Histological examination of renal nerve distribution, density, and function in humans

Background: Renal denervation is optimised when guided by knowledge of nerve distribution.Aims: We aimed to assess sympathetic nerve distribution along the renal arteries, especially in post-bifurcation vessel segments.Methods: Renal arteries and surrounding tissue from 10 body donors were collected and examined histologically. Immunohistochemical staining was used to analyse nerve distribution and to identify afferent and efferent sympathetic nerves.Results: A total of 6,781 nerves surrounding 18 renal arteries were evaluated. The mean lumen-nerve distance of the left renal artery (2.32 +/- 1.95 mm) was slightly greater than the right (2.29 +/- 2.03 mm; p=0.161); this varied across the arteries' courses: 3.7 +/- 2.3 mm in proximal segments, 2.5 +/- 2.0 mm in middle segments, 1.9 +/- 1.6 mm in distal prebifurcation segments and 1.3 +/- 1.0 mm in post-bifurcation segments (p<0.001). The number of nerves per quadrant was highest in the proximal segments (13.7 +/- 18.6), followed by the middle (9.7 +/- 7.9), distal prebifurcation (8.0 +/- 7.6), and distal post-bifurcation (4.3 +/- 4.0) segments (p<0.001). Circumferentially, the number of nerves was highest in the superior (7.8 +/- 9.4) and the ventral (7.6 +/- 13.1) quadrants (p=0.638). The mean tyrosine hydroxylase (TH) to calcitonin gene-related peptide (CGRP) ratio increased from proximal (37.5 +/- 33.5) to distal (72.0 +/- 7.2 in the post-bifurcation segments; p<0.001). Thirty-eight neuroganglia were identified along 14 (78%) renal arteries.Conclusions: Nerves converge to the renal arteries' lumen in the distal segments and along branches, resulting in the lowest number of nerves per quadrant and the shortest lumen-nerve distance in the distal post-bifurcation segments. Efferent nerves occur predominantly, and the ratio of efferent to afferent nerves continues to increase in the vessels' course.