Sections

Hypernatremia

Medication

Medication Summary

Some patients with nephrogenic diabetes insipidus—particularly those in whom it is mild or incomplete—may benefit from diuretic therapy (eg, thiazides, loop-diuretics) in an effort to increase proximal tubular reabsorption and decrease delivery to diluting segments where water may be lost. Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the polyuria in these patients. In addition, any medications that may cause nephrogenic diabetes insipidus (such as lithium) may require discontinuation.

In patients with central diabetes insipidus, desmopressin administered orally or intranasally may be used. Pharmacologic agents can be used in partial central diabetes insipidus to increase circulating AVP. These drugs include chlorpropamide, clofibrate, and carbamazepine.

Class Summary

These drugs may be used to enhance sodium excretion.

Hydrochlorothiazide (Esidrix, HydroDiuril, Microzide)

View full drug information

Inhibits the reabsorption of sodium in the distal tubules, causing increased excretion of sodium and water, as well as of potassium and hydrogen ions.

Furosemide (Lasix)

View full drug information

Loop diuretic that increases excretion of water by interfering with chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Increases renal blood flow without increasing filtration rate. Onset of action generally is within 1-h. Increases potassium, sodium, calcium, and magnesium excretion.

Class Summary

These agents may enhance sodium excretion.

Desmopressin (DDAVP)

View full drug information

Increases cellular permeability of collecting ducts, resulting in the reabsorption of water by the kidneys.

Questions

Muhsin SA, Mount DB. Diagnosis and treatment of hypernatremia. Best Pract Res Clin Endocrinol Metab. 2016 Mar. 30 (2):189-203. [QxMD MEDLINE Link].
Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med. 2000 May 18. 342(20):1493-9. [QxMD MEDLINE Link].
Verbalis JG. Disorders of Water Balance. In:. Skorecki K, Chertow GM, Marsden PA, Yu ASL, Taal MW, eds. Brenner and Rector's The Kidney. 10th ed. Philadelphia, PA: Elsevier; 2016. 460-510.
Chumlea WC, Guo SS, Zeller CM, et al. Total body water data for white adults 18 to 64 years of age: the Fels Longitudinal Study. Kidney Int. 1999 Jul. 56(1):244-52. [QxMD MEDLINE Link].
Bhave G, Neilson EG. Body fluid dynamics: back to the future. J Am Soc Nephrol. 2011 Dec. 22(12):2166-81. [QxMD MEDLINE Link].
Sterns HR. Renal function and disorders of water and sodium balance. ACP Medicine: A Publication of the American College of Physicians. New York, NY: WebMD; 2005. 10.1-10.19.
Boone M, Deen PM. Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption. Pflugers Arch. 2008 Sep. 456(6):1005-24. [QxMD MEDLINE Link]. [Full Text].
Loh JA, Verbalis JG. Disorders of water and salt metabolism associated with pituitary disease. Endocrinol Metab Clin North Am. 2008 Mar. 37(1):213-34, x. [QxMD MEDLINE Link].
Thornton SN. Thirst and hydration: Physiology and consequences of dysfunction. Physiol Behav. 2010. 100:15-20. [QxMD MEDLINE Link].
Kumar S, Berl T. Sodium. Lancet. 1998 Jul 18. 352(9123):220-8. [QxMD MEDLINE Link].
Palevsky PM. Hypernatremia. Semin Nephrol. 1998 Jan. 18(1):20-30. [QxMD MEDLINE Link].
Hoefer D, Ruttmann-Ulmer E, Smits JM, et al. Donor hypo- and hypernatremia are predictors for increased 1-year mortality after cardiac transplantation. Transpl Int. 2009 Dec 14. [QxMD MEDLINE Link].
Hiyama TY, Matsuda S, Fujikawa A, et al. Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia. Neuron. 2010 May 27. 66(4):508-22. [QxMD MEDLINE Link].
Lin JJ, Lin KL, Hsia SH, et al. Combined central diabetes insipidus and cerebral salt wasting syndrome in children. Pediatr Neurol. 2009 Feb. 40(2):84-7. [QxMD MEDLINE Link].
Hureaux M, Vargas-Poussou R. Genetic basis of nephrogenic diabetes insipidus. Mol Cell Endocrinol. 2023 Jan 15. 560:111825. [QxMD MEDLINE Link].
Bockenhauer D, van't Hoff W, Dattani M, et al. Secondary nephrogenic diabetes insipidus as a complication of inherited renal diseases. Nephron Physiol. 2010. 116(4):p23-9. [QxMD MEDLINE Link].
Mavrakis AN, Tritos NA. Diabetes insipidus with deficient thirst: report of a patient and review of the literature. Am J Kidney Dis. 2008 May. 51(5):851-9. [QxMD MEDLINE Link].
Arzhan S, Roumelioti ME, Litvinovich I, Bologa CG, Myers OB, Unruh ML. Hypernatremia in Hospitalized Patients: A Large Population-Based Study. Kidney360. 2022 Jul 28. 3 (7):1144-1157. [QxMD MEDLINE Link]. [Full Text].
Tucker BM, Walther CP. Outcomes Associated with Hypernatremia at Admission in Hospitalized Persons. Kidney360. 2022 Jul 28. 3 (7):1122-1123. [QxMD MEDLINE Link]. [Full Text].
Tsipotis E, Price LL, Jaber BL, Madias NE. Hospital-Associated Hypernatremia Spectrum and Clinical Outcomes in an Unselected Cohort. Am J Med. 2018 Jan. 131 (1):72-82.e1. [QxMD MEDLINE Link].
Jung WJ, Lee HJ, Park S, Lee SN, Kang HR, Jeon JS, et al. Severity of community acquired hypernatremia is an independent predictor of mortality. Intern Emerg Med. 2017 Oct. 12 (7):935-940. [QxMD MEDLINE Link].
Lindner G, Funk GC, Schwarz C, et al. Hypernatremia in the critically ill is an independent risk factor for mortality. Am J Kidney Dis. Dec 2007. 50(6):952-7. [QxMD MEDLINE Link].
Stelfox HT, Ahmed SB, Khandwala F, et al. The epidemiology of intensive care unit acquired hyponatremia and hypernatremia in medical-surgical intensive care units. Crit Care. 2008 Dec 18. 12(6):R162. [QxMD MEDLINE Link]. [Full Text].
Hawkins RC. Age and gender as risk factors for hyponatremia and hypernatremia. Clin Chim Acta. 2003 Nov. 337(1-2):169-72. [QxMD MEDLINE Link].
Lavagno C, Camozzi P, Renzi S, Lava SA, Simonetti GD, Bianchetti MG, et al. Breastfeeding-Associated Hypernatremia: A Systematic Review of the Literature. J Hum Lact. 2016 Feb. 32 (1):67-74. [QxMD MEDLINE Link].
Wilde VK. Breastfeeding Insufficiencies: Common and Preventable Harm to Neonates. Cureus. 2021 Oct. 13 (10):e18478. [QxMD MEDLINE Link]. [Full Text].
Darmon M, Timsit JF, Francais A, et al. Association between hypernatraemia acquired in the ICU and mortality: a cohort study. Nephrol Dial Transplant. 2010 Feb 17. [QxMD MEDLINE Link].
Funk GC, Lindner G, Druml W, et al. Incidence and prognosis of dysnatremias present on ICU admission. Intensive Care Med. 2010 Feb. 36(2):304-11. [QxMD MEDLINE Link].
Ates I, Özkayar N, Toprak G, Yılmaz N, Dede F. Factors associated with mortality in patients presenting to the emergency department with severe hypernatremia. Intern Emerg Med. 2016 Apr. 11 (3):451-9. [QxMD MEDLINE Link].
Kumar AB, Shi Y, Shotwell MS, Richards J, Ehrenfeld JM. Hypernatremia is a Significant Risk Factor for Acute Kidney Injury After Subarachnoid Hemorrhage: A Retrospective Analysis. Neurocrit Care. 2014 Sep 18. [QxMD MEDLINE Link].
VAN DE Louw A, Shaffer C, Schaefer E. Early intensive care unit-acquired hypernatremia in severe sepsis patients receiving 0.9% saline fluid resuscitation. Acta Anaesthesiol Scand. 2014 Sep. 58(8):1007-14. [QxMD MEDLINE Link].
Leung AA, McAlister FA, Finlayson SR, Bates DW. Preoperative hypernatremia predicts increased perioperative morbidity and mortality. Am J Med. 2013 Oct. 126(10):877-86. [QxMD MEDLINE Link].
Zimmer MA, Zink AK, Weißer CW, Vogt U, Michelsen A, Priebe HJ, et al. Hypernatremia-A Manifestation of COVID-19: A Case Series. A A Pract. 2020 Jul. 14 (9):e01295. [QxMD MEDLINE Link]. [Full Text].
Song HJJMD, Chia AZQ, Tan BKJ, Teo CB, Lim V, Chua HR, et al. Electrolyte imbalances as poor prognostic markers in COVID-19: a systemic review and meta-analysis. J Endocrinol Invest. 2022 Sep 7. 11:1-25. [QxMD MEDLINE Link]. [Full Text].
Toklu H, Ganti L, Crimi E, Cintron C, Hagan J, Serrano E. Cerebrospinal fluid findings and hypernatremia in COVID-19 patients with altered mental status. Int J Emerg Med. 2020 Dec 9. 13 (1):63. [QxMD MEDLINE Link]. [Full Text].
Zimmer MA, Zink AK, Weißer CW, Vogt U, Michelsen A, Priebe HJ, et al. Hypernatremia-A Manifestation of COVID-19: A Case Series. A A Pract. 2020 Jul. 14 (9):e01295. [QxMD MEDLINE Link]. [Full Text].
Herrod PJ, Awad S, Redfern A, et al. Hypo- and hypernatraemia in surgical patients: is there room for improvement?. World J Surg. 2010 Mar. 34(3):495-9. [QxMD MEDLINE Link].
Chassagne P, Druesne L, Capet C, et al. Clinical presentation of hypernatremia in elderly patients: a case control study. J Am Geriatr Soc. Aug 2006. 54(8):1225-30. [QxMD MEDLINE Link].
Fried LF, Palevsky PM. Hyponatremia and hypernatremia. Med Clin North Am. 1997 May. 81(3):585-609. [QxMD MEDLINE Link].
Chauhan K, Pattharanitima P, Patel N, Duffy A, Saha A, Chaudhary K, et al. Rate of Correction of Hypernatremia and Health Outcomes in Critically Ill Patients. Clin J Am Soc Nephrol. 2019 May 7. 14 (5):656-663. [QxMD MEDLINE Link]. [Full Text].
Sterns RH. Evidence for Managing Hypernatremia: Is It Just Hyponatremia in Reverse?. Clin J Am Soc Nephrol. 2019 May 7. 14 (5):645-647. [QxMD MEDLINE Link]. [Full Text].
Lindner G, Schwarz C, Kneidinger N, et al. Can we really predict the change in serum sodium levels? An analysis of currently proposed formulae in hypernatraemic patients. Nephrol Dial Transplant. 2008 Nov. 23(11):3501-8. [QxMD MEDLINE Link].
Lindner G, Funk GC. Hypernatremia in critically ill patients. J Crit Care. 2012 Jul 2. [QxMD MEDLINE Link].
van IJzendoorn MM, Buter H, Kingma WP, Koopmans M, Navis G, Boerma EC. Hydrochlorothiazide in intensive care unit-acquired hypernatremia: A randomized controlled trial. J Crit Care. 2017 Apr. 38:225-230. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Baldeweg SE, Ball S, Brooke A, Gleeson HK, Levy MJ, Prentice M, et al. SOCIETY FOR ENDOCRINOLOGY CLINICAL GUIDANCE: Inpatient management of cranial diabetes insipidus. Endocr Connect. 2018 Jul. 7 (7):G8-G11. [QxMD MEDLINE Link]. [Full Text].
Lindner G, Schwarz C, Funk GC. Osmotic diuresis due to urea as the cause of hypernatraemia in critically ill patients. Nephrol Dial Transplant. 2012 Mar. 27(3):962-7. [QxMD MEDLINE Link].

Media Gallery

Figure A: Normal cell. Figure B: Cell initially responds to extracellular hypertonicity through passive osmosis of water extracellularly, resulting in cell shrinkage. Figure C: Cell actively responds to extracellular hypertonicity and cell shrinkage in order to limit water loss through transport of organic osmolytes across the cell membrane, as well as through intracellular production of these osmolytes. Figure D: Rapid correction of extracellular hypertonicity results in passive movement of water molecules into the relatively hypertonic intracellular space, causing cellular swelling, damage, and ultimately death.

of 1

Author

Ivo Lukitsch, MD Consulting Staff/Faculty, Department of Nephrology, Ochsner Medical Center

Ivo Lukitsch, MD is a member of the following medical societies: American Society of Nephrology, American Society of Transplantation

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc.

Chief Editor

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Anil Kumar Mandal, MD Clinical Professor, Department of Internal Medicine, Division of Nephrology, University of Florida College of Medicine

Anil Kumar Mandal, MD is a member of the following medical societies: American College of Clinical Pharmacology, American College of Physicians, American Society of Nephrology, Central Society for Clinical and Translational Research

Disclosure: Nothing to disclose.

Acknowledgements

Trung Q Pham, MD Consulting Staff, Department of Internal Medicine, Kayenta Health Center

Disclosure: Nothing to disclose.

Characteristics of hypernatremia	Symptoms related to the characteristics of hypernatremia
Cognitive dysfunction and symptoms associated with neuronal cell shrinkage	Lethargy, obtundation, confusion, abnormal speech, irritability, seizures, nystagmus, myoclonic jerks
Dehydration or clinical signs of volume depletion	Orthostatic blood pressure changes, tachycardia, oliguria, dry oral mucosa, abnormal skin turgor, dry axillae,
Other clinical findings	Weight loss, generalized weakness

Hypernatremia Medication

Medication Summary

Diuretics

Class Summary

Hydrochlorothiazide (Esidrix, HydroDiuril, Microzide)

Hydrochlorothiazide (Esidrix, HydroDiuril, Microzide)

Furosemide (Lasix)

Furosemide (Lasix)

Vasopressin analogs

Class Summary

Desmopressin (DDAVP)

Desmopressin (DDAVP)

Hypernatremia Medication

Medication Summary

Diuretics

Class Summary

Hydrochlorothiazide (Esidrix, HydroDiuril, Microzide)

Hydrochlorothiazide (Esidrix, HydroDiuril, Microzide)

Furosemide (Lasix)

Furosemide (Lasix)

Vasopressin analogs

Class Summary

Desmopressin (DDAVP)

Desmopressin (DDAVP)

References

Tables

Contributor Information and Disclosures

What would you like to print?