrossRefGoogle ScholarPubMed
53Janicic, N, Verbalis, JG. Evaluation and management of hypo-osmolality in hospitalized patients. Endocrinol Metab Clin North Am 2003; 32: 459–81.CrossRefGoogle ScholarPubMed
54Kovács, KJ, Földes, A, Sawchenko, PE. Glucocorticoid negative feedback selectively targets vasopressin transcription in parvocellular neurosecretory neurons. J Neurosci 2000; 20: 3843–52.CrossRefGoogle ScholarPubMed
55Aguilera, G, Liu, Y. The molecular physiology of CRH neurons. Frontiers in Neuroendocrinology 2012; 33: 6784.CrossRefGoogle ScholarPubMed
56Suzuki, H, Kawasaki, M, Ohnishi, H, Otsubo, H, Ohbuchi, T, Katoh, A, Hashimoto, H, Yokoyama, T, Fujihara, H, Dayanithi, G, Murphy, D, Nakamura, T, Ueta, Y. Exaggerated response of a vasopressin-enhanced green fluorescent protein transgene to nociceptive stimulation in the rat. J Neurosci 2009; 29: 13182–89.CrossRefGoogle ScholarPubMed
57Sherlock, M, O’Sullivan, E, Agha, A, Behan, LA, Rawluk, D, Brennan, P, Tormey, W, Thompson, CJ. The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage. Clin Endocrinol 2006; 64: 250–54.CrossRefGoogle ScholarPubMed
58Maesaka, JK, Gupta, S, Fishbane, S. Cerebral salt-wasting syndrome: does it exist? Nephron 1999; 82: 100–9.CrossRefGoogle ScholarPubMed
59Palmer, BF. Hyponatremia in patients with central nervous system disease: SIADH versus CSW. Trends Endocrinol Metab 2003; 14: 182–87.CrossRefGoogle ScholarPubMed
60Berl, T. Impact of solute intake on urine flow and water excretion. J Am Soc Nephrol 2008; 19: 1076–78.CrossRefGoogle ScholarPubMed
61Cherney, DZ, Davids, MR, Halperin, ML. Acute hyponatraemia and ‘ecstasy’: insights from a quantitative and integrative analysis. QJM 2002; 95: 475–83.CrossRefGoogle ScholarPubMed
62Shafiee, MA, Charest, AF, Cheema-Dhadli, S, Glick, DN, Napolova, O, Roozbeh, J, Semenova, E, Sharman, A, Halperin, ML. Defining conditions that lead to the retention of water: the importance of the arterial sodium concentration. Kidney Int 2005; 67: 613.CrossRefGoogle Scholar
63Gómez Hoyos, E, Matía Martin, P, Cuesta Hernández, M, Hernández Núñez, G, Larrad Saiz, A, Soria Carreras, P, Pérez Ferre, N, Cabrerizo Garcia, L, Rubio Herrera, MA, Runkle de la Vega, I. Prevalencia e Incidencia de Hiponatremia en pacientes con soporte nutricional artificial por vía parenteral. XXVIII Congreso Nacional SENPE (Sociedad Española de Nutrición Enteral y Parenteral). Oviedo. Nutrición Hospitalaria 28, suppl 3; May 2013.Google Scholar
64Gómez Hoyos, E, Cuesta Hernández, M, Fernández Capel, F, Ruiz Gracia, T, Martín Matía, P, Rubio Herrera, MA, Cabrerizo García, L, Pérez Ferre, N, Calle Pascual, A, Runkle de la Vega, I. Diagnosis and management of patients presenting hyponatremia while receiving parenteral nutrition. Abs no. 437, poster 694. 15th European Congress of Endocrinology, Copenhagen, 27 April to 1 May 2013. Endocrine Abstracts 2013; 32: 694.Google Scholar
65Warner, MH, Holding, S, Kilpatrick, ES. The effect of newly diagnosed hypothyroidism on serum sodium concentrations: a retrospective study. Clin Endocrinol 2006; 64: 598–99.CrossRefGoogle ScholarPubMed
66Musch, W, Decaux, G. Treating the syndrome of inappropriate ADH secretion with isotonic saline. Q J Med 1998; 91: 749–53.CrossRefGoogle ScholarPubMed
67Hew-Butler, T, Almond, C, Ayus, JC, Dugas, J, Meeuwisse, W, Noakes, T, Reid, S, Siegel, A, Speedy, D, Stuempfle, K, Verbalis, J, Weschler, L. Exercise-Associated Hyponatraemia (EAH) Consensus Panel: Consensus statement of the 1st International Exercise-Associated Hyponatremia Consensus Development Conference, Cape Town, South Africa 2005. Clin J Sport Med 2005; 15: 208–13.CrossRefGoogle ScholarPubMed
68Sterns, R, Nigwekar, SU, Hix, JK. The treatment of hyponatremia. Seminars in Nephrology 2009; 29: 282–99.CrossRefGoogle ScholarPubMed
69Perianayagam, A, Sterns, R, Silver, S, Grieff, M, Mayo, R, Hix, J, Kouides, R. DDAVP is effective in preventing and reversing inadvertent overcorrection of hyponatremia. Clin J Am Soc Nephrol 2008; 3: 331–36.CrossRefGoogle ScholarPubMed
70Soupart, A, Penninckx, R, Crenier, L, Stenuit, A, Perier, O, Decaux, G. Prevention of brain demyelination in rats after excessive correction of chronic hyponatremia by serum sodium lowering. Kidney Int 1994; 45: 193.CrossRefGoogle ScholarPubMed
71Gankam Kengne, F, Soupart, A, Pochet, R, Brion, JP, Decaux, G. Re-induction of hyponatraemia after rapid overcorrection of hyponatremia reduces mortality in rats. Kidney Int 2009; 76: 614.CrossRefGoogle ScholarPubMed
72Perazella, M. Drug-induced hyperkalemia: old culprits and new offenders. Am J Med 2000; 109: 307–14.CrossRefGoogle ScholarPubMed
73Momi, J, Tang, CM, Abcar, AC, Kujubu, DA, Sim, JJ. Hyponatremia – what is cerebral salt wasting? Perm J 2010; 14: 6265.CrossRefGoogle ScholarPubMed
74Licata, G, Di Pasquale, P, Parrinello, G, Cardinale, A, Scandurra, A, Follone, G, Argano, C, Tuttolomondo, A, Paterna, S. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Am Heart J 2003; 145: 459–66.CrossRefGoogle ScholarPubMed
75Stratton, R, Hébuterne, X, Elia, M. A systematic review and meta-analysis of the impact of oral nutritional supplements on hospital readmissions. Ageing Res Rev 2013; 12: 884–97.CrossRefGoogle ScholarPubMed
76Gómez Hoyos, E, Cuesta Hernández, M, Ruíz Gracia, T, de Miguel Novoa, MP, Molino González, A, Díaz Pérez, JA, Calle Pascual, A, Runkle de la Vega, I. Manejo diagnóstico y terapéutico de la hiponatremia (HN) por el Síndrome de secreción inadecuada de ADH (SIADH) por el Servicio de Endocrinología y Nutrición (EN) del Hospital Clínico San Carlos. 55 Congreso de la SEEN, Granada, 15–17 May 2013.Google Scholar
77Furst, H, Hallows, KR, Post, J, Chen, S, Kotzker, W, Goldfarb, S, Ziyadeh, FN, Neilson, EG. The urine/plasma electrolyte ratio: a predictive guide to water restriction. Am J Med Sci 2000; 319: 240–44.CrossRefGoogle ScholarPubMed
78Decaux, G, Waterlot, Y, Genette, F, Hallemans, R, Demanet, JC. Inappropriate secretion of antidiuretic hormone treated with furosemide. Br Med J (Clin Res Ed) 1982; 285: 8990.CrossRefGoogle Scholar
79Decaux, G. Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by long loop diuretics. Nephron 1983; 35: 8288.CrossRefGoogle ScholarPubMed
80Cuesta, M, Gomez-Hoyos, E, Montañez, C, Martin, P, Marcuello, C, de Miguel, P, Calle, A, Runkle, I. An initial dose of 7.5 mg Tolvaptan is safe and effective in the treatment of hyponatremia caused by SIADH. 15th International Congress of Endocrinology jointly with the 14th European Congress of Endocrinology (Florencia, May 2012). Endocrine Abstracts 2012: 29: P1149.Google Scholar
81Runkle, I, Gomez Hoyos, E, Recio Blázquez, L, Cuesta Hernández, M, de Miguel Novoa, MP, Ruiz Gracia, T, Sanabria Perez, C, Santiago Perez, A, Matia Martin, P, Calle Pascual, A. Experiencia con una dosis inicial de 7.5 mg de tolvaptan en el tratamiento de la hiponatremia secundaria al SIADH. 56 congreso de la SEEN, Valencia, 21–23 May 2014.Google Scholar
82Torres, VE, Chapman, AB, Devuyst, O, Gansevoort, RT, Grantham, JJ, Higashihara, E, Perrone, RD, Krasa, HB, Ouyang, J, Czerwiec, FS; TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2012; 367: 2407–18.CrossRefGoogle Scholar
83Soupart, A, Coofernils, M, Couturier, B, Gankam-Kengne, F, Decaux, G. Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH. Clin J Am Soc Nephrol 2012; 7: 742–47.CrossRefGoogle ScholarPubMed
84Decaux, G, Andres, C, Gankam Kengne, F, Soupart, A. Treatment of euvolemic hyponatremia in the intensive care unit by urea. Critical Care 2010; 14: R184.CrossRefGoogle ScholarPubMed
85Vandergheynst, F, Brachet, C, Heinrichs, C, Decaux, G. Long-term treatment of hyponatremic patients with nephrogenic syndrome of inappropriate antidiuresis: personal experience and review of published case reports. Nephron Clin Pract 2012; 120: 168–72.CrossRefGoogle ScholarPubMed
86Fenske, WK, Christ-Crain, M, Hörning, A, Simet, J, Szinnai, G, Fassnacht, M, Rutishauser, J, Bichet, DG, Störk, S, Allolio, B. A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis. J Am Soc Nephrol 2014; 25: 2376–83.CrossRefGoogle ScholarPubMed
87Better, OS, Gonick, HC, Chapman, LC, Varrady, PD, Kleeman, CR. Effect of urea-saline diuresis on renal clearance of calcium, magnesium, and inorganic phosphate in man. Proc Soc Exp Biol Med 1966; 121: 592–96.CrossRefGoogle ScholarPubMed