Earlier this year we described a 2015 study by Harald Aiff and colleagues that suggested that long-term lithium use was associated with a risk of kidney failure. That study, published in the Journal of Psychopharmacology, included 630 patients who had taken lithium for at least 10 years. One-third of these patients had evidence of kidney dysfunction, and in 5%, the impairment was severe. Two new studies provide some data that suggest these risks may not be lithium-specific and are comparable to risks that come with taking other medications.
The first, by Stefan Clos et al. in The Lancet Psychiatry, included 1,120 patients followed for up to 12 years. On average, these patients had been exposed to lithium for a little over 4.5 years. Clos and colleagues determined patients’ estimated glomerular filtration rate (eGFR), a measure of how well the blood is filtered by the kidneys. The researchers concluded that there was “no effect of stable lithium maintenance therapy on the rate of change of eGFR over time” compared to other drugs such as quetiapine, olanzapine, or valproate.
The second new study, by Lars Vedel Kessing and colleagues in the journal JAMA Psychiatry, included 26,731 patients exposed to lithium and 420,959 exposed to anticonvulsants. Kessing and colleagues concluded that both exposure to lithium and exposure to an anticonvulsant were associated with an increased rate of chronic kidney disease, but lithium was not associated with end-stage kidney disease (the kind that requires dialysis or renal transplantation).
The three studies taken together suggest the following: Taking lithium for an average of 4–5 years does not affect kidney functioning, and longer exposure may not harm kidney function any more than other medications (such as anticonvulsants) would. However, kidney functioning (in terms of eGFR) does decline with age, and is also lower among those with higher baseline eGRF, those with other illnesses, those taking other drugs that affect the kidneys, and those who experience an episode of lithium toxicity. Read more
Long-term lithium use has long been associated with decreased renal function. But some Swedish researchers noticed that most long-term studies of patients with renal failure had begun in the 1960s and 1970s. In the 1980s, when it became clear that lithium could reduce renal function, doctors began to institute new safety measures for lithium users, including monitoring of blood levels of the drug and of creatinine, a substance that is excreted by the kidneys as part of normal muscle metabolism. So the researchers undertook a new study to examine whether the protocols instituted in the 1980s had reduced the renal risks of long-term lithium use. Unfortunately, they found that some reduced renal function is still common among people who use lithium for longer than 10 years, and this risk does not necessarily decrease when patients stop taking lithium.
The researchers, led by Harald Aiff, published the study in the Journal of Psychopharmacology in 2015. They identified 4,879 patients who had been prescribed lithium, and narrowed this list down to 630 adult patients who had taken lithium for at least 10 cumulative years, who had normal levels of creatinine when they began taking lithium, and on whom good data existed. About one-third of these patients had evidence of chronic renal impairment, and in 5% of these the impairment was severe or very severe.
Aiff and colleagues’ findings show that lithium treatment requires careful monitoring, especially over the long term. Patients must consider the risk/benefit ratio of lithium treatment. Since prevention of mood episodes can preserve an average ten years of life expectancy, and lithium has the best data for efficacy in preventing manic and depressive episodes, patients must weigh the risks of insufficiently treated bipolar illness against the possibility for long-term decreases in kidney function.