Chronic Kidney Disease and Cerebrovascular Health

Chronic kidney disease (CKD) and cerebrovascular health are intricately connected through shared risk factors, interorgan communication and overlapping pathophysiological pathways. CKD, defined by a sustained reduction in glomerular filtration rate or persistent proteinuria, predisposes individuals to hypertension, vascular stiffness and endothelial dysfunction, all of which elevate the risk of cerebral infarction and haemorrhage. Conversely, acute or chronic cerebrovascular events may precipitate renal injury via neurohormonal activation, systemic inflammation and altered haemodynamics. Emerging evidence highlights oxidative stress, uraemic toxin accumulation and dysregulation of mineral metabolism as non-traditional contributors linking renal impairment to cerebral small-vessel disease, vascular cognitive decline and stroke severity. Globally, the dual burden of CKD and cerebrovascular disease presents a major public health challenge, underscoring the need for integrated screening, risk stratification and targeted interventions that address both renal and cerebral outcomes.

Research from Nature Portfolio

Large-scale community data have demonstrated that both markedly reduced glomerular filtration rate and the presence of proteinuria independently predict higher all-cause mortality. These indicators retain prognostic value after adjustment for traditional risk factors and reveal sex-specific patterns, with women showing particularly elevated risk when both markers are present. In parallel, experimental models have elucidated how pre-existing renal impairment exacerbates cerebral ischaemic injury. Animals with chemically induced CKD exhibit larger infarct volumes, poorer neurobehavioural performance and heightened recruitment of pro-inflammatory microglia (M1 phenotype) within the ischaemic core. Mechanistic investigations implicate reduced activation of AMP-activated protein kinase and concurrent upregulation of NF-κB signalling, suggesting that modulation of these pathways could mitigate stroke severity in the context of CKD.

Chronic Kidney Disease and Cerebrovascular Health publication trend

The graph below shows the total number of articles in chronic kidney disease and cerebrovascular health across all publications each year (not limited to Nature Index journals).

Technical terms

Chronic Kidney Disease (CKD): a condition marked by a persistent reduction in kidney function (eGFR < 60 mL/min/1.73 m²) or evidence of kidney damage (e.g., proteinuria) for at least three months.

Glomerular Filtration Rate (GFR): an estimate of the volume of blood filtered by the glomeruli per minute, serving as a key indicator of renal function.

Proteinuria: the pathological presence of excess protein in the urine, reflecting glomerular or tubular damage and signalling elevated vascular risk.

Acute Ischaemic Stroke (AIS): rapid loss of brain function due to an obstruction of blood vessels supplying the brain, leading to tissue infarction.

AMP-activated Protein Kinase (AMPK): an intracellular energy sensor that regulates metabolic homeostasis and modulates inflammatory responses under stress conditions.

Microglial Polarisation (M1): the pro-inflammatory activation state of microglia characterised by the release of cytokines and reactive oxygen species, contributing to tissue injury after stroke.

References

1. Stroke‐Induced Renal Dysfunction: Underlying Mechanisms and Challenges of the Brain–Kidney Axis. CNS Neuroscience & Therapeutics (2024).
2. Influence of renal function on blood pressure control and outcome in thrombolyzed patients after acute ischemic stroke: post-hoc analysis of the ENCHANTED trial. Frontiers in Endocrinology (2024).
3. Disentangling the multiple links between renal dysfunction and cerebrovascular disease. Journal of Neurology Neurosurgery & Psychiatry (2019).
4. Proteinuria as an independent predictor of stroke: Systematic review and meta-analysis. International Journal of Stroke (2020).
5. Association of estimated glomerular filtration rate and proteinuria with all-cause mortality in community-based population in China: A Result from Kailuan Study. Scientific Reports (2018).
6. Cellular and molecular mechanisms associated with ischemic stroke severity in female mice with chronic kidney disease. Scientific Reports (2019).