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Renal function during long-term lithium treatment: a cross-sectional and longitudinal study.

Bocchetta A, Ardau R, Fanni T, Sardu C, Piras D, Pani A, Del Zompo M - BMC Med (2015)

Bottom Line: The effects of lithium treatment on renal function have been previously shown, albeit with discrepancies regarding their relevance.In the cross-sectional evaluation, eGFR was found to be lower in women (by 3.47 mL/min/1.73 m²), in older patients (0.73 mL/min/1.73 m² per year of age), and in patients with longer lithium treatment (0.73 mL/min/1.73 m² per year).Progression of renal failure throughout the 4-year follow-up after a reduction to an eGFR lower than 45 mL/min/1.73 m² did not differ between the subgroup who continued lithium as before and the subgroup who either discontinued lithium or continued at concentrations below the therapeutic range.

View Article: PubMed Central - PubMed

Affiliation: Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Via Ospedale 54, Cagliari 09124, Italy. bocchett@unica.it.

ABSTRACT

Background: The effects of lithium treatment on renal function have been previously shown, albeit with discrepancies regarding their relevance. In this study, we examined glomerular filtration rate in patients treated with lithium for up to 33 years.

Methods: All lithium patients registered from 1980 to 2012 at a Lithium Clinic were screened. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine concentration using the Modification of Diet in Renal Disease Study Group equation. A cross-sectional evaluation of the last available eGFR of 953 patients was carried out using multivariate regression analysis for gender, current age, and duration of lithium treatment. Survival analysis was subsequently applied to calculate the time on lithium needed to enter the eGFR ranges 45 to 59 mL/min/1.73 m² (G3a) or 30 to 44 mL/min/1.73 m² (G3b). Finally, 4-year follow-up of eGFR was examined in subgroups of patients who, after reduction to an eGFR lower than 45 mL/min/1.73 m² either i) continued lithium at the same therapeutic range or ii) discontinued lithium or continued at concentrations below the therapeutic range (0.5 mmol/L).

Results: In the cross-sectional evaluation, eGFR was found to be lower in women (by 3.47 mL/min/1.73 m²), in older patients (0.73 mL/min/1.73 m² per year of age), and in patients with longer lithium treatment (0.73 mL/min/1.73 m² per year). Half of the patients treated for longer than 20 years had an eGFR lower than 60 mL/min/1.73 m². The median time on lithium taken to enter G3a or G3b was 25 years (95% CI, 23.2-26.9) and 31 years (95% CI, 26.6-35.4), respectively. Progression of renal failure throughout the 4-year follow-up after a reduction to an eGFR lower than 45 mL/min/1.73 m² did not differ between the subgroup who continued lithium as before and the subgroup who either discontinued lithium or continued at concentrations below the therapeutic range.

Conclusions: Duration of lithium treatment is to be added to advancing age as a risk factor for reduced glomerular filtration rate. However, renal dysfunction tends to appear after decades of treatment and to progress slowly and irrespective of lithium continuation.

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Related in: MedlinePlus

Kaplan-Meier curve showing years on lithium treatment taken to enter stage G3b (30 to 44 mL/min/1.73 m2; 68 events out of 953 patients; 1- to 33-year follow-up).
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Fig4: Kaplan-Meier curve showing years on lithium treatment taken to enter stage G3b (30 to 44 mL/min/1.73 m2; 68 events out of 953 patients; 1- to 33-year follow-up).

Mentions: Figures 3 and 4 show the Kaplan-Meier curves regarding the entire sample. Of the 953 patients studied, 136 declined to an eGFR lower than 60 mL/min/1.73 m2 and 68 to an eGFR lower than 45 mL/min/1.73 m2; the median time taken was 25 years (95% confidence interval (CI), 23.2–26.9) and 31 years (95% CI, 26.6–35.4), respectively. The median time taken to decline from range G3a to G3b was 8 years (95% CI, 6.6–9.4).Figure 3


Renal function during long-term lithium treatment: a cross-sectional and longitudinal study.

Bocchetta A, Ardau R, Fanni T, Sardu C, Piras D, Pani A, Del Zompo M - BMC Med (2015)

Kaplan-Meier curve showing years on lithium treatment taken to enter stage G3b (30 to 44 mL/min/1.73 m2; 68 events out of 953 patients; 1- to 33-year follow-up).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4300557&req=5

Fig4: Kaplan-Meier curve showing years on lithium treatment taken to enter stage G3b (30 to 44 mL/min/1.73 m2; 68 events out of 953 patients; 1- to 33-year follow-up).
Mentions: Figures 3 and 4 show the Kaplan-Meier curves regarding the entire sample. Of the 953 patients studied, 136 declined to an eGFR lower than 60 mL/min/1.73 m2 and 68 to an eGFR lower than 45 mL/min/1.73 m2; the median time taken was 25 years (95% confidence interval (CI), 23.2–26.9) and 31 years (95% CI, 26.6–35.4), respectively. The median time taken to decline from range G3a to G3b was 8 years (95% CI, 6.6–9.4).Figure 3

Bottom Line: The effects of lithium treatment on renal function have been previously shown, albeit with discrepancies regarding their relevance.In the cross-sectional evaluation, eGFR was found to be lower in women (by 3.47 mL/min/1.73 m²), in older patients (0.73 mL/min/1.73 m² per year of age), and in patients with longer lithium treatment (0.73 mL/min/1.73 m² per year).Progression of renal failure throughout the 4-year follow-up after a reduction to an eGFR lower than 45 mL/min/1.73 m² did not differ between the subgroup who continued lithium as before and the subgroup who either discontinued lithium or continued at concentrations below the therapeutic range.

View Article: PubMed Central - PubMed

Affiliation: Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Via Ospedale 54, Cagliari 09124, Italy. bocchett@unica.it.

ABSTRACT

Background: The effects of lithium treatment on renal function have been previously shown, albeit with discrepancies regarding their relevance. In this study, we examined glomerular filtration rate in patients treated with lithium for up to 33 years.

Methods: All lithium patients registered from 1980 to 2012 at a Lithium Clinic were screened. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine concentration using the Modification of Diet in Renal Disease Study Group equation. A cross-sectional evaluation of the last available eGFR of 953 patients was carried out using multivariate regression analysis for gender, current age, and duration of lithium treatment. Survival analysis was subsequently applied to calculate the time on lithium needed to enter the eGFR ranges 45 to 59 mL/min/1.73 m² (G3a) or 30 to 44 mL/min/1.73 m² (G3b). Finally, 4-year follow-up of eGFR was examined in subgroups of patients who, after reduction to an eGFR lower than 45 mL/min/1.73 m² either i) continued lithium at the same therapeutic range or ii) discontinued lithium or continued at concentrations below the therapeutic range (0.5 mmol/L).

Results: In the cross-sectional evaluation, eGFR was found to be lower in women (by 3.47 mL/min/1.73 m²), in older patients (0.73 mL/min/1.73 m² per year of age), and in patients with longer lithium treatment (0.73 mL/min/1.73 m² per year). Half of the patients treated for longer than 20 years had an eGFR lower than 60 mL/min/1.73 m². The median time on lithium taken to enter G3a or G3b was 25 years (95% CI, 23.2-26.9) and 31 years (95% CI, 26.6-35.4), respectively. Progression of renal failure throughout the 4-year follow-up after a reduction to an eGFR lower than 45 mL/min/1.73 m² did not differ between the subgroup who continued lithium as before and the subgroup who either discontinued lithium or continued at concentrations below the therapeutic range.

Conclusions: Duration of lithium treatment is to be added to advancing age as a risk factor for reduced glomerular filtration rate. However, renal dysfunction tends to appear after decades of treatment and to progress slowly and irrespective of lithium continuation.

Show MeSH
Related in: MedlinePlus