Journal Article Annotations
2021, 4th Quarter

Psychonephrology

Annotations by Sahil Munjal, MD
December, 2021

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

PUBLICATION #1 — Psychonephrology

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

Georgios Schoretsanitis, Renato de Filippis, Brian M Brady, Philipp Homan, Trisha Suppes, John M Kane

Abstract: Bipolar Disord. 2021 Nov 16. doi: 10.1111/bdi.13154. Online ahead of print.

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% CI = 19.1-31.3, 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.

Annotation

The finding:
In this systematic review, one-fourth of patients treated with lithium developed CKD Stages 3–5 after a long-term therapy duration (Primary outcome) with a pooled OR of 2.09 compared to the risk of CKD with a treatment other than lithium. In elderly patients, the prevalence of CKD increased up to one-third. The only significant moderator was the duration of lithium treatment with a trend being observed for cardiovascular disease.

Strength and weaknesses:
The review had wide inclusion criteria; nevertheless, majority of studies were rated high/fair using a scale for quality assessment. Sensitivity analyses were re-assuring and add internal validity. There was no evidence of publication bias. Substantial heterogeneity was seen across included studies due to their design. There was a risk of confounding due to polypharmacy of psychiatric/non-psychiatric drugs.

Relevance:
Lithium’s efficacy along with reported anti suicidal properties and neuroprotective effects makes it a mainstay in the treatment of bipolar disorder. Lithium has been consistently associated with significant renal impairment across multiple studies, even as this risk varies somewhat with multiple confounding variables and use of different measures. Though this review shows a twofold increased risk, but there is limited evidence to predict which patients on lithium therapy will develop CKD and thereby progress to ESRD. The study authors do highlight that lithium use should not be discouraged in bipolar patients. However, psychiatrists should regularly monitor renal function in patients with long duration of lithium treatment, especially who are elderly, have cardiovascular disease, and on the verge of developing CKD.