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and DBP of 17 mmHg 3 months after RDN done with this system. In the TIVUS
(therapeutic intravascular ultrasound) system, the ultrasound beam, delivered by the
ultrasonic wave generator, does not contact arterial wall directly and remote thermal
energy delivery to the adventitia of arteries sparing intimal arteries layers. This sys-
tem offers self-regulating safety technology that monitors local tissue temperature
that prevents overtreatment if blood temperature becomes excessively elevated. In
the TIVUS-I study, in 17 patients, SBP reduction of 26 mmHg and DBP reduction
of 10 mmHg 3 months after treatment with the TIVUS system was found.
Another method of RDN relies on renal sympathetic nerve injury caused by neu-
rotoxins. For this purpose, the Bullfrog microinfusion catheters with microneedle
and protective balloon system was designed. The needle penetrates vessel wall and
delivery sympatholytic neurotoxin guanethidine in the perivascular area of nearby
SNS fibers causing nerve degeneration. Another proposed chemical agent for nerve
injury is the alkaloid vincristine. These approaches so far were used in experimental
studies only.
Currently under investigation, it is also the methods of noninvasive RDN. This
method uses low-intensity focused ultrasound that avoids many of the challenges of
invasive endovascular intervention. Kona Medical developed such a noninvasive
method of external focused ultrasound aimed to destroy renal SNS nerves. The pre-
liminary results of WAVE III study used noninvasive RDN with such a system
showed in 22 patients with resistant hypertension a SBP reduction of 20 mmHg and
DBP reduction of 6 mmHg at 3 months after procedure.
Renal Denervation in CKD
Taking into account the pathophysiological evidence described above (i.e., SNS
overactivity in CKD and the role of renal SNS nerves in pathogenesis of hyperten-
sion), the use of RDN in the treatment of CKD patients may be proposed. The aim
of RDN in CKD patients may be both renoprotection (measured by reduction of
GFR decline and proteinuria lowering) and improved blood pressure control.
In experimental studies, the renoprotective effect of renal denervation has been
showed. In Dahl salt-sensitive hypertensive rats after nephrectomy, RDN is associ-
ated with local inhibition of SNS within the kidney and prevention of glomerular
sclerosis. In rats with aortic regurgitation (as a model of chronic heart failure), RDN
and olmesartan lead to decrease of albuminuria and limit podocyte injury. In rats
after 5/6 nephrectomy after dorsal rhizotomy, the reduction of creatinine serum con-
centration, blood pressure decrease, and less glomerulosclerosis was found. In
another experimental study, it was shown that dorsal rhizotomy in rats after 5/6
nephrectomy also reduces albuminuria.
So far, in most of clinical studies evaluating RDN, CKD was an exclusion crite-
rium. However, some data concerning the influence of RDN on kidney function
comes from the studies involving hypertensive patients without overt kidney dis-
ease. Symplicity HTN-1 and HTN-2 trials revealed that renal function after RDN
M. Adamczak et al.