Polyuria is excessive production of urine–more than 2.5 L/day and even up to 8 L/day. Polyuria may progress to diabetes insipidus. Both polyuria and diabetes insipidus are among the most common side effects of lithium. Polyuria occurs in up to 70% of patients on lithium and diabetes insipidus occurs in between 10 to 20% of patients.
Why are they important?
These conditions are troublesome to the patient, may affect medication adherence, and in rare cases may lead to irreversible tubular dysfunction.
However, active efforts to screen for and manage polyuria/diabetes insipidus are not commonly undertaken.
How lithium causes diabetes insipidus
Normally, antidiuretic hormone (ADH; also known as vasopressin) acts on the distal and collecting tubules of the kidney to reabsorb most of the water that was filtered out into the urine. By increasing or decreasing this reabsorption, the body controls the amount of urine produced.
But, this process may be impaired due to two main reasons: impaired production of ADH by the pituitary (called central diabetes insipidus) or impairment in the kidney’s responsiveness to ADH (called nephrogenic diabetes insipidus).
Lithium impairs the effect of antidiuretic hormone on the distal and collecting tubules. This leads to excessively dilute urine. So, what lithium can cause is nephrogenic diabetes insipidus.
Trivia: The term “Diabetes” means excessive urination which is present in both diabetes mellitus and diabetes insipidus. But diabetes mellitus involves excessive production of urine that is sweet (“mellitus”) while in diabetes insipidus, the urine is bland in taste (“insipid”).
Related Pages
Lithium-induced polyuria and diabetes insipidus: Evaluation
Lithium-induced polyuria and diabetes insipidus: Treatment
References
Allen HM, Jackson RL, Winchester MD, Deck LV, Allon M. Indomethacin in the treatment of lithium-induced nephrogenic diabetes insipidus. Arch Intern Med 1989;149(5):1123-6.
Ball S, McCullough J. Diabetes Insipidus. 2015 Apr 12. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from http://www.ncbi.nlm.nih.gov/books/NBK279011/ PubMed PMID: 25905242.
Batlle DC, von Riotte AB, Gaviria M, Grupp M. Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy. N Engl J Med. 1985;312(7):408-14.
Behl T, Kotwani A, Kaur I, Goel H. Mechanisms of prolonged lithium therapy-induced nephrogenic diabetes insipidus. Eur J Pharmacol. 2015 May 15;755:27-33. PubMed PMID: 25746463.
Bendz H, Aurell M. Drug-induced diabetes insipidus: incidence, prevention and management. Drug Saf. 1999;21(6):449-56.
Bichet DG. Nephrogenic diabetes insipidus. Adv Chronic Kidney Dis. 2006 Apr;13(2):96-104. Review. PubMed PMID: 16580609.
Bockenhauer D, Bichet DG. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol. 2015 Oct;11(10):576-88. PubMed PMID: 26077742.
de Groot T, Sinke AP, Kortenoeven ML, Alsady M, Baumgarten R, Devuyst O, Loffing J, Wetzels JF, Deen PM. Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus. J Am Soc Nephrol. 2016 Jul;27(7):2082-91. PubMed PMID: 26574046; PubMed Central PMCID: PMC4926986.
Devuyst O. Physiopathology and diagnosis of nephrogenic diabetes insipidus. Ann Endocrinol (Paris). 2012 Apr;73(2):128-9. PubMed PMID: 22503803.
Fenske W, Allolio B. Clinical review: Current state and future perspectives in the diagnosis of diabetes insipidus: a clinical review. J Clin Endocrinol Metab. 2012 Oct;97(10):3426-37. PubMed PMID: 22855338.
Finch CK, Kelley KW, Williams RB. Treatment of lithium-induced diabetes insipidus with amiloride. Pharmacotherapy. 2003;23(4):546-50.
Gitlin M. Lithium and the kidney: an updated review. Drug Saf. 1999;20(3):231-43.
Gordon CE, Vantzelfde S, Francis JM. Acetazolamide in Lithium-Induced Nephrogenic Diabetes Insipidus. N Engl J Med. 2016 Nov 17;375(20):2008-2009. PubMed PMID: 27959610.
Khanna A. Acquired nephrogenic diabetes insipidus. Semin Nephrol. 2006 May;26(3):244-8. PubMed PMID: 16713497.
Knoers N. Nephrogenic Diabetes Insipidus. 2000 Feb 12 [updated 2012 Jun 14]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from http://www.ncbi.nlm.nih.gov/books/NBK1177/ PubMed PMID: 20301356.
Kosten TR, Forrest JN. Treatment of severe lithium-induced polyuria with amiloride. Am J Psychiatry. 1986;143(12):1563-8.
Leroy C, Karrouz W, Douillard C, Do Cao C, Cortet C, Wémeau JL, Vantyghem MC. Diabetes insipidus. Ann Endocrinol (Paris). 2013 Dec;74(5-6):496-507. PubMed PMID: 24286605.
Majzoub JA, Srivatsa A. Diabetes insipidus: clinical and basic aspects. Pediatr Endocrinol Rev. 2006 Dec;4 Suppl 1:60-5. PubMed PMID: 17261971.
Makaryus AN, McFarlane SI. Diabetes insipidus: diagnosis and treatment of a complex disease. Cleve Clin J Med. 2006 Jan;73(1):65-71. PubMed PMID: 16444918.
Martin A. Clinical management of lithium-induced polyuria. Hosp Community Psychiatry. 1993;44(5):427-8.
Raedler TJ. Will lithium damage my kidneys? J Psychiatry Neurosci. 2012 May;37(3):E5-6. PubMed PMID: 22515988; PubMed Central PMCID: PMC3341412.
Rej S, Segal M, Low NC, Mucsi I, Holcroft C, Shulman K, Looper K. The McGill Geriatric Lithium-Induced Diabetes Insipidus Clinical Study (McGLIDICS). Can J Psychiatry. 2014 Jun;59(6):327-34. PubMed PMID: 25007407; PubMed Central PMCID: PMC4079152.
Robertson GL. Diabetes insipidus: Differential diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2016 Mar;30(2):205-18. PubMed PMID: 27156759.
Sands JM, Bichet DG; American College of Physicians.; American Physiological Society.. Nephrogenic diabetes insipidus. Ann Intern Med. 2006 Feb 7;144(3):186-94. PubMed PMID: 16461963.
Tredget J, Kirov A, Kirov G. Effects of chronic lithium treatment on renal function. J Affect Disord. 2010 Nov;126(3):436-40. PubMed PMID: 20483164.
Trepiccione F, Christensen BM. Lithium-induced nephrogenic diabetes insipidus: new clinical and experimental findings. J Nephrol. 2010 Nov-Dec;23 Suppl 16:S43-8. PubMed PMID: 21170888.
Copyright © 2017, Rajnish Mago, MD. All rights reserved. May not be reproduced in any form without express written permission.
Disclaimer: The content on this website is provided as general education for medical professionals. It is not intended or recommended for patients or other lay persons or as a substitute for medical advice, diagnosis, or treatment. Patients must always consult a qualified health care professional regarding their diagnosis and treatment. Healthcare professionals should always check this website for the most recently updated information.