The Effect of Serum Lithium Levels on Renal Function in Geriatric Outpatients: A Retrospective Longitudinal Study

Department of Psychiatry, McGill University, Irving Ludmer Research and Training Building, 1033 Pine Avenue West, Montreal, H3A 1A1, Canada, .
Drugs & Aging (Impact Factor: 2.84). 03/2013; 30(6). DOI: 10.1007/s40266-013-0068-x
Source: PubMed


BACKGROUND: Lithium remains an important treatment for bipolar disorder; however, whether elevated lithium levels lead to long-term renal problems is unknown. Previous consensus opinion was that levels should be kept below 0.6 mmol/L in geriatric patients to minimize renal toxicity. OBJECTIVE: We hypothesized that elevated serum lithium levels correlate with decreased renal function [estimated glomerular filtration rate (eGFR)] in geriatric psychiatry outpatients. STUDY DESIGN: This was a 4-year retrospective cohort study (2007-2011). SETTING: We performed this study in three Canadian university-affiliated tertiary care clinics. PATIENTS: Data from 42 lithium-using geriatric psychiatry outpatients was used. INTERVENTION/EXPOSURE: Our main exposure of interest was mean serum lithium level between 2007 and 2011. MAIN OUTCOME MEASURE: Our primary outcome was change in eGFR between 2007 and 2011 (hypothesis formulated before data collection). RESULTS: Lithium levels did not correlate significantly with change in eGFR at 2- or 4-year follow-up (r < 0.12, p > 0.57). There were no significant predictors of change in eGFR in a multiple linear regression model including hypertension, diabetes, baseline eGFR, lithium duration, and lithium levels. CONCLUSION: Lithium levels do not correlate strongly (ρ > 0.5) with decreased eGFR at 2- and 4-year follow-up in geriatric outpatients. These results are not reliably generalizable when treating patients at mean lithium levels greater than 0.8 mEq/L, especially at 4-year follow-up, and larger studies will be necessary to examine the possibility of a smaller correlation. Nonetheless, these data and the existing literature suggest that lithium levels up to 0.8 mmol/L are safe for use in the long-term treatment of geriatric patients with mood disorders without pre-existing chronic renal failure.

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    ABSTRACT: Objectives: Chronic renal failure is very common, affecting 30%-40% of community-dwelling elderly. We wished to verify whether geriatric psychiatry patients are at increased risk of renal dysfunction compared to elderly controls, as well as whether lithium exposure and other factors are important predictors of risk. Method: This is a four-year retrospective cohort and nested case-control study at a Canadian tertiary-care hospital using data from March 2007 to March 2011. We compared 82 geriatric psychiatry outpatients and 200 psychotropic-naïve family medicine controls aged ≥65. Our main continuous measure of renal outcome was change in estimated glomerular filtration rate (eGFR). Multivariate analyses were performed to determine potential risk factors for renal dysfunction in geriatric psychiatry patients, including age, hypertension, diabetes mellitus, diuretics, and lithium duration. Results: Clinically important decreases in eGFR (>8 mL/min/1.73 m(2)) were found in 40.2% of geriatric psychiatry patients compared to 29.5% of controls (p = 0.040). Multivariate analyses found that lithium duration was independently associated with adverse renal outcome in patients with eGFR < 60 mL/min/1.73 m(2). In this sub-population, lithium users had clinically important decreases in eGFR when compared to non-lithium users: 10.3 vs. 0.40 mL/min/1.73 m(2) (p = 0.017). Conclusion: Geriatric psychiatry patients are at a greater risk for clinically important decreases of renal function than similarly aged controls. Lithium appears to be an important risk factor for renal dysfunction when eGFR is <60 mL/min/1.73 m(2). However, in the majority of older adults who have normal kidney function, lithium use appears to be safe.
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    ABSTRACT: Objectives: Little is known about how lithium should be dosed to achieve therapeutic but safe serum concentrations in older adults. In this paper, we investigate how the lithium dose-concentration ratio changes across the lifespan. Methods: This was a cross-sectional analysis of 63 current lithium users aged 20-95 years using data from McGLIDICS (the McGill Geriatric Lithium-Induced Diabetes Insipidus Clinical Study). Participants underwent blood and urine tests, including serum lithium concentrations. Multivariate analyses were conducted to evaluate potential correlates of the lithium dose-concentration ratio. Results: We found that between the ages of 40-95 years, the total daily dose of lithium required to achieve a given serum concentration decreases threefold (500 vs. 1,500 mg for 1.0 mmol/L). Greater age, once-daily dosing, and lower renal function (estimated glomerular filtration rate) were independently associated with a lower lithium dose-concentration ratio. Conclusions: The lithium dose required to achieve a given serum lithium concentration decreases threefold from middle to old age, with this trend continuing into the ninth and tenth decades of life. In order to avoid lithium toxicity in aging patients, continued serum concentration monitoring and judicious dose reduction may be required, particularly in those patients with reduced renal function.
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    ABSTRACT: Objective: Lithium is an important treatment for mood disorders, but concern about its association with renal disease has contributed to its limited use, particularly in older adults. Because high-quality evidence examining renal disease in this population is lacking, this study aims to quantify the prevalence and identify clinical correlates of renal disease in geriatric lithium users. Methods: In a population-based cross-sectional study on 2,480 lithium users aged 70 or more years, the authors searched the provincial administrative health data from Ontario, Canada between April 1, 2005 and March 31, 2011. Prevalence of chronic kidney disease (CKD), acute kidney injury (AKI), and nephrogenic diabetes insipidus (NDI) was measured using International Classification of Diseases, Tenth Revision codes. Logistic regression analyses were used to identify independent correlates of renal disease. Results: The 6-year prevalence rates of CKD, AKI, and NDI were 13.9%, 1.3%, and 3.0%, respectively. Hypertension (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.50-2.79), diabetes mellitus (OR: 1.86; 95% CI: 1.45-2.38), ischemic heart disease (OR: 1.65; 95% CI: 1.24-2.20), NDI (OR: 2.54; 95% CI: 1.47-4.40), AKI (OR: 11.7; 95% CI: 5.26-26.1), lithium use for more than 2 years (OR: 1.71; 95% CI: 1.05-2.81), loop diuretic use (OR: 1.74; 95% CI: 1.26-2.41), hydrochlorothiazide use (OR: 1.48; 95% CI: 1.07-2.05), and atypical antipsychotic use (OR: 1.49; 95% CI: 1.17-1.89) were all independently associated with CKD. Conclusion: Older lithium users have high rates of CKD. Lithium use duration was independently associated with CKD. Longitudinal studies including individuals without lithium exposure will be necessary to confirm whether lithium is indeed a risk factor for CKD in older adults.
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