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

Abstract

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 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 (beta -0.8 [-1; -0.6] ml/min/1.73m2 GFR decrease for each year of treatment), a higher age (beta -0.4 [-0.6; -0.3] ml/min/1.73m2 for each year of age, p<0.001), albuminuria (beta -3.97 [-6.6;-1.3], p=0.003), hypertension (beta -6.85 [-12.6;-1.1], p=0.02) and hypothyroidism (beta -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.