Introduction: After 40 years of use of lithium in the treatment of mood disorders, the renal risks associated with the long-term exposure to lithium are better known.
Objective: This review is aimed at summarizing the information available in the literature regarding the impact of lithium on renal structure and function, the prevalence of renal abnormalities, the associated risk-factors and the strategy for their identification and management.
Method: Articles were selected using a Medline search. The keywords were lithium, renal function, kidney, nephrotoxicity, renal insufficiency, side-effects, polyuria, diabetes insipidus and drug monitoring.
Result: A well-recognized adverse effect of lithium exposure is the occurrence of nephrotic diabetes insipidus (NDI) resulting in polyuria and polydipsia, which occurs in 20% of the patients on long-term lithium treatment. This side-effect is linked to a deficit in urine concentrating ability. Its occurrence is associated with the duration of lithium therapy. Although this effect of lithium is initially functional and may disappear if the treatment is rapidly stopped, it may become structural and permanent over time. The decision to stop lithium or to treat the NDI with amiloride is mainly based upon its functional impact.
Discussion: A debate has been ongoing for decades regarding whether or not the long-term use of lithium may cause slowly progressive renal failure. According to the recent literature, progressive renal failure occurs in approximately 20% of the patients on long-term lithium treatment, among whom a few develop severe renal insufficiency due to lithium (possibly in conjunction with other somatic factors) in the form of interstitial nephritis. However, there is an increasing number of reports of patients requiring dialysis after long-term exposure to lithium.
Conclusion: Current recommended strategies for minimising the renal side effects of lithium include: avoiding acute episodes of renal toxicity; monitoring serum lithium concentrations in order to achieve optimal efficacy at the lowest possible concentrations; monitoring serum creatinine levels at least on a yearly basis, with discontinuation of lithium use, discussion with a nephrologist if creatinine clearance decreases below 60 ml/mn; and the possible application of lithium into single daily dose.