MedicalResearch.com Interview with:
Dr. Stefan Clos MSc Applied Health Statistics
Murray Royal Hospital
Medical Research: What is the background for this study?
Dr. Clos: For more than 40 years there has been a debate about the long-term effect of lithium maintenance therapy on renal function. There is a lack of good quality data from randomized clinical trials and two previous meta-analyses from 2010 and 2012 suggest that little evidence exists for a clinically significant reduction in renal function in most patients who are on lithium therapy. However, the two publications point out the poor quality of available study data, emphasising the need for large scale epidemiological studies that control for confounders. Several population-based studies have since attempted to address this problem, but had insufficient ability to adjust for confounders or had limitations because of inappropriate cross-sectional study design or did not include an appropriate comparator group.
Medical Research: What are the main findings?
Dr. Clos: This study is the first population-based study in patients with incident lithium exposure that was able to adjust for co-morbidities, co-prescribed medication, and episodes of lithium toxicity in a longitudinal design. We included patients with incidence exposure to Lithium or other first line drugs (Quetiapine, Olanzapine, and Semisodium Valproate), linking laboratory and prescribing data from the Health Informatics Centre at the University of Dundee, Scotland UK. Maximum follow-up was 12 years. Primary outcome was the estimated Glomerular Filtration Rate (eGFR).
Statistical Modelling identified significant predictors for eGFR decline as age, baseline eGFR, co- morbidities, co-prescriptions of nephrotoxic drugs and episodes of Lithium toxicity, but not exposure length or mean lithium serum level.
Mean (age, sex and baseline eGFR) adjusted annual eGFR in the Lithium group was 1.3 ml/min (SE 0.2 ml/min), which was non-significantly more than the comparator group. After adjusting for additional confounders from above we estimate the annual decline for the Lithium group as 1.0 ml/min (SE 0.2 ml/min), again non-significantly more than the comparator group.
Our data suggest that stable lithium maintenance therapy does not increase the risk of renal dysfunction in adult patients with affective disorder who have a baseline eGFR higher than 60 mL/min.
Our results therefore contradict the concept that long-term Lithium therapy is associated with nephrotoxicity in the absence of episodes of acute intoxication and that duration of therapy and cumulative dose are the major determinants of toxicity.
Medical Research: What should clinicians and patients take away from your report?
Dr. Clos: The present findings should help to reassure patients starting lithium treatment. Clinicians should take these findings into account when considering discontinuation of lithium maintenance therapy due to assumed chronic nephrotoxicity. In keeping with the 2008 NICE guidelines, the focus for patients (with incidental chronic kidney disease detected at baseline or when long-term lithium users develop chronic kidney disease) should be active management of diabetes, hypertension, and other cardiovascular risk factors, and avoidance of episodes of acute lithium toxicity.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Clos: Our findings need to be replicated in other populations. Future research could focus on patients with eGFR less than 60 mL/min, elderly patients, and patients from different ethnic groups.
Dr. Stefan Clos MSc (2015). Does Lithium Really Cause Kidney Toxicity?