Autonomic cardiovascular alterations as therapeutic targets in chronic kidney disease

Purpose The present paper will review the impact of different therapeutic interventions on the autonomic dysfunction characterizing chronic renal failure. Methods We reviewed the results of the studies carried out in the last few years examining the effects of standard pharmacologic treatment, hemodialysis, kidney transplantation, renal nerve ablation and carotid baroreceptor stimulation on parasympathetic and sympathetic control of the cardiovascular system in patients with renal failure. Results Drugs acting on the renin–angiotensin system as well as central sympatholytic agents have been documented to improve autonomic cardiovascular control. This has also been shown for hemodialysis, although with more heterogeneous results related to the type of dialytic procedure adopted. Kidney transplantation, in contrast, particularly when performed together with the surgical removal of the native diseased kidneys, has been shown to cause profound sympathoinhibitory effects. Finally, a small amount of promising data are available on the potential favorable autonomic effects (particularly the sympathetic ones) of renal nerve ablation and carotid baroreceptor stimulation in chronic kidney disease. Conclusions Further studies are needed to clarify several aspects of the autonomic responses to therapeutic interventions in chronic renal disease. These include (1) the potential to normalize sympathetic activity in uremic patients by the various therapeutic approaches and (2) the definition of the degree of sympathetic deactivation to be achieved during treatment.

Function of Renal Nerves in Kidney Physiology and Pathophysiology

Renal sympathetic (efferent) nerves play an important role in the regulation of renal function, including glomerular filtration, sodium reabsorption, and renin release. The kidney is also innervated by sensory (afferent) nerves that relay information to the brain to modulate sympathetic outflow. Hypertension and other cardiometabolic diseases are linked to overactivity of renal sympathetic and sensory nerves, but our mechanistic understanding of these relationships is limited. Clinical trials of catheter-based renal nerve ablation to treat hypertension have yielded promising results. Therefore, a greater understanding of how renal nerves control the kidney under physiological and pathophysiological conditions is needed. In this review, we provide an overview of the current knowledge of the anatomy of efferent and afferent renal nerves and their functions in normal and pathophysiological conditions. We also suggest further avenues of research for development of novel therapies targeting the renal nerves.

Evaluation of Later Morphologic Alterations in Renal Artery Wall and Renal Nerves in Response to Catheter-Based Renal Denervation in Sheep: Comparison of the Single-Point and Multiple-Point Ablation Catheters

This study evaluated the subacute morphologic alterations in renal artery wall and renal nerves in response to catheter-based renal denervation (RDN) in sheep and also compared the efficiency of single-point and multiple-point ablation catheters. Effect of each ablation catheter approved for the clinical use (Symplicity FlexTM, Medtronic, Inc., or EnligHTNTM, St. Jude Medical, INC.) was compared to intact contralateral renal artery in 12 sheep by histopathology and immunohistochemistry evaluation after a 10-day period post-RDN procedure. The safety was verified by extensive evaluation of kidney morphology. Vascular wall lesions and nerve injuries were more pronounced in those animals treated with multi-point EnligHTN catheter when compared with animals treated with single-point Symplicity Flex catheter. However, neither RDN procedure led to complete renal nerve ablation. Both systems, tested in the present study, provided only incomplete renal nerve ablation in sheep. Moreover, no appreciable progression of the nerve disintegration in subacute phase post-RDN procedure was observed. This study further supports the notion that the effectiveness remains fully dependent on anatomical inter-individual variability of the sympathetic nerve plexus accompanying the renal artery. Therefore, new systems providing deeper penetrance to targeted perivascular structure would be more efficient.