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Int J Bipolar Disord. 2017 Dec;5(1):27. doi: 10.1186/s40345-017-0096-2. Epub 2017 Aug 1.

Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters.

Author information

1
Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Ltondo@aol.com.
2
The International Consortium for Mood & Psychotic Disorders Research, MRC 306, McLean Hospital, 115 Mill Street, Belmont, MA, 02478-9106, USA. Ltondo@aol.com.
3
Lucio Bini Mood Disorders Centers, Cagliari and Rome, Italy. Ltondo@aol.com.
4
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
5
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
6
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
7
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
8
Unit of Clinical Pharmacology, Azienda Ospedaliero-Universitaria, Cagliari, Italy.
9
Viarnetto Psychiatric Clinic, Lugano, Switzerland.
10
Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
11
Section of Psychiatry, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy.
12
Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
13
Freie Universität Berlin, Charité Universitäts-Medizin, Berlin, Germany.
14
Department of Experimental and Clinic Medicine, Section of Psychiatry, University of Pisa & Institute of Behavioral Science, Pisa, Italy.
15
Lucio Bini Mood Disorders Centers, Cagliari and Rome, Italy.
16
Department of General Psychology, Clinical Psychology, University of Padua, Padua, Italy.
17
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt-am-Main, Germany.
18
Department of Psychiatry, Charité Universitäs-Medizin, Berlin, Germany.
19
NeSMOS Department, 'Sapienza' University and Lucio Bini Mood Disorders Center, Rome, Italy.
20
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
21
Brandenburg Medical School, Neureppin, Germany.
22
The International Consortium for Mood & Psychotic Disorders Research, MRC 306, McLean Hospital, 115 Mill Street, Belmont, MA, 02478-9106, USA.
23
Department of Psychiatry, Queens University, Kingston, Ontario, Canada.
24
Department of Neuroscience, Palermo University, Buenos Aires, Argentina.

Abstract

BACKGROUND:

Concerns about potential adverse effects of long-term exposure to lithium as a mood-stabilizing treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of lithium dose, serum concentration, and duration of treatment; relative effects of lithium exposure vs. aging; and contributions of sex and other factors all remain unclear.

METHODS:

Accordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with lithium carbonate for 8-48 (mean 18) years and aged 20-89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea-nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling.

RESULTS:

Overall, 29.5% of subjects experienced at least one low value of eGFR (<60 mL/min/1.73 m2), most after ≥15 years of treatment and age > 55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer lithium treatment, lower lithium dose, higher serum lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting lithium at age ≥ 40 years.

LIMITATIONS:

Control data for age-matched subjects not exposed to lithium were lacking.

CONCLUSIONS:

Long-term lithium treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum lithium level, longer lithium treatment, lower initial eGFR, and medical comorbidity, as well as older age.

KEYWORDS:

Blood urea nitrogen; Body-mass index; Creatinine; Glomerular filtration rate; Glucose; Lithium; Staging of renal function; White blood cell count; eGFR

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