Anatomic Patterns of Renal Arterial Sympathetic Innervation: New Aspects for Renal Denervation

Initial studies of catheter-based renal arterial sympathetic denervation to lower blood pressure in resistant hypertensive patients renewed interest in the sympathetic nervous system's role in the pathogenesis of hypertension. However, the SYMPLICITY HTN-3 study failed to meet its prespecified blood pressure lowering efficacy endpoint. To date, only a limited number of studies have described the microanatomy of renal nerves, of which, only two involve humans.

Renal arteries were harvested from 15 cadavers from the Klinikum Osnabruck and Schuchtermann Klinik, Bad Rothenfelde. Each artery was divided longitudinally in equal thirds (proximal, middle, and distal), with each section then divided into equal superior, inferior, anterior, and posterior quadrants, which were then stained. Segments containing no renal nerves were given a score value = 0, 1-2 nerves with diameter <300 µm a score = 1; 3-4 nerves or nerve diameter 300-599 µm a score = 2, and >4 nerves or nerve diameter ≥600 µm a score = 3. A total of 22 renal arteries (9 right-sided, 13 left-sided) were suitable for examination. Overall, 691 sections of 5 mm thickness were prepared. Right renal arteries had significantly higher mean innervation grade (1.56 ± 0.85) compared to left renal arteries (1.09 ± 0.87) (P < 0.001). Medial (1.30 ± 0.59) and distal (1.39 ± 0.62) innervation was higher than the proximal (1.17 ± 0.55) segments (p < 0.001). When divided in quadrants, the anterior (1.52 ± 0.96) and superior (1.71 ± 0.89) segments were more innervated compared to posterior (0.96 ± 0.72) and inferior (0.90 ± 0.68) segments (P < 0.001).

That the right renal artery has significantly higher innervation scores than the left. The anterior and superior quadrants of the renal arteries scored higher in innervation than the posterior and inferior quadrants did. The distal third of the renal arteries are more innervated than the more proximal segments. These findings warrant further evaluation of the spatial innervation patterns of the renal artery in order to understand how it may enhance catheter-based renal arterial denervation procedural strategy and outcomes.

The SYMPLICITY HTN-3 study dealt a blow to the idea of the catheter-based renal arterial sympathetic denervation. We investigated the location and patterns of periarterial renal nerves in cadaveric human renal arteries. To quantify the density of the renal nerves we created a novel innervation score. On average the right renal arteries were significantly more densely innervated than the left renal arteries, the anterior and superior segments were significantly more innervated compared to the posterior and inferior segments, absolute innervation scores in the proximal third of the left or right renal arteries were always lower when compared to distal segments. These findings may enhance catheter-based renal arterial denervation procedural strategy and outcomes.