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Sympathetic Nervous System
Increased SNS activity is an important volume-independent cause in pathophysiol-
ogy of hypertension in CKD patients. As the kidney is not only a part of excretory
system but also a sensory organ, it is richly innervated with sensory and afferent
nerves. In addition to being the target of SNS, the kidney may also be the origin and
modulator of this activity. It is well established that renal denervation improves
resistant hypertension in general population indicating the effect of renal sympa-
thetic nerves on the pathogenesis of hypertension [ 26 ]. SNS hyperactivity leads to
arterial blood pressure elevation and triggers arterial damage.
Increased SNS activity has been demonstrated in CKD patients [ 27 , 28 ]. SNS
overactivity is also a feature of renovascular hypertension. Although the underlying
mechanisms of increased SNS activity are unclear, this overactivity in CKD may be
caused by neurohormonal mechanisms arising from kidney damage. Chronic renal
nerve activation stimulates renin along with its effects to modulate renal blood flow
and tubular function. SNS has a modulatory role rather than primary role in the
regulation of renin. Some studies have shown that plasma catecholamine levels are
consistently increased in patients with end-stage renal disease (ESRD) [ 28 ].
Ischemic injury of kidney increases the activity of SNS. Furthermore, ischemic
metabolites or uremic toxins may stimulate afferent nervous input to the central
nervous system.
In addition to its direct pressor effect, it is possible that the activation of the
RAAS may contribute to hypertension in CKD by stimulating the sympathetic ner-
vous system. Moreover, locally released angiotensin II appears to mediate central
activation of SNS activity [ 29 ]. Supporting this hypothesis, angiotensin-converting
enzyme inhibition also reduces the SNS overactivity.
Patients with CKD also have inappropriately increased sympathetic activity for
their effective volume status. Increased renal sympathetic nerve activity enhances
the reabsorption of sodium chloride and fluid by the renal tubules, as well as the
release of renin from the juxtaglomerular apparatus.
Other Humoral Factors
Manifold other humoral factors have been reported to contribute to elevation of
blood pressure in CKD. The release of vasoconstrictors (thromboxane or endothe-
lin) or deficiencies in the generation of vasorelaxant factors (nitric oxide, prosta-
glandins) at the level of the vascular endothelial cell may also participate in the
elevation of blood pressure in CKD patients [ 30 ]. The increased levels of vasocon-
strictor substances increasing peripheral resistance can be another predominant
pathophysiologic factor in CKD-related hypertension. Imbalance between vasodila-
tor and vasoconstrictor prostaglandins is also implicated in the pathogenesis of
CKD-related hypertension [ 31 ].
F. Turgut et al.