309Activation of the efferent fibers leads to blood pressure increase. Norepinephrine
is released from nerve endings, and it activates β 1 adrenoreceptors located on renin-
containing juxtaglomerular granular cells and α 1 receptors on the basolateral mem-
brane of renal tubular epithelial cells in the proximal tubule and on the vascular
smooth muscle cells of the intrarenal resistance vasculature. These receptor activa-
tions result in enhanced renin secretion (with subsequent RAS stimulation),
increased renal tubular sodium reabsorption and renal vasoconstriction, reduced
renal blood flow, and decreased glomerular filtration rate [ 5 ].
Afferent fibers are located in almost every part of human kidney, however at the
highest density in renal pelvis. These fibers project to brain regions involved in
cardiovascular control: the subfornical organs, the brainstem, and the hypothalamus
[ 5 ]. Messages concerning hydrostatic pressure in renal pelvis are transmitted by
mechanoreceptors. It was shown that afferent fibers are activated in response to
pelvic wall tension increase. The afferent sensory nerves are stimulated also by
chemoreceptors responding to ischemia and chemical changes in kidney intersti-
tium. Probably, from the clinician point of view, the important factor causing sym-
pathetic afferent sensory nerve stimulation in CKD patients is kidney ischemia.
Experimental studies have shown that in rats, acute ischemia caused by renal artery
stenosis activates SNS. Rise in blood pressure was abolished in these animals after
renal denervation of stenotic kidneys. Another data indicate that in two-kidney, one-
clip hypertension in rat, denervation is associated with decrease of SNS activity. In
clinical study, it was shown that SNS activity is higher in patients with renovascular
hypertension. It was also shown that renal blood flow increase as a result of success-
ful angioplasty normalizes MSNA. Above-quoted results of both experimental and
clinical studies suggest that afferent activation affects SNS centers in central ner-
vous system and thereby increases central SNS activity and can cause
hypertension.
As it was discussed above, SNS overactivity is present in CKD patients even
with normal kidney function. However, magnitude of SNS activity increases with
the CKD progression. Grassi et al. showed that the intensity of the SNS overactiva-
tion is inversely related to the glomerular filtration rate and parallels the severity of
CKD [ 3 ].
What are the consequences of SNS overactivity in CKD patients? There are
some lines of evidence that SNS overactivity may contribute to the pathogenesis of
cardiovascular morbidity and mortality in these patients. Penne et al. assessed
MSNA in 66 CKD stage 3–4 patients and followed them for 7 years. They showed
that MSNA was significantly associated with the composite of all-cause mortality
and nonfatal cardiovascular events [ 6 ].
Zoccali et al. studied the activity of SNS estimated by plasma norepinephrine
concentration in 228 patients undergoing regular hemodialysis treatment for at least
6 months. During the 34 ± 15 months follow-up period, the cardiovascular events
such as angina episodes documented with ECG, myocardial infarction, arrhythmia,
or stroke were recorded. Plasma NE concentration was above the normal range in
45% of patients. It was also shown in this study that overactivity of SNS was associ-
ated with the number of fatal and nonfatal cardiovascular events [ 7 ]. In a study of
19 Devices for Neural Modulation (Renal Denervation, Barostimulation)