Analysing the effect of lithium cessation on renal function in patients with bipolar disorder

Date of ISAC Approval: 
13/03/2020
Lay Summary: 
Bipolar affective disorder is a severe psychiatric disorder affecting 1-3% of the general population. Management is life-long, and can span decades, as onset typically occurs in adolescence or early adulthood. Lithium is an effective treatment, but is associated with kidney damage. There is a need for further studies to consider the natural course of bipolar disorder, lithium treatment, and kidney health; in particular, there is very little data examining the effect of stopping lithium on subsequent kidney function. We plan to quantitatively answer the following questions using routinely collected clinical data: a) What is the natural course of chronic kidney disease for patients taking lithium? b) Does kidney function decline in relation to duration of lithium use, or its onset/offset? c) Can lost kidney function be recovered after lithium withdrawal? Clinicians and patients require clear information to assess the risks and benefits of continued lithium treatment where kidney damage is present. Our data analyses will contribute to improving care and decision making for patients with bipolar disorder on lithium treatment.
Technical Summary: 
Bipolar affective disorder (bipolar disorder, BD) is a severe psychiatric disorder affecting 1-3% of the general population. Management is life-long as onset typically occurs early in life. Lithium is an effective treatment, but is associated with kidney damage. Approximately 30% of patients taking lithium long-term will be diagnosed with early stage chronic kidney disease (CKD); 2-5% of patients will require dialysis, and 0.5% will experience end-stage renal disease (ESRD) (Mcknight et al., 2012). Nephrologists currently advise patients to discontinue lithium when CKD stage 3 is reached (estimated glomerular filtration rate eGFR < 60 mL/min/1.73m2). Lithium withdrawal studies are few and conflicting as to the extent and reversibility of glomerular kidney damage. Some data suggest that once CKD is established, eGFR further declines irrespective of lithium withdrawal (Bocchetta et al., 2015; Bendz et al., 2010). Case studies (Hajek, Alda, & Grof, 2011; Dehning et al., 2017) suggest withdrawal from lithium can result in unmanaged BD and loss of life from suicide. Switching to another mood stabiliser late in the disease course may not be an effective solution, since drug side effects and renal damage may persist or worsen (Werneke et al., 2012). There is a need for further longitudinal studies to review renal function where patients have withdrawn from lithium treatment. Clinicians and patients require clear information to assess the risks and benefits of continued lithium treatment where renal impairment or failure is present. Analytical plan. We will predict eGFR via classical and Bayesian statistical techniques, estimating the instantaneous effect of taking lithium on eGFR, the change in eGFR velocity attributable to being on lithium, and the effect on eGFR trajectory of lithium cessation (past but not current lithium use). Impact. Our analyses will contribute to improving patient-centred care and decision making for patients with BD on life-long treatment.
Health Outcomes to be Measured: 
Rate of change in eGFR over time for patients and control.
Collaborators: 

Dr Rudolf Cardinal - Chief Investigator - University of Cambridge
Dr Efthalia (Lina) Massou - Collaborator - University of Cambridge
Dr Rudolf Cardinal - Corresponding Applicant - University of Cambridge
Dr Shanquan Chen - Collaborator - University of Cambridge
Dr Soumya Banerjee - Collaborator - University of Cambridge
Dr Thomas Hiemstra - Collaborator - University of Cambridge