Prevalence of impaired kidney function in patients with long‐term lithium treatment: A systematic review and meta‐analysis

Abstract

Objectives: Although lithium renal effects have been extensively investigated, prevalence rates of chronic kidney disease (CKD) in lithium-treated patients vary. Our aim was to provide prevalence estimates and related moderators. Methods:We performed a systematic review in PubMed/Embase until November 01, 2021, conducting a random effects meta-analysis of studies evaluating CKD prevalence rates in lithium-treated patients calculating overall prevalence ±95% confidence intervals (CIs). Meta-regression analyses included sex, age, body mass index, smoking, hypertension, diabetes, cardiovascular disease, lithium-treatment dose, duration, and blood levels. Subgroup analyses included sample size, diagnoses, and study design.Pooled odds ratios (OR) were estimated for studies including patients receiving nonlithium treatment. Study quality was assessed using the Newcastle-Ottawa scale.Results: Five, nine, and six trials were rated as high, fair, and low quality, respectively.In 20 studies (n = 25,907 patients), we estimated an overall prevalence of 25.5% (95% CI = 19.8-32.2) of impaired kidney function; despite lack of differences (p = 0.18), prevalence rates were higher in elderly samples than mixed samples of elderly and nonelderly (35.6%, 95% CI = 21.4-52.9, k = 2, n = 3,161 vs. 25.1%, 95% k = 18, n = 22,746). Prevalence rates were associated with longer lithium treatment duration (p = 0.04). Cross-sectional studies provided lower rates than retrospective studies (14.5%, 95% CI = 13.5-15.5, k = 6, n = 4,758 vs. 29.5%, 95% CI = 22.1-38.0, k = 12, n = 17,988, p < 0.001). Compared with 722,529 patients receiving nonlithium treatment, the OR of impaired kidney function in 14,187 lithium-treated patients was 2.09 (95% CI = 1.24-3.51, k = 8, p = 0.005).Conclusions: One-fourth of patients receiving long-term lithium may develop impaired kidney function, although research suffers from substantial heterogeneity between studies. This risk may be twofold higher compared with nonlithium treatment and may increase for a longer lithium treatment duration.

The importance of comorbidities and concurrent drugs for assessing renal function of lithium treated patients

“…Considering the above findings, not only lithium treatment duration, 3,4 but also type-2 diabetes mellitus, 2 benzodiazepine use, 2 cardiovascular disease, 3 albuminuria, 4 hypertension, 4 hypothyroidism, 4 and microcysts 4 may possibly worsen renal function independently or moderate the risk of impaired renal function induced by lithium. In addition, the debate on the role of episodes of acute lithium toxicity as risk moderators is ongoing.…”

“…In addition, the debate on the role of episodes of acute lithium toxicity as risk moderators is ongoing. 3…”

“…The authors concluded that progression of CKD could be influenced by existing comorbidities and may not necessarily be due to lithium alone. Also, Schoretsanitis et al 3 meta-analyzed 20 studies with a total of 25,907 lithium-treated individuals and estimated a 25.5% prevalence rate of impaired renal function (eGFR <60 ml/ min/1.73 m 2 ). In comparison to control group of patients receiving treatment other than lithium, they estimated a pooled OR of 2.09 for impaired renal function in patients under long-term lithium treatment.…”

Lithium bidirectionally regulates depression- and mania-related brain functional alterations without worsening cognitive function in patients with bipolar disorder

“…Lithium, a well-known mood stabilizer, has long been used to treat mania in patients with bipolar disorder (BP), and as a synergist in the treatment of depression in these patients, especially those who have attempted suicide (1). These applications have been proven to be clinically effective (2)(3)(4)(5), and based on data from many double-blind randomized controlled studies and other research, lithium is the goldstandard maintenance treatment for BP (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). More notably, Rybakowski modified the definition of mood stabilizer: ' A drug that if used as mono-therapy: (1) act therapeutically in mania or/and in depression; (2) acts prophylactically against manic or/and depressive episodes as demonstrated in a trial of at least 1 year's duration and (3) does not worsen any therapeutic or prophylactic aspect of the illness outlined above.'…”

Lithium and the risk of chronic kidney disease: A population‐based case–control study

“…13 A recent meta-analysis of observational studies has suggested that one fourth of the patients treated with lithium may develop moderate or advanced CKD after longterm treatment, with a two-fold increased risk compared with patients receiving treatments other than lithium. 14 Interestingly, lithium might also have an impact on thyroid and parathyroid function as well, potentially increasing the risk of hypothyroidism and raising total plasma calcium concentration. 11 Using the comprehensive high-quality Danish registers, combining prescription information with laboratory data, we aimed to assess the association between use of lithium and the subsequent risk of CKD.…”