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

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.

Figure 1

Last available estimated glomerular filtration rate by current age and duration of lithium treatment in 953 patients.

Figure 2

Prevalence of patients falling into different estimated glomerular filtration rate (eGFR) categories among subgroups exposed to lithium for different times. The last two available eGFR values were used to assign patients to the following eGFR categories: G1, both values higher than 89 mL/min/1.73 m²; G1/G2, one value within G1 and one within G2; G2, both values between 60 and 89 mL/min/1.73 m²; G2/G3a, one value within G2 and one within G3a; G3a, both values between 45 and 59 mL/min/1.73 m²; G3b–G5, both values lower than 44 mL/min/1.73 m².

Figure 3

Kaplan-Meier curve showing years on lithium treatment taken to enter stage G3a (45 to 59 mL/min/1.73 m ² ; 136 events out of 953 patients; 1- to 33-year follow-up).

Figure 4

Kaplan-Meier curve showing years on lithium treatment taken to enter stage G3b (30 to 44 mL/min/1.73 m ² ; 68 events out of 953 patients; 1- to 33-year follow-up).