Mood Stabilizing Drug May Help Treat Acute Kidney Injury

Highlight• A single low dose of lithium given to mice following acute kidney injury promotes kidney repair and accelerates the recovery of kidney function.

Acute kidney injury is one of the most common and serious complications of hospitalized patients.

Newswise — Washington, DC (January 9, 2014) — A mood stabilizer used to treat bipolar affective disorders may also help treat acute kidney injury, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings are significant because there are no effective therapies for AKI.

AKI, an abrupt decline in kidney function, is an increasingly prevalent and potentially serious condition that can arise following trauma, sepsis, major surgery, or exposure to drugs that are toxic to the kidneys. Once the injury develops, patients have few established treatment options besides supportive care. AKI afflicts about 5% of all hospitalized patients and approximately 25% to 30% of patients in intensive care units. AKI is one of the most expensive conditions seen in US hospitals, costing the facilities several billions of dollars each year.

Research has shown that glycogen synthase kinase (GSK) 3β is an enzyme that plays a major role in the development of AKI. Fortunately, GSK3β can be blocked by using inhibitors, including novel small molecule chemical compounds and lithium.

Lithium is an FDA-approved mood stabilizer safely used for the past 50 years to treat bipolar affective disorders, but it carries significant side effects when used long-term. Hui Bao, MD, PhD, Rujun Gong, MD, PhD (Rhode Island Hospital, Brown University School of Medicine), and their colleagues discovered that giving mice a single low dose of lithium following AKI blocks GSK3β in injured kidneys, promotes kidney repair, and accelerates the recovery of kidney function.

“Our work suggests that lithium might represent a novel, pragmatic, and affordable therapy to improve kidney recovery after AKI,” said Dr. Gong.

More pre-clinical studies are warranted to see if targeting GSK3β with lithium can improve long-term kidney health. Also, clinical trials are needed to determine the appropriate dose of lithium to promote kidney recovery following AKI in humans.

In an accompanying editorial, Man Livingston, PhD and Zheng Dong, PhD (Medical College of Georgia at Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center) noted that “this study, by demonstrating the effect of lithium on tubular regeneration and repair in AKI, has significantly extended our knowledge of this drug and may broaden its potential therapeutic applications in kidney diseases.”

Study co-authors include Yan Ge, MS, Zhen Wang, MD, PhD, Shougang Zhuang, MD, PhD, Lance Dworkin, MD, and Ai Peng, MD.

Disclosures: This study was made possible in part by the funding from the US National Institutes of Health grant R01DK092485 and the International Society of Nephrology (ISN) Sister Renal Center Trio Program. Dr. Hui Bao was an ISN fellow and a visiting nephrologist at Brown Medical School from Tongji University in Shanghai, China under the support of the ISN fellowship.

The article, entitled “Delayed Administration of a Single Dose of Lithium Promotes Recovery from AKI,” will appear online at http://jasn.asnjournals.org/ on January 9, 2014.

The editorial, entitled “Lithium in Kidney Diseases: Big Roles for the Smallest Metal,” will appear online at http://jasn.asnjournals.org/ on January 9, 2014.

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