eMedicine Specialties > Nephrology > Drug- and Nephrotoxin-Associated Kidney Disorders

Lithium Nephropathy: Follow-up

Author: Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Coauthor(s): Clifford C Dacso, MD, MPH, MBA, John S Dunn Sr Research Chair, The Methodist Hospital Research Institute; Distinguished Research Professor, University of Houston; Mark DT Tran, MD, Staff Physician, Department of Internal Medicine, Baylor College of Medicine
Contributor Information and Disclosures

Updated: Aug 8, 2009

Follow-up

Further Inpatient Care

  • Patients with severe cases of volume depletion with associated electrolyte abnormalities (ie, hypernatremia) may require ICU care.
  • Once aggressive diuresis is initiated or dialysis is performed for acute toxicity, lithium levels should be sequentially checked to ensure that rebound toxic levels and/or delayed gastrointestinal absorption leading to recurrent toxicity do not occur.

Further Outpatient Care

  • Some reports recommend testing the patient's renal-concentrating ability, 24-hour urinary volume, and creatinine clearance before initiating lithium therapy and at 1-year intervals.
  • Schou recommends regular measurements of serum lithium and creatinine every 2-6 months and obtaining serum thyroid-stimulating hormone determinations once a year.

Inpatient & Outpatient Medications

Deterrence/Prevention

  • Lithium has a low therapeutic index; monitor levels closely to prevent acute lithium intoxication.

Complications

  • Some reports have linked acute renal failure to lithium intoxication. In these cases, however, researchers did not exclude decreased perfusion and other causes of volume depletion as possible contributing factors. Nevertheless, physicians must remember that lithium intoxication can cause volume depletion and vice versa.

Prognosis

  • Patients with urine-concentrating defects from lithium treatment usually take weeks to months to recover following discontinuation of lithium. In rare situations, the problem can persist for years.
  • Acute renal failure associated with lithium toxicity has an excellent prognosis.
  • Chronic renal failure associated with lithium use only uncommonly will completely resolve but generally will not progress if the medication is discontinued and other nephrotoxic agents, such as nonsteroidal anti-inflammatory drugs or hypertension, are minimized.

Miscellaneous

Medicolegal Pitfalls

  • Failure to assess the patient for signs of volume depletion
  • Failure to realize that patients with severe cases of volume depletion with associated electrolyte abnormalities (ie, hypernatremia) may require ICU care
  • Failure to correct electrolyte abnormalities in patients with acute disease
  • Failure to realize that lithium has a low therapeutic index and to monitor levels closely to prevent acute lithium intoxication
 


More on Lithium Nephropathy

Overview: Lithium Nephropathy
Differential Diagnoses & Workup: Lithium Nephropathy
Treatment & Medication: Lithium Nephropathy
Follow-up: Lithium Nephropathy
References
Further Reading
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References

  1. Nielsen J, Kwon TH, Christensen BM, et al. Dysregulation of renal aquaporins and epithelial sodium channel in lithium-induced nephrogenic diabetes insipidus. Semin Nephrol. May 2008;28(3):227-44. [Medline].

  2. Mu J, Johansson M, Hansson GC, et al. Lithium evokes a more pronounced natriuresis when administered orally than when given intravenously to salt-depleted rats. Pflugers Arch. Jul 1999;438(2):159-64. [Medline].

  3. Nielsen J, Kwon TH, Frokiaer J, et al. Lithium-induced NDI in rats is associated with loss of alpha-ENaC regulation by aldosterone in CCD. Am J Physiol Renal Physiol. May 2006;290(5):F1222-33.

  4. Garofeanu CG, Weir M, Rosas-Arellano MP, et al. Causes of reversible nephrogenic diabetes insipidus: a systematic review. Am J Kidney Dis. Apr 2005;45(4):626-37.

  5. Stone KA. Lithium-induced nephrogenic diabetes insipidus. J Am Board Fam Pract. Jan-Feb 1999;12(1):43-7. [Medline].

  6. Thompson CJ, France AJ, Baylis PH. Persistent nephrogenic diabetes insipidus following lithium therapy. Scott Med J. Feb 1997;42(1):16-7.

  7. Rojek A, Nielsen J, Brooks HL, et al. Altered expression of selected genes in kidney of rats with lithium-induced NDI. Am J Physiol Renal Physiol. Jun 2005;288(6):F1276-89.

  8. Walker RJ, Weggery S, Bedford JJ, et al. Lithium-induced reduction in urinary concentrating ability and urinary aquaporin 2 (AQP2) excretion in healthy volunteers. Kidney Int. Jan 2005;67(1):291-4.

  9. Li Y, Shaw S, Kamsteeg EJ, et al. Development of lithium-induced nephrogenic diabetes insipidus is dissociated from adenylyl cyclase activity. J Am Soc Nephrol. Apr 2006;17(4):1063-72. [Medline].

  10. Nielsen J, Hoffert JD, Knepper MA, et al. Proteomic analysis of lithium-induced nephrogenic diabetes insipidus: mechanisms for aquaporin 2 down-regulation and cellular proliferation. Proc Natl Acad Sci U S A. Mar 4 2008;105(9):3634-9. [Medline]. [Full Text].

  11. Marples D, Frokiaer J, Knepper MA, et al. Disordered water channel expression and distribution in acquired nephrogenic diabetes insipidus. Proc Assoc Am Physicians. Sep-Oct 1998;110(5):401-6. [Medline].

  12. Boton R, Gaviria M, Batlle DC. Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis. Nov 1987;10(5):329-45. [Medline].

  13. Gill J, Singh H, Nugent K. Acute lithium intoxication and neuroleptic malignant syndrome. Pharmacotherapy. Jun 2003;23(6):811-5.

  14. Paw H, Slingo ME, Tinker M. Late onset nephrogenic diabetes insipidus following cessation of lithium therapy. Anaesth Intensive Care. Apr 2007;35(2):278-80. [Medline].

  15. Robertson GL. Differential diagnosis of polyuria. Annu Rev Med. 1988;39:425-42. [Medline].

  16. Janowsky DS, Soares J, Hatch JP, et al. Lithium effect on renal glomerular function in individuals with intellectual disability. J Clin Psychopharmacol. Jun 2009;29(3):296-9. [Medline].

  17. Farres MT, Ronco P, Saadoun D. Chronic lithium nephropathy: MR imaging for diagnosis. Radiology. 2003;229:570-4. [Medline]. [Full Text].

  18. Wilting I, Baumgarten R, Movig KL, et al. Urine osmolality, cyclic AMP and aquaporin-2 in urine of patients under lithium treatment in response to water loading followed by vasopressin administration. Eur J Pharmacol. Jul 2 2007;566(1-3):50-7. [Medline].

  19. Bedford JJ, Weggery S, Ellis G, McDonald FJ, Joyce PR, Leader JP, et al. Lithium-induced Nephrogenic Diabetes Insipidus: Renal Effects of Amiloride. Clin J Am Soc Nephrol. 2008;epub ahead of print:[Medline]. [Full Text].

  20. Grünfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol. May 2009;5(5):270-6. [Medline].

  21. Bendz H, Aurell M, Lanke J. A historical cohort study of kidney damage in long-term lithium patients: continued surveillance needed. Eur Psychiatry. Jun 2001;16(4):199-206.

  22. Markowitz GS, Radhakrishnan J, Kambham N, et al. Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. J Am Soc Nephrol. Aug 2000;11(8):1439-48. [Medline].

  23. McIntyre RS, Mancini DA, Parikh S, Kennedy SH. Lithium revisited. Can J Psychiatry. May 2001;46(4):322-7.

  24. No authors listed. Lithium nephropathy [editorial]. Lancet. Sep 22 1979;2(8143):619-20. [Medline].

  25. Presne C, Fakhouri F, Noel LH, et al. Lithium-induced nephropathy: Rate of progression and prognostic factors. Kidney Int. Aug 2003;64(2):585-92.

  26. Schou M. Forty years of lithium treatment. Arch Gen Psychiatry. Jan 1997;54(1):9-13; discussion 14-5. [Medline].

  27. Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol. Mar 1999;10(3):666-74. [Medline].

  28. Turan T, Esel E, Tokgoz B, et al. Effects of short- and long-term lithium treatment on kidney functioning in patients with bipolar mood disorder. Prog Neuropsychopharmacol Biol Psychiatry. Apr 2002;26(3):561-5.

  29. Walker RG. Lithium nephrotoxicity. Kidney Int Suppl. Jul 1993;42:S93-8. [Medline].

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Keywords

lithium nephropathy, diabetes insipidus, insipidus, nephropathy, aquaporin, cyclic AMP, lithium intoxication, nephrogenic diabetes insipidus, aquaporins, lithium nephrotoxicity, adenosine monophosphate, cyclic adenosine monophosphate, distal tubular function, urine-concentrating defects, tubular acidification defect, renal tubular acidosis, renal failure, uric acid calculi, polyuria, nocturia, transient natriuresis, hypokalemia, hypercalcemia, antidiuretic hormone, ADH

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Contributor Information and Disclosures

Author

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, 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, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Clifford C Dacso, MD, MPH, MBA, John S Dunn Sr Research Chair, The Methodist Hospital Research Institute; Distinguished Research Professor, University of Houston
Clifford C Dacso, MD, MPH, MBA is a member of the following medical societies: American College of Physicians, American Medical Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Mark DT Tran, MD, Staff Physician, Department of Internal Medicine, Baylor College of Medicine
Mark DT Tran, MD is a member of the following medical societies: American Academy of Family Physicians
Disclosure: Nothing to disclose.

Medical Editor

Anil Kumar Mandal, MD, Clinical Professor, Department of Internal Medicine, Division of Nephrology, University of Florida School 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, and Central Society for Clinical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

George R Aronoff, MD, Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine
George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

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