Kidney function and long-term treatment with lithium salts for bipolar disorder Determinants of mGFR and accuracy of kidney microcysts detection in the diagnosis of CKD

Background and objectives Kidney damage during early stages of 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. Design, setting, participants and measurements Cross sectional cohort study. Systematic evaluation including mGFR of 217 consecutive adult patients treated with lithium carbonate. Kidney MRI imaging in 99 patients with half-Fourier turbo spinecho 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/1.73m2 GFR decrease for each year of treatment), a higher age (β −0.4 [-0.6; −0.3] ml/min/1.73m2 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. Patients with mGFR<60 ml/min/1.73m2 (22%) had a higher prevalence and number of renal microcysts. Renal MRI displayed renal microcyst(s) in 51% of patients, detected as early as one 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/1.73m2 (AUC 0.893, p<0.001, sensitivity 80%, specificity 81% for a cut-off value of 5 microcysts). Conclusions Besides usual risk factors of GFR decrease, lithium treatment duration strongly impacted mGFR independently of age, especially in patients with microcysts. Hypothyroidism was also negatively associated with kidney function in these patients. MRI might help detect early lithium-induced kidney damage and inform preventive strategies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was performed according to the Declaration of Helsinki. The study was submitted to and approved by the local ethics committee from APHP.Nord (Institutional Review Board CER-2021-74). All patients provided written informed consent before inclusion in the study cohort. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data are available upon reasonable request to the corresponding author.