Lithium may be effective as a mood stabilizer, but questions often come up about its safety, particularly with regard to kidney or renal effects.
A very large study published in November 2015 in JAMA Psychiatry looked at a huge dataset from Denmark in order to provide us with information about these risks.
The study consisted of records from 1.5 million randomly selected Danish patients and compared those records with the records of all patients who had a first psychiatric inpatient or outpatient contact and were diagnosed with a single manic episode or bipolar disorder between 1994 and 2012 (n=10,591), and all persons exposed to lithium (n=26,731) or an anticonvulsant (420,959) identified on the date of their first prescription between 1995 and 2012.
The main author of the study had this to say when interviewed by Reuters Health –
“The most important finding in our study is that lithium can be used in a safe way, not resulting in end-stage chronic kidney disease,” wrote Dr. Lars Vedel Kessing of the Psychiatric Center Copenhagen.
“Another important first-ever finding is that bipolar disorder per se is associated with chronic kidney disease independently of drug treatment. This is most likely due to the increased cardiovascular comorbidity, and our finding together with other data emphasizes that we should put more clinical attention into diagnosing and treating these comorbidities,” he added.
“The evidence for long-term mood stabilization with lithium is now better than for any other potential mood stabilizer,” Dr. Kessing said. “However, when deciding to start lithium treatment or other maintenance drug treatment, the possible impact of long-term lithium treatment on renal function is the major obstacle for clinicians and patients, causing substantial fear.”
Two intriguing findings from the study were that there was an increased risk of both kinds of kidney disease in people who never received a prescription for lithium (in other words there was some increased risk that was associated with just being bipolar). This was not a trivial increased risk. The results are summarized in the image to the right. 
Another intriguing finding was that anticonvulsant treatment (an alternative to lithium) was associated with an increased risk of end-stage kidney disease.
In summary, lithium is associated with an increased risk of kidney disease, which usually shows up as a slowly increasing creatinine (why we do regular labs in all of our patients). With the monitoring done in Denmark among those treated with lithium, there does not appear to be an increased risk of severe or end-stage renal disease (requiring kidney transplantation or dialysis).
Bipolar disorder itself was associated with a significant increase in kidney disease in those who don’t get lithium treatment.
Overall, Dr. Kessing concluded, “The important clinical message is that with initial and regular monitoring of serum creatinine every three to six months and aiming for a serum lithium level of 0.6-0.8 mmol/L there seems to be no or negligible risk of end-stage chronic kidney disease.”
Dr. Guy M. Goodwin of the University of Oxford and Warneford Hospital in the U.K., who wrote an accompanying editorial, told Reuters Health by email, “We have clarity on one of the important risks of lithium, but we should not be put off using it. Lithium is unique in psychiatry because it has been shown to reduce the risk of suicide in bipolar disorder. Since bipolar patients, as a group, have one of the highest rates of suicide, that means it saves lives. We need to use it properly, fully aware that it can cause adverse effects, but confident we can usually manage them.”
That last point is quite important. The risk of death by suicide in bipolar disorder is higher than the risk of any kind of kidney disease in this study (3-5% versus 1.5 – 2.5%). So the overall effect of lithium on mortality would be estimated to be favorable, especially given the evidence that the kidney disease risk was NOT for end-stage kidney disease.
Another study, which was published in Lancet Psychiatry in 2024, looked at a smaller sample of bipolar patients treated with lithium (2025 patients) and compared this sample to 1100 control patients. The authors of this study criticized Kessing for only looking at the diagnosis of kidney disease, not also looking at changes in creatinine levels.
That said, the authors in this study did not find a significant difference in serum creatinine in the two groups studied. The significant difference they found was in the frequency of a diagnosis of kidney disease. Bearing this in mind, it is hard to see why the larger first study should be seen as flawed because of how it defined kidney disease.
The study had several flaws. Their control group was significantly younger than their lithium exposure group. They did not adjust for the effect of having bipolar disorder nor for the use of other drugs (other mood stabilizers). In the Kessing study, both of those had a significant impact on rates of chronic kidney disease, separate from exposure to lithium.
References
Kessing LV, Gerds TA, Feldt-Rasmussen B, Andersen PK, Licht RW. Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease: A Nationwide Population-Based Study. JAMA Psychiatry. 2015;72(12):1182–1191. doi:10.1001/jamapsychiatry.2015.1834
Gislason G, Indridason OS, Sigurdsson E, Palsson R. Risk of chronic kidney disease in individuals on lithium therapy in Iceland: a nationwide retrospective cohort study. Lancet Psychiatry. 2024 Dec;11(12):1002-1011. doi: 10.1016/S2215-0366(24)00324-9. PMID: 39572104.