Skip to main content
Top
Published in: International Journal of Bipolar Disorders 1/2015

Open Access 01-12-2015 | Review

Lithium nephrotoxicity

Authors: Abed N. Azab, Alla Shnaider, Yamima Osher, Dana Wang, Yuly Bersudsky, R. H. Belmaker

Published in: International Journal of Bipolar Disorders | Issue 1/2015

Login to get access

Abstract

Reports of toxic effects on the kidney of lithium treatment emerged very soon after lithium therapy was introduced. Lithium-induced nephrogenic diabetes insipidus is usually self-limiting or not clinically dangerous. Some reports of irreversible chronic kidney disease and renal failure were difficult to attribute to lithium treatment since chronic kidney disease and renal failure exist in the population at large. In recent years, large-scale epidemiological studies have convincingly shown that lithium treatment elevates the risk of chronic kidney disease and renal failure. Most patients do not experience renal side effects. The most common side effect of polyuria only weakly predicts increasing creatinine or reduced kidney function. Among those patients who do experience decrease in creatinine clearance, some may require continuation of lithium treatment even as their creatinine increases. Other patients may be able to switch to a different mood stabilizer medication, but kidney function may continue to deteriorate even after lithium cessation. Most, but not all, evidence today recommends using a lower lithium plasma level target for long-term maintenance and thereby reducing risks of severe nephrotoxicity.
Literature
go back to reference Aiff H, Attman PO, Aurell M, Bendz H, Schon S, Svedlund J. The impact of modern treatment principles may have eliminated lithium-induced renal failure. J Psychopharmacol. 2014a;28:151–4.PubMedCrossRef Aiff H, Attman PO, Aurell M, Bendz H, Schon S, Svedlund J. The impact of modern treatment principles may have eliminated lithium-induced renal failure. J Psychopharmacol. 2014a;28:151–4.PubMedCrossRef
go back to reference Aiff H, Attman PO, Aurell M, Bendz H, Schon S, Svedlund J. End-stage renal disease associated with prophylactic lithium treatment. Eur Neuropsychopharmacol. 2014b;24:540–4.PubMedCrossRef Aiff H, Attman PO, Aurell M, Bendz H, Schon S, Svedlund J. End-stage renal disease associated with prophylactic lithium treatment. Eur Neuropsychopharmacol. 2014b;24:540–4.PubMedCrossRef
go back to reference American National Kidney Foundation. Clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis. 2002;39:S1–S266. American National Kidney Foundation. Clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis. 2002;39:S1–S266.
go back to reference Angrist BM, Gershon S, Levitan SJ, Blumberg AG. Lithium-induced diabetes insipidus-like syndrome. Compr Psychiatry. 1970;11(2):141–6.PubMedCrossRef Angrist BM, Gershon S, Levitan SJ, Blumberg AG. Lithium-induced diabetes insipidus-like syndrome. Compr Psychiatry. 1970;11(2):141–6.PubMedCrossRef
go back to reference Aprhamian I, Santos FS, dos Santod B, Talib L, Diniz BS, Radanovic M, et al. Long-term, low-dose lithium treatment does not impair renal function in the elderly: a 2-year randomized placebo-controlled trial followed by a single-blind extension. J Clin Psychiatry. 2014;7:e672–8.CrossRef Aprhamian I, Santos FS, dos Santod B, Talib L, Diniz BS, Radanovic M, et al. Long-term, low-dose lithium treatment does not impair renal function in the elderly: a 2-year randomized placebo-controlled trial followed by a single-blind extension. J Clin Psychiatry. 2014;7:e672–8.CrossRef
go back to reference Baylis PH, Heath DA. Water disturbances in patients treated with oral lithium carbonate. Ann Intern Med. 1978;88(5):607–9.PubMedCrossRef Baylis PH, Heath DA. Water disturbances in patients treated with oral lithium carbonate. Ann Intern Med. 1978;88(5):607–9.PubMedCrossRef
go back to reference Bedford JJ, Leader JP, Jing R, Walker LJ, Klein JD, Sands JM, et al. Amiloride restores renal medullary osmolytes in lithium-induced nephrogenic diabetes insipidus. Am J Physiol Renal Physiol. 2008;294(4):F812–20.PubMedCrossRef Bedford JJ, Leader JP, Jing R, Walker LJ, Klein JD, Sands JM, et al. Amiloride restores renal medullary osmolytes in lithium-induced nephrogenic diabetes insipidus. Am J Physiol Renal Physiol. 2008;294(4):F812–20.PubMedCrossRef
go back to reference Bendz H, Andersch S, Aurell M. Kidney function in an unselected lithium population. A cross-sectional study. Acta Psychiatr Scand. 1983;68(5):325–34.PubMedCrossRef Bendz H, Andersch S, Aurell M. Kidney function in an unselected lithium population. A cross-sectional study. Acta Psychiatr Scand. 1983;68(5):325–34.PubMedCrossRef
go back to reference Bendz H, Aurell M, Balldin J, Mathe AA, Sjodin I. Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium. Nephrol Dial Transplant. 1994;9(9):1250–4.PubMed Bendz H, Aurell M, Balldin J, Mathe AA, Sjodin I. Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium. Nephrol Dial Transplant. 1994;9(9):1250–4.PubMed
go back to reference Bendz H, Aurell M, Lanke J. A historical cohort study of kidney damage in long-term lithium patients: continued surveillance needed. Eur Psychiatry. 2001;16(4):199–206.PubMedCrossRef Bendz H, Aurell M, Lanke J. A historical cohort study of kidney damage in long-term lithium patients: continued surveillance needed. Eur Psychiatry. 2001;16(4):199–206.PubMedCrossRef
go back to reference Bendz H, Schon S, Attman PO, Aurell M. Renal failure occurs in chronic lithium treatment but is uncommon. Kidney Int. 2010;77:219–24.PubMedCrossRef Bendz H, Schon S, Attman PO, Aurell M. Renal failure occurs in chronic lithium treatment but is uncommon. Kidney Int. 2010;77:219–24.PubMedCrossRef
go back to reference Boton R, Gaviria M, Batlle DC. Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis. 1987;10(5):329–45.PubMedCrossRef Boton R, Gaviria M, Batlle DC. Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis. 1987;10(5):329–45.PubMedCrossRef
go back to reference Bucht G, Wahlin A. Renal concentrating capacity in long-term lithium treatment and after withdrawal of lithium. Acta Med Scand. 1980;207(4):309–14.PubMed Bucht G, Wahlin A. Renal concentrating capacity in long-term lithium treatment and after withdrawal of lithium. Acta Med Scand. 1980;207(4):309–14.PubMed
go back to reference Close H, Reilly J, Mason JM, Kripalani M, Wilson D, Main J, et al. Renal failure in lithium-treated bipolar disorder: a retrospective cohort study. PLoS One. 2014;9(3):e90169. doi:10.1371.PubMedCentralPubMedCrossRef Close H, Reilly J, Mason JM, Kripalani M, Wilson D, Main J, et al. Renal failure in lithium-treated bipolar disorder: a retrospective cohort study. PLoS One. 2014;9(3):e90169. doi:10.1371.PubMedCentralPubMedCrossRef
go back to reference Coskunol H, Vahip S, Mees ED, Basci A, Bayindir O, Tuglular I. Renal side-effects of long-term lithium treatment. J Affect Disord. 1997;43:5–10.PubMedCrossRef Coskunol H, Vahip S, Mees ED, Basci A, Bayindir O, Tuglular I. Renal side-effects of long-term lithium treatment. J Affect Disord. 1997;43:5–10.PubMedCrossRef
go back to reference Feuerstein G, Zilberman Y, Hemmendinger R, Lichtenberg D. Attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride in rats. Neuropsychobiology. 1981;7(2):67–73.PubMedCrossRef Feuerstein G, Zilberman Y, Hemmendinger R, Lichtenberg D. Attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride in rats. Neuropsychobiology. 1981;7(2):67–73.PubMedCrossRef
go back to reference Gershon S, Chengappa KN, Malhi GS. Lithium specificity in bipolar illness: a classic agent for the classic disorder. Bipolar Disord. 2009;11 Suppl 2:34–44.PubMedCrossRef Gershon S, Chengappa KN, Malhi GS. Lithium specificity in bipolar illness: a classic agent for the classic disorder. Bipolar Disord. 2009;11 Suppl 2:34–44.PubMedCrossRef
go back to reference Hestbech J, Hansen HE, Amdisen A, Olsen S. Chronic renal lesions following long-term treatment with lithium. Kidney Int. 1977;12(3):205–13.PubMedCrossRef Hestbech J, Hansen HE, Amdisen A, Olsen S. Chronic renal lesions following long-term treatment with lithium. Kidney Int. 1977;12(3):205–13.PubMedCrossRef
go back to reference Kallner G, Petterson U. Renal, thyroid and parathyroid function during lithium treatment: laboratory tests in 207 people treated for 1–30 years. Acta Psychiatr Scand. 1995;91(1):48–51.PubMedCrossRef Kallner G, Petterson U. Renal, thyroid and parathyroid function during lithium treatment: laboratory tests in 207 people treated for 1–30 years. Acta Psychiatr Scand. 1995;91(1):48–51.PubMedCrossRef
go back to reference Khairallah W, Fawaz A, Brown EM, El-Hajj FG. Hypercalcemia and diabetes insipidus in a patient previously treated with lithium. Nat Clin Pract Nephrol. 2007;3(7):397–404.PubMedCrossRef Khairallah W, Fawaz A, Brown EM, El-Hajj FG. Hypercalcemia and diabetes insipidus in a patient previously treated with lithium. Nat Clin Pract Nephrol. 2007;3(7):397–404.PubMedCrossRef
go back to reference Kripalani M, Shawcross J, Reilly J, Main J. Lithium and chronic kidney disease. BMJ. 2009;339:b2452.PubMedCrossRef Kripalani M, Shawcross J, Reilly J, Main J. Lithium and chronic kidney disease. BMJ. 2009;339:b2452.PubMedCrossRef
go back to reference Lepkifker E, Sverdlik A, Iancu I, Ziv R, Segev S, Kotler M. Renal insufficiency in long-term lithium treatment. J Clin Psychiatry. 2004;65(6):850–6.PubMedCrossRef Lepkifker E, Sverdlik A, Iancu I, Ziv R, Segev S, Kotler M. Renal insufficiency in long-term lithium treatment. J Clin Psychiatry. 2004;65(6):850–6.PubMedCrossRef
go back to reference Markowitz GS, Radhakrishnan J, Kambham N, Valeri AM, Hines WH, D’Agati VD. Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. J Am Soc Nephrol. 2000;11(8):1439–48.PubMed Markowitz GS, Radhakrishnan J, Kambham N, Valeri AM, Hines WH, D’Agati VD. Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. J Am Soc Nephrol. 2000;11(8):1439–48.PubMed
go back to reference McCann SM, Daly J, Kelly CB. The impact of long-term lithium treatment on renal function in an outpatient population. Ulster Med J. 2008;77(2):102–5.PubMedCentralPubMed McCann SM, Daly J, Kelly CB. The impact of long-term lithium treatment on renal function in an outpatient population. Ulster Med J. 2008;77(2):102–5.PubMedCentralPubMed
go back to reference McKnight RF, Adida M, Budge K, Stockton S, Goodwin FK, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379:721–8.PubMedCrossRef McKnight RF, Adida M, Budge K, Stockton S, Goodwin FK, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379:721–8.PubMedCrossRef
go back to reference Okusa MD, Crystal LJ. Clinical manifestations and management of acute lithium intoxication. Am J Med. 1994;97(4):383–9.PubMedCrossRef Okusa MD, Crystal LJ. Clinical manifestations and management of acute lithium intoxication. Am J Med. 1994;97(4):383–9.PubMedCrossRef
go back to reference Paul R, Minay J, Cardwell C, Fogarty D, Kelly CB. Meta-analysis of the effects of lithium usage on serum creatinine levels. J Psychopharmacol. 2010;24:1425–31.PubMedCrossRef Paul R, Minay J, Cardwell C, Fogarty D, Kelly CB. Meta-analysis of the effects of lithium usage on serum creatinine levels. J Psychopharmacol. 2010;24:1425–31.PubMedCrossRef
go back to reference Paw H, Slingo ME, Tinker M. Late onset nephrogenic diabetes insipidus following cessation of lithium therapy. Anaesth Intensive Care. 2007;35(2):278–80.PubMed Paw H, Slingo ME, Tinker M. Late onset nephrogenic diabetes insipidus following cessation of lithium therapy. Anaesth Intensive Care. 2007;35(2):278–80.PubMed
go back to reference Phillips BD, Gopalakrishnan G, Gohh R, Hennessey JV. Lithium toxicity precipitated by profound hypothyroidism. Thyroid. 2008;18(6):651–4.PubMedCrossRef Phillips BD, Gopalakrishnan G, Gohh R, Hennessey JV. Lithium toxicity precipitated by profound hypothyroidism. Thyroid. 2008;18(6):651–4.PubMedCrossRef
go back to reference Presne C, Fakhouri F, Noel LH, Stengel B, Even C, Kreis H, et al. Lithium-induced nephropathy: rate of progression and prognostic factors. Kidney Int. 2003;64:585–92.PubMedCrossRef Presne C, Fakhouri F, Noel LH, Stengel B, Even C, Kreis H, et al. Lithium-induced nephropathy: rate of progression and prognostic factors. Kidney Int. 2003;64:585–92.PubMedCrossRef
go back to reference Schou M, Vestergaard P. Prospective studies on a lithium cohort. 2. Renal function. Water and electrolyte metabolism. Acta Psychiatr Scand. 1988;78(4):427–33.PubMedCrossRef Schou M, Vestergaard P. Prospective studies on a lithium cohort. 2. Renal function. Water and electrolyte metabolism. Acta Psychiatr Scand. 1988;78(4):427–33.PubMedCrossRef
go back to reference Smigan L, Bucht G, von Knorring L, Perris C, Wahlin A. Long-term lithium treatment and renal functions. A prospective study. Neuropsychobiology. 1984;11(1):33–8.PubMedCrossRef Smigan L, Bucht G, von Knorring L, Perris C, Wahlin A. Long-term lithium treatment and renal functions. A prospective study. Neuropsychobiology. 1984;11(1):33–8.PubMedCrossRef
go back to reference Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol. 1999;10(3):666–74.PubMed Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol. 1999;10(3):666–74.PubMed
go back to reference Toker L, Bersudsky Y, Plaschkes I, Chalifa-Caspi V, Berry G, Moechars D, et al. Inositol related gene knockouts mimic lithiums effect on mitochondrial function. Neuropsychopharmacology. 2014;39:319–28.PubMedCentralPubMedCrossRef Toker L, Bersudsky Y, Plaschkes I, Chalifa-Caspi V, Berry G, Moechars D, et al. Inositol related gene knockouts mimic lithiums effect on mitochondrial function. Neuropsychopharmacology. 2014;39:319–28.PubMedCentralPubMedCrossRef
go back to reference Turan T, Esel E, Tokgoz B, Aslan S, Sofuoglu S, Utas C, et al. Effects of short- and long-term lithium treatment on kidney functioning in patients with bipolar mood disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(3):561–5.PubMedCrossRef Turan T, Esel E, Tokgoz B, Aslan S, Sofuoglu S, Utas C, et al. Effects of short- and long-term lithium treatment on kidney functioning in patients with bipolar mood disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(3):561–5.PubMedCrossRef
go back to reference Vestergaard P, Amdisen A. Lithium treatment and kidney function. A follow-up study of 237 patients in long-term treatment. Acta Psychiatr Scand. 1981;63(4):333–45.PubMedCrossRef Vestergaard P, Amdisen A. Lithium treatment and kidney function. A follow-up study of 237 patients in long-term treatment. Acta Psychiatr Scand. 1981;63(4):333–45.PubMedCrossRef
go back to reference Vestergaard P, Amdisen A, Hansen HE, Schou M. Lithium treatment and kidney function. A survey of 237 patients in long-term treatment. Acta Psychiatr Scand. 1979;60(5):504–20.PubMedCrossRef Vestergaard P, Amdisen A, Hansen HE, Schou M. Lithium treatment and kidney function. A survey of 237 patients in long-term treatment. Acta Psychiatr Scand. 1979;60(5):504–20.PubMedCrossRef
go back to reference Walker RG. Lithium nephrotoxicity. Kidney Int Suppl. 1993;42:S93–8.PubMed Walker RG. Lithium nephrotoxicity. Kidney Int Suppl. 1993;42:S93–8.PubMed
go back to reference Walker RG, Bennett WM, Davies BM, Kincaid-Smith P. Structural and functional effects of long-term lithium therapy. Kidney Int Suppl. 1982;11:S13–9.PubMed Walker RG, Bennett WM, Davies BM, Kincaid-Smith P. Structural and functional effects of long-term lithium therapy. Kidney Int Suppl. 1982;11:S13–9.PubMed
go back to reference Werneke U, Ott M. Response to “The impact of modern treatment principles may have eliminated lithium-induced renal failure” Aiff et al., 2014. J Psychopharmacol. 2014;28:1189–90.PubMedCrossRef Werneke U, Ott M. Response to “The impact of modern treatment principles may have eliminated lithium-induced renal failure” Aiff et al., 2014. J Psychopharmacol. 2014;28:1189–90.PubMedCrossRef
go back to reference Werneke U, Ott M, Renberg ES, Tayler D, Stegmayr B. A decision analysis of long-term lithium treatment and the risk of renal failure. Acta Psychiatr Scand. 2010;126:186–97.CrossRef Werneke U, Ott M, Renberg ES, Tayler D, Stegmayr B. A decision analysis of long-term lithium treatment and the risk of renal failure. Acta Psychiatr Scand. 2010;126:186–97.CrossRef
Metadata
Title
Lithium nephrotoxicity
Authors
Abed N. Azab
Alla Shnaider
Yamima Osher
Dana Wang
Yuly Bersudsky
R. H. Belmaker
Publication date
01-12-2015
Publisher
Springer Berlin Heidelberg
Published in
International Journal of Bipolar Disorders / Issue 1/2015
Electronic ISSN: 2194-7511
DOI
https://doi.org/10.1186/s40345-015-0028-y

Other articles of this Issue 1/2015

International Journal of Bipolar Disorders 1/2015 Go to the issue