Ontogeny of intrinsic innervation in the human kidney

Dina Tiniakos, Valsamo Anagnostou, Stavros Stavrakis, Despoina Karandrea, Emmanouil Agapitos, Christos Kittas

Research output: Contribution to journalArticlepeer-review


We aimed to define, for the first time, the ontogeny of intrarenal innervation and to assess the distribution and nature of parenchymal nerves in the human fetal kidney. Our material consisted of routinely-processed renal tissue sections from 17 human fetuses, six of 20-24 gestational weeks (gw) and 11 of 25-40 gw, and three adults. We used immunohistochemistry with antibodies to the pan-neural markers neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100, and the adrenergic marker tyrosine hydroxylase (TH). NSE-, NF-, S100-, and PGP9.5-positive nerves, associated with arterial and venous vasculature, were identified in the renal cortex from 20 gw onwards, and their density appeared to increase with gestation, reaching adult levels at 28 gw. Most of the intrarenal nerves were TH-positive. Nerve fibers extended from the corticomedullary region to the outer cortex, reaching the renal capsule in the 3rd trimester. In detail, NSE-, NF-, S100-, PGP9.5-, and TH-immunoreactive fibers were observed in close apposition to the renal artery and its branches, occasionally reaching the afferent and efferent arteriole (3rd trimester). Nerve fibers were detected in close apposition to the juxtaglomerular apparatus in the 2nd and 3rd trimesters. In the renal medulla, NSE-, PGP9.5-, S100-, and TH-positive nerve fibers were detected close to tubular cells as early as 20 gw. However, their density gradually decreased during the 3rd trimester, and they were not observed in the medulla of the adult kidney. In conclusion, the human fetal kidney appears richly innervated during the 2nd and 3rd trimesters. There is a progressive increase in the density of parenchymal nerve fibers towards term from the corticomedullary region to the cortex. Most intrarenal nerves are adrenergic and have a predominant perivascular distribution, implying that renal innervation plays an important functional role during intrauterine life.

Original languageEnglish (US)
Pages (from-to)41-47
Number of pages7
JournalAnatomy and Embryology
Issue number1
StatePublished - Nov 1 2004
Externally publishedYes


  • Development
  • Fetal
  • Immunohistochemistry
  • Intraparenchymal nerves
  • Kidney

ASJC Scopus subject areas

  • Anatomy
  • Embryology
  • Developmental Biology
  • Cell Biology

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