Long‐term lithium therapy and risk of chronic kidney disease in bipolar disorder: A historical cohort study

Pahwa, Mehak; Joseph, Boney; Núñez, Nicolás A.; Jenkins, Gregory D.; Colby, Colin; Kashani, Kianoush; Veldić, Marin; Moore, Katherine M.; Betcher, Hannah K.; Özerdem, Ayşegül; Cuellar-Barboza, Alfredo B.; McElroy, Susan L.; Biernacka, Joanna M.; Frye, Mark A.; Singh, Balwinder

doi:10.1111/bdi.13052

Cited by 19 publications

(32 citation statements)

References 46 publications

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“…Importantly, no tubulo-interstitial damage was detected in either aspirin (only) or aspirin and Litreated rats. Taking into account that long-term Li treatment duration is a risk factor for CKD [30][31][32][33][34][35][36][37][38][39], one possible explanation for the discrepancy between our results and those of Walker et al [148] could be the longer treatment duration in the Walker study (6 weeks vs. 24 weeks, respectively).…”

Section: Discussioncontrasting

confidence: 88%

“…Factors that contribute to the development of NDI are elevated blood Li levels, long treatment duration, and high incidence of Li intoxication episodes [31]. Moreover, an unignorable body of data suggests that long-term use of Li increases the risk of chronic kidney disease (CKD) [30][31][32][33][34][35][36][37][38][39][40]. For example, Rej et al [32] found that Li is independently associated with an almost two-fold increase in CKD risk in elderly adults [32].…”

Section: Introductionmentioning

confidence: 99%

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Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats

et al. 2021

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Despite established efficacy in bipolar disorder patients, lithium (Li) therapy has serious side effects, particularly chronic kidney disease. We examined the safety and behavioral effects of combined chronic low-dose aspirin plus low-dose Li in rats to explore the toxicity and therapeutic potential of this treatment. Rats were fed regular or Li-containing food (0.1% [low-dose, LLD-Li] or 0.2% [standard-dose, STD-Li]) for six weeks. Low-dose aspirin (1 mg/kg) was administered alone or together with Li. Renal function and gastric mucosal integrity were assessed. The effects of the combination treatment were evaluated in depression-like and anxiety-like behavioral models. Co-treatment with aspirin did not alter plasma Li levels. Chronic STD-Li treatment resulted in significant polyuria and polydipsia, elevated blood levels of creatinine and cystatin C, and increased levels of kidney nephrin and podocin—all suggestive of impaired renal function. Aspirin co-treatment significantly damped STD-Li-induced impairments in kidney parameters. There were no gastric ulcers or blood loss in any treatment group. Combined aspirin and LLD-Li resulted in a significant increase in sucrose consumption, and in the time spent in the open arms of an elevated plus-maze compared with the LLD-Li only group, suggestive of antidepressant-like and anxiolytic-like effects, respectively. Thus, we demonstrate that low-dose aspirin mitigated the typical renal side effects of STD-Li dose and enhanced the beneficial behavioral effects of LLD-Li therapy without aggravating its toxicity.

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Section: Discussioncontrasting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats

et al. 2021

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“…The prevalence of CKD development was relatively low in our study population, considering that the prevalence of CKD stage 3 in the general population of Korea was 7.9% in the national survey of 2011–12 and the prevalence of CKD stage 3–4 (6.9%) in the US population (Ji and Kim 2016 ; Murphy et al 2016 ), Previous studies in western environments have also reported higher CKD prevalence of 21–55% in long-term lithium users (Lepkifker et al 2004 ; Bendz et al 2010 ; Tredget et al 2010 ; Aiff et al 2014 ). The relatively lower age and shorter treatment duration in our study might have affected study findings (vs. mean age of 39.3 ± 16.0 years and mean duration on lithium of 3.5 ± 3.5 years in our study) (Pahwa et al 2021 ).…”

Section: Discussionmentioning

confidence: 53%

Estimated glomerular filtration rate in Korean patients exposed to long-term lithium maintenance therapy

Cho

Lee

Baek

et al. 2022

Int J Bipolar Disord

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Background Lithium-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. Methods This 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. Results A 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. Conclusions In 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.

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“…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 3 .…”

mentioning

confidence: 90%

“…For example, Pahwa et al 2 reported that among 154 patients who received long‐term lithium treatment, 41 patients (27%) developed chronic kidney disease (CKD; eGFR of less than 60 ml/min/ 1.73 m 2 ). Type 2 diabetes mellitus and benzodiazepine use were independent predictors for CKD development in the survival analysis after controlling for age.…”

mentioning

confidence: 99%

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

Terao

2022

Bipolar Disorders

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Long‐term lithium therapy and risk of chronic kidney disease in bipolar disorder: A historical cohort study

Cited by 19 publications

References 46 publications

Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats

Safety and Efficacy of Combined Low-Dose Lithium and Low-Dose Aspirin: A Pharmacological and Behavioral Proof-of-Concept Study in Rats

Estimated glomerular filtration rate in Korean patients exposed to long-term lithium maintenance therapy

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

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