Stratifying Risk for Renal Insufficiency Among Lithium-Treated Patients: An Electronic Health Record Study

Although lithium preparations remain first-line treatment for bipolar disorder, risk for development of renal insufficiency may discourage their use. Estimating such risk could allow more informed decisions and facilitate development of prevention strategies. We utilized electronic health records from a large New England health-care system between 2006 and 2013 to identify patients aged 18 years or older with a lithium prescription. Renal insufficiency was identified using the presence of renal failure by ICD9 code or laboratory-confirmed glomerular filtration rate below 60 ml/min. Logistic regression was used to build a predictive model in a random two-thirds of the cohort, which was tested in the remaining one-third. Risks associated with aspects of pharmacotherapy were also examined in the full cohort. We identified 1445 adult lithium-treated patients with renal insufficiency, matched by risk set sampling 1 : 3 with 4306 lithium-exposed patients without renal insufficiency. In regression models, features associated with risk included older age, female sex, history of smoking, history of hypertension, overall burden of medical comorbidity, and diagnosis of schizophrenia or schizoaffective disorder (p<0.01 for all contrasts). The model yielded an area under the ROC curve exceeding 0.81 in an independent testing set, with 74% of renal insufficiency cases among the top two risk quintiles. Use of lithium more than once daily, lithium levels greater than 0.6 mEq/l, and use of first-generation antipsychotics were independently associated with risk. These results suggest the possibility of stratifying risk for renal failure among lithium-treated patients. Once-daily lithium dosing and maintaining lower lithium levels where possible may represent strategies for reducing risk.