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Peripheral neurons innervate the kidney and help maintain physiological homeostasis. Their altered activity can also have pathophysiological consequences. However, our knowledge of the role kidney nerves play in disease is primarily related to hypertension, highlighting a significant gap in our understanding of other disease states and an area that has been largely ignored. The kidney is innervated by both sympathetic and sensory neurons, with the latter only recently being recognized as a significant constituent of the overall network. Our group has pioneered whole tissue imaging of the kidney to visualize these networks in 3D. While we have a greater understanding of kidney innervation under normal conditions, we predict that their organization is significantly altered in kidney disease and parallels histological and functional changes. Through a careful mapping of the kidney nerve network from acute kidney injury to chronic kidney disease, we will uncover for the first time how their organization and associations with a variety of kidney cell targets change across time. We will address whether an imbalance of sympathetic versus sensory innervation and thereby proper modulation of activity may drive disease progression. Additionally, these data will provide the first whole tissue mapping of injury and disease progression with the ability to identify significant spatiotemporal changes to nephrons, immune cells, and vasculature that cannot be discerned from tissue sections. Our studies have the potential to shift our experimental and clinical approaches and consider how nerve-kidney associations impact disease. Modulating kidney nerves post-injury could slow or stop disease progression, or even promote repair, providing new therapeutic options which are currently lacking.
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