Piezo2 is a mechanically activated ion channel expressed in a subset of sensory neurons, including in the bladder. Our lab has recently mapped innervation of the developing kidney and found that renal nerve development begins at embryonic day 13.5 (E13.5) and is tightly aligned with smooth muscle actin (SMA+) arterial development. However, the presence and spatiotemporal innervation of Piezo2+ sensory nerves in the kidney remains unknown. In the current study, we hypothesized that Piezo2+ sensory nerves would be present early in kidney development adjacent developing nephrons and that these axons innervating the kidney could be traced back to Piezo2+ cell bodies in the dorsal root ganglia (DRGS). To test this hypothesis, we performed immunofluorescent staining to label all nerves (Tubb3+, pan-neuronal marker) and Piezo2 in kidneys from wildtype mice at early (E13.5), mid (E15.5) and late (post-natal day 0, P0) nephrogenesis. To determine the signaling pathways of Piezo2+ nerves in the kidney to the peripheral nervous system (PNS), we utilized retrograde tracing with a Cre-driven fluorescently (pAAV-Flex-tdTomato) labeled virus injected into the kidney of heterozygous Piezo2Cre/+ adult mice (n=4, 10 weeks). The injected kidney, the contralateral control, and cervical to sacral DRGs were collected and fluorescent imaging was performed with confocal microscopy. We found that by E15.5, Piezo2+ sensory nerves were present in the developing kidney which constitute a small subset of all nerves (Tubb3+). These Tubb3+Piezo2+ sensory nerves persist through nephrogenesis (P0) and in the adult mouse kidney. Piezo2+ sensory nerves were found in nerve bundles running along SMA+ vasculature as well as observed adjacent glomeruli (Nphs2+) and proximal tubules (Lrp2+). Importantly, we also identified Piezo2+ sensory nerves in the renal cortex from human kidney samples. Retrograde tracing experiments revealed Piezo2+ sensory nerves in the kidney originate from lower thoracic and lumbar DRGs. Taken together, these data suggest that Piezo2+ sensory nerves are present in the mouse and human kidney and are capable of transmitting signals back to the PNS. As Piezo2 is known to be expressed in juxtaglomerular cells, Piezo2+ sensory nerves observed in close proximity suggests a previously unrecognized kidney cell-nerve crosstalk. Future studies will investigate Piezo2+ sensory activity and feedback in the kidney to understand the role of Piezo2 in renal mechanosenstion. NIH R01DK121014 to LO. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.