Stroke-Induced Renal Dysfunction: Underlying Mechanisms and Challenges of the Brain-Kidney Axis

Abstract

Stroke, a major neurological disorder and a leading cause of disability and death, often inflicts damage upon other organs, particularly the kidneys. While chronic kidney disease (CKD) has long been established as a significant risk factor for cerebrovascular disease, stroke can induce renal dysfunction, manifesting as acute kidney injury (AKI) or CKD. Mounting clinical and basic research evidence supports the existence of a bidirectional brain-kidney crosstalk following stroke, implicating specific mechanisms and pathways in stroke-related renal dysfunction. This review analyzes pertinent experimental studies, elucidating the underlying mechanisms of this cerebro-renal interaction following stroke. Additionally, we summarize the current landscape of clinical research investigating brain-kidney interplay and discuss potential challenges in the future. By enhancing our understanding of the scientific underpinnings of brain-kidney crosstalk, this review paves the way for improved treatment strategies and outcomes for stroke patients. Recognizing the intricate interplay between the brain and kidneys after stroke holds profound clinical implications.

Keywords: AKI; CKD; brain–kidney interaction; renal dysfunction; stroke.

FIGURE 1

This chart lists relevant clinical manifestations and abnormal examination results that may be seen in patients with post‐stroke kidney injury.

FIGURE 2

Schematic of the pathologic process of AKI and CKD after stroke. This diagram illustrates the changes that occur in renal tubular tissue following a stroke, leading to AKI and CKD. Initially, the kidneys experience ischemia and hypoxia due to high vascular resistance, which can result in acute tubular cell necrosis and endothelial cell damage, causing AKI. In the mid to late phase, brain macrophages are activated and released into the blood, further causing activation of peripheral immune cells (e.g., renal resident macrophages) as well as neutrophil recruitment. Large numbers of leukocytes infiltrate the kidney, M1 phenotype macrophages are continuously expressed, and maladaptive repair of the renal tubules occurs. Stimulated by pro‐inflammatory and other injury factors, pericytes separate from the endothelium, resulting in capillary thinning. Additionally, epithelial or endothelial cells may undergo epithelial‐mesenchymal transition (EMT), transforming into mesenchymal cells through TGF‐β1 signal pathway activation and overexpression of MiRs. Pericytes proliferate and differentiate to produce myofibroblasts, which promote collagen deposition in the kidney and cause renal fibrosis, ultimately leading to and the development of CKD.

FIGURE 3

Schematic overview of the mechanisms and pathways involved in renal impairment after stroke. Renal impairment after stroke involves two major pathways: The inflammatory immune pathway and the neurohumoral pathway. In the inflammatory immune pathway, the BBB is compromised after stroke, leading to the release of pro‐inflammatory substances from the brain into the blood and the activation of peripheral inflammatory immune responses. The neurohumoral pathway involves the activation of the RAAS axis, the HTPA axis and the SNS. Multiple vasoconstrictor substances and related hormones act on receptor targets, resulting in hemodynamic disturbances and an acute ischemic state in the kidney. Multiple mechanisms promote the development of AKI or CKD in the kidney, while stroke as an acute injury promotes the progression of AKI to CKD.