Acute kidney injury (AKI) is associated with a higher mortality. Some studies have shown that the high mortality of AKI patients is closely related with dysfunction of other organs such as lungs, heart, liver, and nervous system. At present, growing evidence indicates that AKI induces other organs dysfunction by systemic inflammation. Identified pathways include: renal local inflammation; blood uric acid increasing through activation of purine metabolic pathway to amplify the inflammatory response signal resulting in a secondary wave of inflammatory cascade by Toll-like receptors (including release of cytokines, chemokines, and inflammatory and anti-inflammatory factors, etc.); and finally the formation of systemic inflammatory response (taking HMGB1 release into the blood as the representative), which are accompanied by oxidative stress, apoptosis pathway activation, and migration of white blood cells, eventually leading to dysfunction of lungs, heart, liver, and nervous system. This paper has reviewed the latest clinical and experimental studies about AKI and its role in causing injury to distant organs, which will help clinicians to better understand AKI pathophysiological processes leading to the distant organ injury, in order to provide reasonable therapeutic targets for reducing mortality of patients with AKI.