1. Aloke Finn, M.D. CVPath Institute Inc. Gaithersburg, MD, USA
Preclinical Evaluation of the Renal Nerve:
Anatomy, Renal Nerve Distribution and Animal Models
Aloke Finn, M.D.
CVPath Institute Inc.
Gaithersburg, MD, USA

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Employment in industry: No
Honorarium: Abbott Vascular, Boston Scientific,
Lutonix, Terumo Corporation, and W.L. Gore.
Institutional grant/research support: 480 Biomedical, Abbott Vascular, Atrium,
BioSensors International, Biotronik, Boston Scientific,
Cordis J&J, GSK, Kona, Medtronic, MicroPort Medical,
CeloNova, OrbusNeich Medical, ReCore,
SINO Medical Technology, Terumo Corporation,
and W.L. Gore.
Owner of a healthcare company: No
Stockholder of a healthcare company: No

3. Cumulative Distance From Nerves to Lumen
90th percentile
Proximal 6.77 mm / Middle 6.64 mm /Distal 5.27 mm
75th percentile
Proximal 4.67 mm / Middle 4.49 mm / Distal 3.24 mm
75% of sympathetic nerves located a mean of 4.28 mm from lumen
50th percentile
Proximal 2.84 mm / Middle 2.58 mm / Distal 1.81 mm
Cumulative percentile of nerves
Distance from arterial lumen (mm)
Sakakura K, et al. J Am Coll Cardiol 2014

4. Distance from lumen to nerve (mm) Renal Artery Diameter (mm)
Proximal
Middle
Distal
Post Bifurcation
Total
0-<1
218
244
227
801
1490
1-<2
831
892
877
1023
3623
2-<3
549
553
324
261
1687
3-<4
469
372
213 97
1151
4-<5
314
284
133 54
785
5-<6
249
203
115 29
596
6-<7
163
169 39 15
386
7-<8
120 86 36 4
246
8-<9 91 71 7
198
9-<10 58 14
150
≥10 8 1 17
Total No. of nerves
3070
2952
2008
2299
10329
No. of arterial section 82 76 62 80
300
Renal Artery Diameter (mm)
4.4±0.9
4.0±0.7
4.1±0.9
3.6±1.4
63%
Sakakura K, et al., JACC :634-43
p<0.05
Post
bifurcation
14.7/artery

5. Proposed Diagram of Renal Artery and Circumferential Peri-Arterial Nerve Location
Sakakura K, et al., JACC :634-43

6. Distribution and Density of Renal Sympathetic Nerves
Distribution of nerves stratified according to total number (each green dot represents 10 nerves), relative number as percent per segment, and distance from the lumen in relative (A) proximal, (B) middle, and (C) distal location. Figure prepared using raw data from Sakakura et al. (4), and from raw data provided by M. Joner

7. Renal artery (accessary)
Distribution of Nerve
Aorticorenal
ganglion
Renal artery (accessary)
Renal artery
Renal plexus
overlying
renal arteries
Aortic plexus
Lusch A et al., J Urol Apr;191(4):

8. Variation in Anatomy Among Human and Pig Renal Arteries
Human renal artery – anatomical variants
About 70% of the population have a single renal artery1
Accessory renal arteries are the most common variant present in about 1/3 of the population2
Prehilar (early) branching is a normal variant and present in about 10-20% of the population (32% on right RA, 25% on left RA and 22% on both sides)3,4,5
Pig renal arteries more often have early branches
1Hazirolan et al., Diagn Interv Radiol, 2011
2Kadir et al., Diagn Angiography, 1986
3Özkan et al., Diagn Interv Radiol, 2006
4Chai et al., Korean J Radiol, 2008
5Patil et al., Nephrol Dial Transplant, 2001

9. Distribution of Nerves in Accessory Renal Arteries
Aorta
Accessory Renal Artery
Korean J Radiol. 2010; 11(3): 346–354
Sakakura K, et al., JACC :634-43

10. Assessment of Renal Nerves in a Healthy Swine Model
Proximal
Middle
Distal
Post 1
Post 2
Post-bifurcation
1st bifurcation
2nd bifurcation
Diameter of nerves (shortest)
Aorta
Renal artery
Kidney
Distance from lumen of renal artery to nerve
Ureter

11. Mean number of nerves per artery Intermediate Nerves (≥50 µm)
The Percentage of Nerves Stratified by Distance from Lumen of Renal Artery
Proximal
6 mm
Distal
4 mm
2 mm
Mean number of nerves per artery
Any size
Proximal
Middle
Distal
Post 1
Post 2
≤2 mm 22 23 30
2-4mm 14 11 10 3 4
4-6mm 7 5
>6mm 2
Any nerves
(%)
(%)
Intermediate Nerves (≥50 µm)
88%
88%
86%
99%
96%
58%
62%
52%
38%
32%
Prox
Mid
Dist
Post 1
Post 2
Prox
Mid
Dist
Post 1
Post 2

12. Mean number of nerves per artery
(nerves divided by number of arteries in post bifurcation sections)
Mean number of nerves (≥50 µm) within 2 mm per artery
P = 0.001
4.3
5.5
6.8
4.0
2.5
Prox
Mid
Dist
Post 1
Post 2
The largest proportion of intermediate size nerves are found in the distal main renal artery close to the bifurcation

13. Anatomy of Renal Sympathetic Nerves in a Healthy Swine Model
Ganglion
Nerve size is greater in proximal than distal and post-bifurcation
Nerves are located close to the renal artery in distal and post-bifurcation compared to proximal segments.
Nerves also branch at the site of bifurcation.
Target for ablation
Aorta
Renal artery
Kidney
1st bifurcation
2nd bifurcation
Ureter

14. Summary
Maximum number of Nerves are located close to the distal renal artery.
The size of nerves diminishes from proximal to distal and post-bifurcation renal artery segments
intermediate size nerves (≥50μm) are most frequently located within 2mm of the renal artery lumen in the distal and post-bifurcation segments
The maximum number of intermediate sized (>50μm) nerves within 2mm are in the distal main renal artery
Therefore, renal denervation should be performed in the distal main renal artery, with or without the middle or proximal renal arteries.

15. Acknowledgments Funding CVPath Institute CVPath Institute Inc.
Kazuyuki Yahagi, MD
Hiroyoshi Mori, MD
Sho Torii, MD, PhD
Emanuel Harari, MD
Maria Romero, MD
Robert Kutz, MS
Russ Jones
Abebe Atiso, HT
Jinky Beyer
Lila Adams, HT
Frank D Kolodgie, PhD
Aloke V. Finn, MD
Washington DC