title: Duration of lithium treatment is a risk factor for reduced glomerular function: a cross-sectional study.
abstract: BACKGROUND
  The adverse renal effects of lithium have long been known, but glomerular insufficiency had been considered an unlikely event until recently, when new studies have raised concern regarding very long-term treatment. In this cross-sectional study, we examined glomerular function in a cohort of patients treated with lithium for up to 33 years and a control group of lithium-naïve patients treated with other mood-stabilizers.
  
  
  METHODS
  Patients with a diagnosis of recurrent or persistent affective disorders, examined between 1 October 2007 and 31 December 2009, were screened. Demographic and clinical data were extracted from clinical charts regarding two study groups: one for patients treated with lithium for at least 12 months and the other for patients never exposed to lithium. Multivariate regression analysis was applied: the dependent variable was the estimated glomerular filtration rate (eGFR) calculated from the last available serum creatinine value using the Modification of Diet in Renal Disease Study Group equation; the following independent variables, potentially associated with renal dysfunction, were included: gender, current age, duration of lithium treatment, cigarette smoking, hypertension, diabetes and dyslipidemia.
  
  
  RESULTS
  eGFRs lower than 60 ml/min were significantly more frequent in the group treated with lithium (38/139 = 27.3%) compared to lithium-naïve patients (4/70 = 5.7%) (P = 0.0002; Fisher's test). Regression analysis showed a significant effect on eGFR of age, gender and duration of lithium treatment but no effect of cigarette smoking, hypertension, diabetes or dyslipidemia. eGFR was estimated to decrease by 0.64 ml/min (95% confidence interval = 0.38 to 0.90; P = 0.00) for each year of lithium treatment.
  
  
  CONCLUSIONS
  The duration of lithium treatment is a risk factor for glomerular failure, in addition to advancing age. For example, all patients aged 60 years or older may be estimated to undergo Stage 3 or more severe chronic kidney disease (namely an eGFR less than 60 ml/min) if treated with lithium for 30 years. These data may be added to the current debate on the balance between the protective effects of lithium on recurrent affective disorders and suicide and the risk of renal disease.See related commentary article here http://www.biomedcentral.com/1741-7015/11/34.
authors: Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Via Ospedale 54, Cagliari, 09124 Italy. bocchett@unica.it
authors: Alberto
authors: A
authors: Bocchetta
authors: Raffaella
authors: R
authors: Ardau
authors: Paolo
authors: P
authors: Carta
authors: Franca
authors: F
authors: Ligas
authors: Claudia
authors: C
authors: Sardu
authors: Antonello
authors: A
authors: Pani
authors: Maria
authors: M
authors: Del Zompo
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects*; D008094:Lithium / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011619:Psychotropic Drugs / Q000008:administration & dosage* / Q000009:adverse effects*; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000503:physiopathology; D012307:Risk Factors; D013997:Time Factors
chemical_list: D011619:Psychotropic Drugs; D008094:Lithium; D003404:Creatinine
references: JAMA. 2007 Nov 7;298(17):2038-47
references: 17986697
references: J Clin Psychopharmacol. 2007 Oct;27(5):544-6
references: 17873708
references: J Am Soc Nephrol. 2004 Aug;15(8):2178-85
references: 15284303
references: Bipolar Disord. 2009 Jun;11 Suppl 2:10-9
references: 19538682
references: Ann Intern Med. 1999 Mar 16;130(6):461-70
references: 10075613
references: Acta Pharmacol Toxicol (Copenh). 1958;15(1):70-84
references: 13594513
references: Ann Intern Med. 2012 Jun 5;156(11):785-95, W-270, W-271, W-272, W-273, W-274, W-275, W-276, W-277,
references: 22312131
references: Kidney Int. 1977 Sep;12(3):205-13
references: 926612
references: Gen Hosp Psychiatry. 2010 May-Jun;32(3):341.e3-5
references: 20430244
references: Am J Psychiatry. 2004 Feb;161(2):217-22
references: 14754766
references: Lancet. 2012 Feb 25;379(9817):721-8
references: 22265699
references: Kidney Int. 1981 Nov;20(5):663-70
references: 7343714
references: Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003492
references: 17054174
references: Drugs. 1981 Dec;22(6):461-76
references: 7032874
references: Acta Psychiatr Scand. 1992 Sep;86(3):218-22
references: 1414416
references: Acta Psychiatr Scand. 2012 Sep;126(3):186-97
references: 22404233
references: J Affect Disord. 2010 Nov;126(3):436-40
references: 20483164
references: Kidney Int. 2010 Feb;77(3):219-24
references: 19940841
references: Am J Psychiatry. 2005 Oct;162(10):1805-19
references: 16199826
references: Drug Saf. 1999 Mar;20(3):231-43
references: 10221853