Bipolar Drug May Help to Treat Acute Kidney Injury

While acute kidney injury (AKI) afflicts about 5% of all hospitalized patients and approximately 25% to 30% of patients in the intensive care unit, there are currently no effective treatments for this common and potentially life-threatening complication. Researchers at Brown University have made a discovery that has the potential to change the therapeutic landscape. They found that lithium—a mood stabilizer traditionally used to treat bipolar affective disorders—may also help to treat AKI. Rujun Gong, MD, PhD, and colleagues demonstrated that delayed administration of a single low dose of lithium promotes kidney repair and accelerates recovery in kidney function following AKI in mice. “Our study paves the way for future clinical trials to explore the use of lithium to improve kidney repair and rescue kidney function following AKI in humans,” says Gong, an associate professor of medicine at the Brown University School of Medicine in Providence, R.I. “If confirmed by clinical trials, this lithium-based therapy might represent a novel, pragmatic, and affordable treatment of acute kidney injury and could substantially reduce the heavy burden of mortality and morbidity caused by acute kidney injury.” Due to the lack of widespread use of novel sensitive biomarkers of kidney injury, Gong says the diagnosis of AKI is usually delayed. Patients have already incurred severe kidney damage by the time they are diagnosed, making it very difficult to find an effective treatment to repair and regenerate the damaged kidney tissues. “In the past 30 years, clinical management of AKI has still been largely limited to symptomatic treatments and general supportive measures, including fluid resuscitation and renal replacement therapy,” Gong explains. “These treatments are, however, of limited utility with unsatisfying therapeutic efficacy. Specific therapeutic interventions that either rescue kidney injury or improve survival are still unavailable in clinical practice.” Lithium has a reparative and protective effect because it selectively targets glycogen synthase kinase 3β (GSK3β), a key cell signaling molecule that plays a significant role in the development of AKI. The psychiatric dose of lithium carries significant side effects that predispose patients on long-term chronic lithium maintenance treatment to poisoning; however, the dose used in this study is only one-third to one-half of the psychiatric dose. “In our study, no noticeable side effects were observed in the animals treated with a single low dose of lithium,” Gong says. “Nevertheless, the kidney protective dose of lithium for humans is unknown.” He and his colleagues plan to carry out a pilot clinical trial in patients with AKI to define the optimal dose of lithium in humans that promotes recovery of kidney function. —Colleen Mullarkey Reference Bao H, Ge Y, Wang Z, Zhuang S, Dworkin L, Peng A, Gong R. Delayed administration of a single dose of lithium promotes recovery from AKI. J Am Soc Nephrol. Jan 9, 2014. [Epub ahead of print.]