Progressive chronic kidney disease contributes to elevated cell death mechanisms and aggravates post-stroke severity

Area of Science:

• Nephrology
• Neurology
• Cardiovascular Science

Background:

• Chronic kidney disease (CKD) is a significant risk factor that exacerbates outcomes following ischemic stroke.
• Understanding the direct impact of CKD progression on stroke pathophysiology is crucial for improving patient care.

Purpose of the Study:

• To characterize a gradient-progressive chronic kidney disease (CKD) mouse model.
• To evaluate the impact of varying CKD severity on ischemic stroke outcomes.
• To elucidate the mechanisms underlying CKD-associated stroke complications.

Main Methods:

• Adenine injections were used to induce progressive CKD in C57BL/6 mice over 4 weeks, monitored by ultrasound and blood chemistry.
• Transient focal ischemia was induced at 2 and 4 weeks of CKD, with brain damage assessed by MRI.
• Cerebral blood flow, oxygen saturation, cardiac function, bone density, motor function, survival, and proteomic changes were evaluated.

Main Results:

• Progressive CKD led to severe brain damage and poor stroke outcomes, irrespective of CKD stage.
• These detrimental effects were attributed to direct vascular damage in the brain, not altered blood flow dynamics.
• Altered markers of kidney dysfunction and coagulant status were observed post-stroke in CKD mice.

Conclusions:

• This study presents the first progressive CKD mouse model to assess synergistic stroke outcomes.
• CKD directly impacts brain vasculature, leading to worsened stroke outcomes independent of flow dynamics.
• The findings highlight the critical need to manage CKD in stroke patients to mitigate severe complications.