Abstract
BackgroundLithium-induced nephrotoxicity has long been debated. However, it has been rarely explored in Asian populations. The aim of the present study was to assess the effect of lithium maintenance therapy on estimated glomerular filtration rate (eGFR) in Korean patients diagnosed with a psychiatric illness.MethodsThis was a single-centered, retrospective study that included patients treated with lithium or comparator drug (valproate) in Samsung Seoul Medical Center between November 1994 and July 2020. Patients diagnosed with ICD codes F20-33 who had ≥ 6 months of exposure to lithium or valproate were included. Patients had to have ≥ 1 baseline and ≥ 2 post-baseline eGFR data with post-baseline data having an interval of at least 30 days. Chronic kidney disease (CKD) was defined as CKD stage 3 (eGFR < 60 mL/min/1.732). To be considered as CKD, the threshold had to be met at two consecutive post-baseline measurements. Those treated with both lithium and valproate, diagnosed with CKD stages 3–5, diagnosed with a renal disease, or received kidney transplantation were excluded.ResultsA total of 766 patients were included (242 treated with lithium and 524 with valproate). Two (0.8%) in the lithium group and 8 (1.5%) in the valproate group developed CKD stage 3. None developed CKD stages 4–5. Median yearly eGFR change was − 1.3 mL/min/1.732 (IQR: − 6.8, 1.7) for the lithium group and − 1.1 mL/min/1.732 (IQR: − 4.5, 1.5) for the valproate group, showing no significant difference between the two groups (p = 0.389). The rate of decline was more rapid for those with CKD in both groups. eGFR values of lithium and valproate groups did not show significant differences during a follow-up duration of 15 years or more. A significant negative correlation between baseline eGFR and yearly eGFR change was identified in a linear regression analysis.ConclusionsIn Korean patients, treatment with lithium did not increase the risk of developing CKD compared to treatment with valproate. Prevalence of CKD was lower than those previously reported in western populations. Low baseline eGFR showed significant correlation with changes in renal function.
Highlights
Other reports have stated that the rate of estimated glomerular filtration rate (eGFR) decline does not significantly differ between long-term lithium users and patients treated with other psychotropic agents, advocating the safety of lithium maintenance therapy (Clos et al 2015)
As patients who are exposed to lithium have a high probability of co-prescription of other psychotropic medication (Baek et al 2014; Fung et al 2019), additional effects of polypharmacy on renal function should be minimized by selecting comparison groups who are likely to be on similar sets of medications
Patients treated with lithium tended to be younger than those treated with valproate
Summary
The effect of long-term lithium treatment on renal function has been the topic of debate. Other reports have stated that the rate of eGFR decline does not significantly differ between long-term lithium users and patients treated with other psychotropic agents, advocating the safety of lithium maintenance therapy (Clos et al 2015). These discrepancies might have derived from differences in study design and comparator groups. Increased risk of renal impairment associated with lithium treatment reported in numerous studies may be a result of overestimation due to surveillance bias (Nielsen et al 2018)
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