The kidneys are composed of a (near) million functional units, or nephrons, working in parallel to perform their homeostatic functions. The complex 3-dimensional (3D) architecture of the nephron network, along with the multicellular composition as well as distinct functions of nephron segments, challenges our understanding of how the concerted responses of hundreds of thousands of nephrons maintain kidney function, and ultimately whole-body homeostasis. Inter-nephron cross-talk is known to be fundamental in key kidney functions, including the regulation of blood flow and glomerular filtration rate.