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Review
. 2025 Apr;56(4):1069-1081.
doi: 10.1161/STROKEAHA.124.047070. Epub 2025 Jan 24.

The Kidney-Immune-Brain Axis: The Role of Inflammation in the Pathogenesis and Treatment of Stroke in Chronic Kidney Disease

Dearbhla M Kelly  1 , Eoin M Kelleher  2 , Peter M Rothwell  1
Affiliations
Review

The Kidney-Immune-Brain Axis: The Role of Inflammation in the Pathogenesis and Treatment of Stroke in Chronic Kidney Disease

Dearbhla M Kelly et al. Stroke. 2025 Apr.

Abstract

Cardiovascular diseases such as stroke are a major cause of morbidity and mortality for patients with chronic kidney disease (CKD). The underlying mechanisms connecting CKD and cardiovascular disease are yet to be fully elucidated, but inflammation is proposed to play an important role based on genetic association studies, studies of inflammatory biomarkers, and clinical trials of anti-inflammatory drug targets. There are multiple sources of both endogenous and exogenous inflammation in CKD, including increased production and decreased clearance of proinflammatory cytokines, oxidative stress, metabolic acidosis, chronic and recurrent infections, dialysis access, changes in adipose tissue metabolism, and disruptions in intestinal microbiota. This review focuses on the mechanisms of inflammation in CKD, dialysis and associated therapies, its proposed impact on stroke pathogenesis and prognosis, and the potential role of anti-inflammatory agents in the prevention and treatment of stroke in patients with CKD.

Keywords: cardiovascular diseases; inflammation; renal dialysis; renal insufficiency, chronic; stroke.

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Conflict of interest statement

Dr Rothwell has in the past provided consultancy services for Abbott Vascular, Bayer, Bristol-Myers Squibb, and Sanofi US Services. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Sources of inflammation in chronic kidney disease (CKD). PAMPs indicate pathogen-associated molecular patterns.
Figure 2.
Figure 2.
Evidence supportive of the inflammatory hypothesis for stroke in chronic kidney disease (CKD). CRP indicates C-reactive protein; IL, interleukin; MPO, myeloproteinase; and TNF, tumor necrosis factor.
Figure 3.
Figure 3.
Proposed inflammatory targets and therapeutic strategies based on chronic kidney disease (CKD) stage and progression. CV indicates cardiovascular; GFR, glomerular filtration rate; GLP-1-RA, glucagon-like peptide-1 receptor agonist; IL, interleukin; nsMRA, nonsteroidal mineralocorticoid receptor antagonist; RAAS, renin-angiotensin-aldosterone system; ROS, reactive oxygen species; SGLT2i, sodium-glucose cotransporter 2 inhibitor; and T2DM, type 2 diabetes.
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