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

Nahid Tabibzadeh; Anne-Laure Faucon; Emmanuelle Vidal-Petiot; Fidéline Serrano; Lisa Males; Pedro Fernandez; Antoine Khalil; François Rouzet; Coralie Tardivon; Nicolas Mazer; Caroline Dubertret; Marine Delavest; Emeline Marlinge; Bruno Etain; Frank Bellivier; François Vrtovsnik; Martin Flamant

doi:10.3389/fphar.2021.784298

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

Front Pharmacol. 2022 Jan 7:12:784298. doi: 10.3389/fphar.2021.784298. eCollection 2021.

Authors

Nahid Tabibzadeh^{1

2

3}, Anne-Laure Faucon⁴, Emmanuelle Vidal-Petiot^{1

5

6}, Fidéline Serrano^{5

7

8}, Lisa Males⁹, Pedro Fernandez⁹, Antoine Khalil^{5

9}, François Rouzet^{5

10}, Coralie Tardivon^{5

11

12}, Nicolas Mazer¹³, Caroline Dubertret^{5

13}, Marine Delavest¹⁴, Emeline Marlinge¹⁴, Bruno Etain^{5

14}, Frank Bellivier^{5

14}, François Vrtovsnik^{5

6

15}, Martin Flamant^{1

5

6}

Affiliations

¹ Physiologie Rénale-Explorations Fonctionnelles, FHU APOLLO, Assistance Publique Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris, France.
² Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Laboratoire de Physiologie Rénale et Tubulopathies, F-75006, Paris, France.
³ CNRS ERL 8228-Unité Métabolisme et Physiologie Rénale, F-75006, Paris, France.
⁴ Centre de recherche en Epidémiologie et Santé des Populations, INSERM UMR 1018, Renal and Cardiovascular Epidemiology, Université Paris-Saclay, Paris, France.
⁵ Université de Paris, Paris, France.
⁶ Inserm U1149, Paris, France.
⁷ UF d'Hormonologie, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France.
⁸ Institut Cochin-Inserm, U1016-CNRS, UMR8104, Paris, France.
⁹ Radiologie, Assistance Publique Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris, France.
¹⁰ Médecine Nucléaire, Assistance Publique Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris, France.
¹¹ AP-HP, Hôpital Bichat, Département Epidémiologie Biostatistiques et Recherche Clinique, F-75018, Paris, France.
¹² INSERM, Centre d'Investigations cliniques-Epidémiologie Clinique 1425, Hôpital Bichat, F-75018, Paris, France.
¹³ Psychiatrie, Assistance Publique Hôpitaux de Paris, Hôpital Louis Mourier, Paris, France.
¹⁴ Psychiatrie et Medicine Addictologique, DMU Neurosciences, Assistance Publique Hôpitaux de Paris, GH Saint-Louis-Lariboisiere-Fernand-Widal, Paris, France.
¹⁵ Néphrologie, Assistance Publique Hô pitaux de Paris, Hô pital Bichat-Claude Bernard, Paris, France.

Abstract

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 m² GFR decrease for each year of treatment), a higher age (β -0.4 [-0.6; -0.3] ml/min/1.73 m² 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 m² (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.

Keywords: CKD-chronic kidney disease; bipolar disorder; kidney microcysts; lithium; nephrotoxicity.