Lithium therapy may be linked with AKI, poor kidney outcomes vs. valproate
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Key takeaways:
- Absolute 10-year CKD risks were similar in both the lithium and valproate groups.
- Of more than 35,000 routine lithium tests, 3% had toxic-range results.
Use of lithium vs. valproate as a prophylactic treatment may be associated with adverse kidney outcomes, including AKI, according to recently published research.
A team led by Alessandro Bosi, MSc, of the department of medical epidemiology and biostatistics at the Karolinska Institutet in Sweden, studied the association between cumulative lithium use for bipolar disorder, elevated lithium levels and kidney outcomes to “quantify absolute and relative risks of chronic kidney disease (CKD) and AKI.”
Absolute 10-year CKD risks were similar in both the lithium and valproate groups. Image: Adobe Stock.
Lithium is the “most effective prophylactic treatment for bipolar disorder and augments the effects of other drugs in treatment-resistant depression,” according to the researchers. But its use is “constrained by concern over its nephrotoxic effects.”
The study examined data from the Stockholm Creatinine Measurements database, a health care use cohort of all adult Stockholm residents, and included 10,946 patients who began lithium or valproate therapy from January 2007 to December 2018. Researchers used an active-comparator design and inverse probability of treatment weights to limit confounding. Main outcomes were CKD progression, AKI, albuminuria and eGFR decrease.
Patients who started lithium therapy were younger, more likely to be female and had a higher prevalence of bipolar disorder, depression and anxiety than in those who started valproate, the study found. During follow-up, there were 421 CKD progression events and 770 AKI events. Results showed that patients who received lithium did not have an increased risk for CKD or AKI vs. those who received valproate. The absolute 10-year CKD risks were similar in both groups, at 8.4% for lithium and 8.2% for valproate. The findings also indicated no difference in the risk of developing albuminuria or the annual rate of eGFR decrease between the two groups. However, high levels of lithium, defined as greater than 1 mmol/L, were associated with increased risk of CKD progression and AKI. Of more than 35,000 routine lithium tests, 3% had toxic-range results.
“[N]ew use of lithium was meaningfully associated with adverse kidney outcomes, with low absolute risks that did not differ between therapies,” Bosi and colleagues wrote. “However, elevated serum lithium levels were associated with future kidney risks, particularly AKI, emphasizing the need for close monitoring and lithium dose adjustment. Further work is needed to understand how to manage those few patients who experience progression or new-onset CKD.”
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