Long-term lithium therapy and risk of chronic kidney disease, hyperparathyroidism and hypercalcemia: a cohort study

Abstract

Background Lithium is well recognized as the first-line maintenance treatment for bipolar disorder (BD). However, besides therapeutic benefits attributed to lithium therapy, the associated side effects including endocrinological and renal disorders constitute important parameters in prescribing patterns and patient adherence. The objectives of this study is to (i) determine whether long-term lithium therapy is associated with a decrease in renal function, hyperparathyroidism and hypercalcemia and (ii) identify risk factors for lithium-induced chronic kidney disease (CKD). Methods We conducted a single-centered cohort study of adult patients (≥ 18 years) treated with lithium, who were enrolled at Rennes University Hospital in France between January 1, 2018 and June 1, 2020. Required data were collected from the patient’s medical records: demographics characteristics (age, sex, body mass index), biologic parameters (GFR, lithium blood level, PTH and calcium), medical comorbidities (hypertension and diabetes), lithium treatment duration and dosage, and length of hospitalization. Results A total of 248 patients were included (mean age: 60.2 ± 16.5 years). Duration of lithium treatment correlated with (i) deterioration of renal function estimated at − 2.9 mL/min/year (p < 0.0001) and (ii) the development of hyperparathyroidism (p < 0.01) and hypercalcemia (p < 0.01). We also noted that patients with lithium blood level > 0.8 mEq/mL had significantly lower GFR than patients with lithium blood level < 0.8 mEq/mL (61.8 mL/min versus 77.6 mL/min, respectively, p = 0.0134). Neither diabetes mellitus nor hypertension was associated with more rapid deterioration of renal function. Conclusion This study suggests that the duration of lithium treatment contribute to the deterioration of renal function, raising the question of reducing dosages in patients with a GFR < 60 mL/min. Overdoses has been identified as a risk factor for CKD, emphasizing the importance of regular re-evaluation of the lithium dose regimen. Also, long-term lithium therapy was associated with hyperparathyroidism and hypercalcemia. Particular vigilance is required on these points in order to limit the occurrence of endocrinological and renal lithium adverse effects.

Molecular mechanisms and therapeutic potential of lithium in Alzheimer’s disease: repurposing an old class of drugs

“…This toxicity usually reversible by dose reduction or discontinuation of treatment ( Guilliot et al, 2023 ). However, prolonged high-dose lithium therapy can cause damage to the thyroid, parathyroid glands, and kidneys ( Boivin et al, 2023 ). Figure 4 summarizes a summary of the potential side effects, organ damage, and management strategies associated with lithium therapy.…”

“…Long-term lithium treatment may increase the risk of chronic kidney disease, hyperthyroidism, hyperparathyroidism, and hypercalcemia ( Czarnywojtek et al, 2020 ; Boivin et al, 2023 ). The risk associated with long-term lithium therapy may be twice that of non-lithium treatments and may increase with the duration of treatment ( Van Alphen et al, 2021 ; Schoretsanitis et al, 2022 ).…”

“…Therefore, it is necessary to monitor serum creatinine and estimated glomerular filtration rate (eGFR) at intervals of 6 months to 1 year during lithium therapy ( Gitlin, 1993 ). Reduced lithium dose is recommended in patients with eGFR <60 mL/min ( Boivin et al, 2023 ). Lithium has the potential to cause conditions such as goiter, hypothyroidism, or hyperthyroidism.…”

Surgical strategy in lithium‐associated hyperparathyroidism: A population‐based study

“…3 The risk of LAH depends on the duration of lithium exposition; however, on occasion, pre-existing subclinical primary hyperparathyroidism (PHPT) may be revealed by initiating lithium treatment. 3,8 Bipolar disorder per se has not been associated with hypercalcemia. 3,6 The presentation of LAH may differ from that of sporadic PHPT.…”

“…Inactivation of the calcium‐sensing receptor and interference with intracellular second messenger signaling are suggested to be underlying factors for LAH 3 . The risk of LAH depends on the duration of lithium exposition; however, on occasion, pre‐existing subclinical primary hyperparathyroidism (PHPT) may be revealed by initiating lithium treatment 3,8 . Bipolar disorder per se has not been associated with hypercalcemia 3,6 …”