Three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespan

Liam McLaughlin, Bo Zhang, Siddharth Sharma, Amanda L. Knoten, Madhurima Kaushal, Jeffrey M. Purkerson, Heidie L. Huyck, Gloria S. Pryhuber, Joseph P. Gaut and Sanjay Jain ()
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Liam McLaughlin: Washington University School of Medicine
Bo Zhang: Washington University School of Medicine
Siddharth Sharma: Washington University School of Medicine
Amanda L. Knoten: Washington University School of Medicine
Madhurima Kaushal: Washington University School of Medicine
Jeffrey M. Purkerson: University of Rochester Medical Center
Heidie L. Huyck: University of Rochester Medical Center
Gloria S. Pryhuber: University of Rochester Medical Center
Joseph P. Gaut: Washington University School of Medicine
Sanjay Jain: Washington University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: Abstract The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural organization enables coordinated functions like filtration, absorption, and blood pressure regulation. Our analysis revealed developmental changes in glomerular orientation, density, volume, and innervation from birth through aging. We discovered an extensive nerve network connecting different nephron segments and organizing glomeruli into distinct communities. These communities are linked through “mother glomeruli” that serve as control centers, creating a repeating pattern throughout the cortex. This sophisticated neural organization, which is underdeveloped in newborn kidneys and disrupted in conditions like diabetes and hydronephrosis, appears to facilitate synchronized responses to maintain fluid balance. The findings provide insights into how the kidney’s structural architecture enables coordinated function across its numerous nephrons.

Date: 2025
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DOI: 10.1038/s41467-025-60435-8

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