Acute kidney injury-associated delirium: a review of clinical and pathophysiological mechanisms

Abstract

Acute kidney injury is a known clinical risk factor for delirium, an acute cognitive dysfunction that is commonly encountered in the critically ill population. In this comprehensive review of clinical and basic research studies, we detail the epidemiology, clinical implications, pathogenesis, and management strategies of patients with acute kidney injury-associated delirium. Specifically addressed are the pathological roles of endogenous toxin or drug accumulation, acute kidney injury-mediated neuroinflammation, and acute kidney injury-associated volume overload as discrete potential biological mechanisms of the condition. The optimization of clinical contributors and normalization of renal function are reviewed as pragmatic management strategies in addition to potential and emerging therapeutic approaches.

Fig. 1

Proposed mechanisms of cognitive dysfunction as a result of acute kidney injury. TLR-4, toll-like receptor-4; KC, keratinocyte-derived chemokine; G-CSF, granulocyte colony-stimulating factor; MCP-1, monocyte chemoattractant protein-1; and GFAP, glial fibrillary acidic protein

Fig. 2

Post-AKI microglial and astrocyte activation as potential cellular drivers of delirium. AKI, acute kidney injury; TNF, tumor necrosis factor; IL, interleukin; and BBB, blood–brain barrier