# Afferent innervation of the kidney: projections to and processing in the central nervous system

**Authors:** Brianna Dailey-Krempel, Louise C. Evans, John W. Osborn, Lucy Vulchanova

PMC · DOI: 10.3389/fphys.2025.1743631 · Frontiers in Physiology · 2026-02-05

## TL;DR

This review explores how sensory nerves in the kidney connect to the brain and spinal cord, and their role in hypertension and other conditions.

## Contribution

The paper provides a comprehensive review of the anatomy and central processing of renal afferent nerves in hypertension.

## Key findings

- Renal afferent nerves project to the spinal cord and caudal brainstem via dorsal root ganglia.
- Potential involvement of the paraventricular nucleus and nucleus of the solitary tract in processing renal sensory input.
- Renal afferents may contribute to hypertension through mechanosensitive and chemosensitive subtypes.

## Abstract

FDA approval for catheter-based renal nerve ablation has sparked renewed interest in the role of renal nerves in hypertension and their potential contribution to other pathophysiologies. While the anti-hypertensive effects of catheter-based renal nerve ablation were thought to be due to the ablation of the sympathetic efferent nerves going to the kidney, preclinical hypertensive rodent studies and unexpected beneficial clinical outcomes have highlighted the renal afferent (sensory) nerves as a contributor to the pathogenesis of hypertension. Renal afferents are most abundant in the renal pelvis but also innervate the renal cortex. Their neurochemical and functional diversity remains to be fully elucidated. Tracing studies from the kidney to the central nervous system (CNS) have identified direct projections of spinal afferents with cell bodies in dorsal root ganglia to both the spinal cord and caudal brainstem. Few studies have suggested vagal innervation of the kidney with cell bodies in the nodose ganglia. The central processing of renal afferent input in brain autonomic circuits is not thoroughly understood. Regions involved in renal afferent input processing include the paraventricular nucleus of the hypothalamus and nucleus of the solitary tract which integrate peripheral sensory inputs with central homeostatic sensing regions including circumventricular organs. This review aims to summarize our current understanding of renal afferent anatomy including tracing and immunolabeling studies from the kidney to the CNS, the general mechanosensitive and chemosensitive subtypes in the kidney, and broadly discuss a potential pathway for the central processing of renal afferent input through autonomic and other homeostatic nuclei.

## Full-text entities

- **Genes:** Tff2 (trefoil factor 2) [NCBI Gene 116592], Pnmt (phenylethanolamine-N-methyltransferase) [NCBI Gene 24661], Sst (somatostatin) [NCBI Gene 24797] {aka SRIF, SS-14, SS-28, Smst}, NOS1 (nitric oxide synthase 1) [NCBI Gene 4842] {aka IHPS1, N-NOS, NC-NOS, NOS, bNOS, nNOS}, Slc17a6 (solute carrier family 17 member 6) [NCBI Gene 84487] {aka Dnpi, Vglut2}, Trpv1 (transient receptor potential cation channel, subfamily V, member 1) [NCBI Gene 83810] {aka TRPV1_SON, VR.5'sv, Vr1, Vr1l1}, Trpv1 (transient receptor potential cation channel, subfamily V, member 1) [NCBI Gene 193034] {aka OTRPC1, TRPV1alpha, TRPV1beta, VR-1, Vr1}, Calca (calcitonin/calcitonin-related polypeptide, alpha) [NCBI Gene 12310] {aka CA, CGRP-1, CGRP1, Calc, Calc1, Cgrp}, Chat (choline O-acetyltransferase) [NCBI Gene 290567], Vip (vasoactive intestinal peptide) [NCBI Gene 117064] {aka vip/phi27}, Nos1 (nitric oxide synthase 1) [NCBI Gene 24598] {aka bNOS}, Prph (peripherin) [NCBI Gene 24688] {aka Perf, Prph1}, Calca (calcitonin-related polypeptide alpha) [NCBI Gene 24241] {aka CAL6, CGRP, CGRP1, Cal1, Calc, RATCAL6}, Nts (neurotensin) [NCBI Gene 299757], OXT (oxytocin/neurophysin I prepropeptide) [NCBI Gene 5020] {aka OT, OT-NPI, OXT-NPI}, Th (tyrosine hydroxylase) [NCBI Gene 25085] {aka The}, Npy (neuropeptide Y) [NCBI Gene 24604] {aka NPY02, RATNPY, RATNPY02}, AVP (arginine vasopressin) [NCBI Gene 551] {aka ADH, ARVP, AVP-NPII, AVRP, VP}
- **Diseases:** cardiac arrhythmias (MESH:D001145), hypoxic (MESH:D002534), ischemia (MESH:D007511), hypotension (MESH:D007022), anoxia (MESH:D000860), renal inflammation (MESH:D007249), pain (MESH:D010146), heart failure (MESH:D006333), depression (MESH:D003866), compression of the kidney (MESH:D007674), sleep apnea (MESH:D012891), epilepsy (MESH:D004827), renal vein occlusion (MESH:D012170), occlusion (MESH:D001157), hypertension (MESH:D006973), asphyxia (MESH:D001237)
- **Chemicals:** 6-hydroxy-dopamine (MESH:D016627), water (MESH:D014867), Fast Blue (MESH:C031455), glutamate (MESH:D018698), GABA (MESH:D005680), glycolipid (MESH:D006017), NaCl (MESH:D012965), mannitol (MESH:D008353), KCl (MESH:D011189), glucose (MESH:D005947), Serotonin (MESH:D012701), Alexa Fluorophore (-), True Blue (MESH:C038675), sodium (MESH:D012964), potassium (MESH:D011188), urea (MESH:D014508), FluoroGold (MESH:C049774), catecholamine (MESH:D002395)
- **Species:** Ovis aries (domestic sheep, species) [taxon 9940], Sus scrofa (pig, species) [taxon 9823], Adeno-associated virus (species) [taxon 272636], Mus musculus (house mouse, species) [taxon 10090], Suid alphaherpesvirus 1 (no rank) [taxon 10345], Canis lupus familiaris (dog, subspecies) [taxon 9615], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Cavia porcellus (domestic guinea pig, species) [taxon 10141], Rattus norvegicus (brown rat, species) [taxon 10116], Felis catus (cat, species) [taxon 9685], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** T13

## Full text

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## Figures

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## References

106 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916394/full.md

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Source: https://tomesphere.com/paper/PMC12916394