Determinants of Kidney Function and Accuracy of Kidney Microcysts Detection in Patients Treated With Lithium Salts for Bipolar Disorder

• Published in: Frontiers in pharmacology Vol. 12; p. 784298
• Main Authors: Tabibzadeh, Nahid, Faucon, Anne-Laure, Vidal-Petiot, Emmanuelle, Serrano, Fidéline, Males, Lisa, Fernandez, Pedro, Khalil, Antoine, Rouzet, François, Tardivon, Coralie, Mazer, Nicolas, Dubertret, Caroline, Delavest, Marine, Marlinge, Emeline, Etain, Bruno, Bellivier, Frank, Vrtovsnik, François, Flamant, Martin
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 07.01.2022; Frontiers Media S.A
• Subjects: bipolar disorder; CKD-chronic kidney disease; kidney microcysts; Life Sciences; lithium; nephrotoxicity; Pharmaceutical sciences; Pharmacology; kidney microcysts; lithium; bipolar disorder; CKD-chronic kidney disease; nephrotoxicity
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2021.784298

Objectives: Early kidney damage during lithium treatment in bipolar disorder is still hypothetical. We aimed at identifying the determinants of a decreased measured glomerular filtration rate (mGFR) and the accuracy of kidney MRI imaging in its detection. Methods: In this cross-sectional cohort study, 217 consecutive lithium-treated patients underwent mGFR and kidney MRI with half-Fourier turbo spin-echo and Single-shot with long echo time sequences. Results: Median age was 51 [27–62] years, and median lithium treatment duration was 5 [2–14] years. 52% of patients had a stage 2 CKD. In multivariable analysis, the determinants of a lower mGFR were a longer lithium treatment duration (β −0.8 [−1; −0.6] ml/min/1.73 m 2 GFR decrease for each year of treatment), a higher age (β −0.4 [−0.6; −0.3] ml/min/1.73 m 2 for each year of age, p < 0.001), albuminuria (β −3.97 [−6.6; −1.3], p = 0.003), hypertension (β −6.85 [−12.6; −1.1], p = 0.02) and hypothyroidism (β −7.1 [−11.7; −2.5], p = 0.003). Serum lithium concentration was not associated with mGFR. Renal MRI displayed renal microcyst(s) in 51% of patients, detected as early as 1 year after lithium treatment initiation. mGFR and lithium treatment duration were strongly correlated in patients with microcyst(s) (r = −0.64, p < 0.001), but not in patients with no microcysts (r = −0.24, p = 0.09). The presence of microcysts was associated with the detection of an mGFR <45 ml/min/1.73 m 2 (AUC 0.893, p < 0.001, sensitivity 80%, specificity 81% for a cut-off value of five microcysts). Conclusion: Lithium treatment duration and hypothyroidism strongly impacted mGFR independently of age, especially in patients with microcysts. MRI might help detect early lithium-induced kidney damage and inform preventive strategies.