Background: Renal denervation can lower blood pressure in patients with hypertension. Data on nerve distribution along renal arteries is scarce. An in-depth understanding of renal nerve distribution and density may help to further optimize the procedure technique and technology.

Aims: To assess the nerve distribution along renal arteries (RA), especially in post-bifurcation vessel segments in human cadavers.

Methods: The RA and the surrounding tissue of ten body donors were collected and histologically examined. Immunohistochemical staining was used to analyze nerve size and distribution and to identify afferent (calcitonin gene-related peptide-positive, CGRP) and efferent (tyrosine hydroxylase-positive, TH) sympathetic nerve fibers.

Results: A total of 6888 nerves surrounding 18 RA (two patients had a history of unilateral nephrectomy) were evaluated. The mean lumen-nerve distance in the proximal (n= 919), middle (n= 826), distal pre-bifurcation (n= 576), and distal post-bifurcation (n= 1186) segments was 3.7 (standard deviation: 2.3) mm, 2.5 (2.0) mm, 1.9 (1.6) mm and 1.3 (1.0) mm (p<0.001 for comparison between segments), respectively (figure). Medium-sized (diameter 70-140 µm) and large nerves (>140 µm) were most frequently located in the proximal segment, and their frequency decreased along the RA. The portion of small nerves (35-70 µm) was highest in the distal segments. Nerve fiber density in ratio to analyzed tissue was highest in the distal post-bifurcation segment (70.9 nerve fibers/cm²), followed by the middle (66.3 nerve fibers/cm²), distal pre-bifurcation (60.2 nerve fibers/cm²), and proximal (54.0 nerve fibers/cm²) segments (p=0.001). Nerve density was higher in the ventral (76.5 nerve fibers/cm²) than in the inferior (65.3 nerve fibers/cm²), superior (63.5 nerve fibers/cm²), and dorsal (59.6 nerve fibers/cm²) quadrants (p=0.669). The mean TH-to-CGRP ratio increased from proximal to distal (proximal segment 37.5 (33.5), middle 56.0 (48.3), distal pre-bifurcation 70.2 (46.0), and distal post-bifurcation 72.0 (57.2), respectively (p<0.001). Thirty-eight neuroganglia were identified in 14 of 18 (78%) RA, of which most were in the proximal (47.4%) and middle segments (34.2%) and the ventral quadrant (31.6%).

Conclusion: Nerve fibers converge to the lumen of RA in the distal segments and branch, resulting in the highest density and shortest lumen-nerve distance in the distal post-bifurcation segments. Efferent nerve fibers occur predominantly, and the ratio of efferent to afferent nerve fibers continues to increase in the vessels' course. These findings will help to optimize procedural performance further.