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bioRxiv · 10.1101/2024.12.09.627590

Effects of Disease on Renal Blood Flow Regulation: Assessing Autoregulation Disruption

Maddineni, B.·Versypt, A. N. F.
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Abstract

The functioning of kidneys on blood flow regulation was investigated, particularly under diseased conditions such as chronic kidney disease, which includes conditions of diabetic nephropathy and other glomerular damage. A mathematical model was developed to better understand how variations based on the glomerular filtration rate impact key kidney function outputs, such as afferent arteriolar diameter, smooth muscle activation, and the chloride ion concentration at the macula densa. We have analyzed these factors by considering the dynamics of the mathematical model of ordinary and partial differential equations to study blood flow control in the kidney, which has provided new insights into the maintenance of autoregulation. By simulating the processes of renal blood flow--specifically through the afferent arteriole and glomerulus, and detailing the process of chloride transport within the renal tubule--the model offers a comprehensive view of how the kidney regulates glomerular filtration rate amidst fluctuating systemic blood pressures and disease-specific changes. Central to this model are the myogenic response that adjusts afferent arteriole muscle tone in reaction to pressure changes and the tubuloglomerular feedback, which controls arteriole size based on chloride levels at the macula densa. The models simulations reveal the robustness of renal autoregulation across a spectrum of chronic kidney disease stages, showing stability under normal conditions but indicating a breakdown in regulation with advanced chronic kidney disease. This breakdown is attributed to disruptions in the vascular and feedback systems. The findings from this model shed light on the progression of renal dysfunction in chronic kidney disease and underscore the potential for developing targeted treatments to maintain kidney health.

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Maddineni, B., Versypt, A. N. F.. 2024-12-15. Effects of Disease on Renal Blood Flow Regulation: Assessing Autoregulation Disruption. https://doi.org/10.1101/2024.12.09.627590

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