Effects of Lumbar Sympathetic Blockade Renal Plasma Flow and Glomerular Filtration Rate.

With this study we will investigate the effects of lumbar sympathetic blockade
on ERPF and measured GFR and relative changes in non - invasive hemodynamics
measured before and after continuous lumbar sympathetic blockade or splanchnic
blockade in patients with clinically evaluated successful permanent blockade


Blocking renal sympathetic innervation is a potential therapy for
treatment-resistant hypertension. Renal sympathetic innervation regulates
sodium reabsorption and arterial resistance and thereby changes the effective
renal plasma flow (ERPF), glomerular filtration rate (GFR) and systemic
arterial blood pressure. Sympathetic innervation of the kidneys arise from
spinal cord neurons in the ganglia T11 to L1. The postganglionic nerves enter
the abdominal cavity and aortorenal ganglia and reach the kidneys through the
walls of the extra - and intrarenal arteries. In animal studies it is shown
that an increased sympathetic nerve activity causes a reduction in the ERPF and
sodium excretion. This was the basis of a new therapy for treatment resistant
hypertension: catheterbased renal sympathetic denervation, aiming to reduce
sympathetic nerve activity by using radio -frequent ablation to interrupt the
renal nerves that lie along the wall of the renal arteries. The intended effect
of renal denervation is a lowering of systemic blood pressure, but a large
variation in blood pressure response after renal denervation is shown. The
effects of renal denervation on renal function (ERPF and GFR) in humans are
unknown.
The renal effects of unilateral complete sympathetic blockade at the level L1
in humans have only been examined by a research group led by Solis Herruzo in
1987. Lumbar sympathetic blockade (LSB) is a technique to block postganglionic
sympathetic innervation completely by local anesthetics at the level of L1. For
the long- term effects (> 4 months) chemical neurolytic blockade with phenol or
radiofrequency thermal ablation (splanchnic blockade SpB ) is performed. This
procedure is usually carried out one-sided, and usually at the level of L1 to
L4.The study of Solis Herruzo examined the effects of LSB on creatinine
clearance and measured ERPF in a small group of 8 patients with kidney failure
due to hepatorenal syndrome. The patients showed a significant increase in ERPF
and urinary sodium excretion after LSB. The effect was greatest in patients
with an eGFR < 25ml/min at baseline.
Our study is based on these results: LSB seems to be a very suitable model to
assess the renal effects of changes in renal sympathetic innervation of the
human kidney.

An increased sympathetic nervous system causes vasoconstriction and increased
arterial blood pressure. Sympathetic activity activates the renin - angiotensin
- aldosterone - system, and leads to an increase in blood pressure. This also
increases the cardiac output and GFR and ERPF. Therefore, we will explore the
effects of LSB / SpB on ERPF and GFR and the relative changes in cardiac
output, stroke volume, systemic vascular resistance and pulse wave velocity
measured using non - invasive hemodynamic measurement with NexfinTM.

With this study we will investigate the effects of lumbar sympathetic blockade
on ERPF and measured GFR and relative changes in non - invasive hemodynamics
measured before and after continuous lumbar sympathetic blockade or splanchnic
blockade in patients with clinically evaluated successful permanent blockade

n=15 patients with an indication for lumbar sympathetic blockade or splanchnic
blockade will be included in the study. Four to six weeks before the blockade
the first measurement will be scheduled. On this day, ERPF measured with 131I
Hippuran and GFR with 125I - Iothalamate will be measured. During these
measurements, blood is collected. Prior to the study, all patients have had
diet instructions and the patient has collected 24-hour urine samples. Systemic
haemodynamics will be measured non-invasively with NexfinTM while standing and
while in supine position breathing room air, 50% oxygen and 100% oxygen. The
second measurement with identical measurements takes place 1-8 weeks after
lumbar sympathetic blockade or splanchnic blockade, provided that it that the
LSB or SpB has been successful ( in LSB signs of vasodilation in the lower
extremity, and pain reduction in case of splanchnic blockade) assessed by the
clinician.

Radiation exposure due to the GFR measurement with 125I-iothalamate and ERPF
measurement with 131I-hippuran is 0.8mSv, which is a minor risk class IIa of
the ICRP. This is approximately 32% of the yearly background radiation in The
Netherlands. Placement of an intravenous cannula causes the risk for infection
and bleeding. The amount of blood drawn is 54 ml per measurement, amounting to
108 ml in total for two study days.
Patients receive air with different oxygen concentrations to breath over a
non-rebreathing mask for 30 minutes. This has no negative effects. Only wearing
the mask may give minimal discomfort.
The time spent is 13 hours in total. There are dietary restrictions for this
study and two times 24hour-urine collections.
Patients do not have a benefit from participation nor a group related benefit.