Long term lithium exposure and chronic kidney disease in the elderly with bipolar disorder: a systematic review and meta-analysis

PURPOSE OF REVIEW: Lithium remains the most effective long-term treatment for bipolar disorder, but concern about chronic kidney disease (CKD) continues to limit its use in older adults, in whom renal reserve is already reduced and competing renal risk factors are common. Whether that concern is proportionate, and whether risk depends on serum concentration or on the comparator chosen, remains unsettled. We synthesized the observational evidence on lithium and CKD in adults aged 50 and over with bipolar disorder. RECENT FINDINGS: Across 6 cohorts, lithium was associated with a higher risk of CKD than nonlithium exposure (pooled hazard ratio 1.62, 95% confidence interval 1.25-2.11), although heterogeneity was substantial and the prediction interval crossed the null. Risk tracked with serum concentration: a higher-versus-lower contrast across 5 cohorts gave a pooled hazard ratio of 2.07 (1.47-2.91), the least heterogeneous analysis and the only one whose prediction interval lay entirely above the null. Against valproate the association attenuated to 1.39 (0.77-2.51). Hard kidney-failure endpoints were too few to estimate reliably. No study reported cognition in relation to renal function. No study was at low risk of bias, and confounding was the dominant concern. SUMMARY: In older adults with bipolar disorder, lithium is associated with a modest, concentration-dependent increase in CKD risk that narrows when valproate rather than nonuse is the comparator. The evidence is observational and confounding-prone, and supports minimising serum concentration and monitoring renal function against age-appropriate thresholds rather than avoiding lithium.