Catheterbased REnal SympatheCtomy for hypErteNsion after kidneyTranplantation

In patients with a renal allograft, hypertension is a major etiological factor
for cardiovascular morbidity, mortality and allograft nephropathy. Controlling
hypertension in patients with a renal allograft is therefore crucial. There is
a pressing, yet currently unmet clinical need for new blood pressure lowering
strategies in renal allograft recipients. The diseased native kidneys are major
contributors to hypertension, through neuro-hormonal up-regulation that leads
to high levels of renin and sympathetic activity. Recently a catheter-based
approach has been developed to disrupt renal sympathetic nerves. Currently this
innovative technique has only been tested to lower blood pressure in therapy
resistant hypertensive patients without significant renal disease. We
hypothesize that catheter based selective renal denervation of the native
kidneys in renal transplant recipients will improve blood pressure control and
diminish the number of antihypertensive drugs.

To test the efficacy of renal sympathetic denervation therapy with a special
focus on preservation of renal allograft function.

We propose a an intervention study with n=20 renal transplant recipients. All
patients will receive renal denervation in addition to standard treatment. All
patients get the standard protocolized antihypertensive treatment prior to, and
during the trial.

Prior to study-inclusion all patients will receive standard protocolized
hypertension treatment based on the National Kidney Foundation Kidney Disease
Quality Outcomes Quality Initiative guidelines (2004). Renal sympathetic
denervation is achieved by the interventional radiologist percutaneously
entering the lumen of the main renal artery of each of the native kidneys, with
a catheter connected to a radiofrequency generator. He applies 6-8
radiofrequency ablations within each renal artery. The procedure is performed
in an outpatient clinic setting.

- The risks of femoral artery catheterisation are bleeding, infection and
contrast-agent induced nephropathy. - The risk of the venous canulation (for
the 123I-MIBG scintigraphy, and for drawing blood) is haematoma formation, and
infection. - The direct burden of the ablation procedure is that it causes
visceral pain (from the local heat of the radiofrequency probe) that will be
treated with appropriate analgesics.
The benefits of renal denervation are an expected lowering of blood pressure
and thereby improved graft survival and cardiovascular co-morbidity risk and a
reduction in the number of anti-hypertensives needed. - The total amount of
radio-contrast agent administered during the catheterisation is < 100 ml. The
risk of contrast induced (allograft) nephropathy is minimized by pre- and
post-hydration. - Time burden: patients with a kidney transplant attend their
nephrologist on average 4 times a year. The number of extra (outpatient) clinic
visits for participation in this study is 10: o 5 of 30 minutes: outpatient
clinic visits and 123I-MIBG scanning of 2,5 hours: peroneal microneurography
and o 1 of 8 hours: for denervation procedure with pre and post-hydration. -
There are no known risks to the extra (ambulatory) blood pressure measurements.
- The total amount of blood taken in addition to standard care amounts to 70
ml. - The total radiation exposure for patients in the intervention group due
to 123I-MIBG amounts to 2 * 5,1 mSv and due to the ablation procedure to an
estimated 7 mSv. The complete radiation exposure amounts to 17 mSv. - The risk
from the microneurography is the occurrence of temporary minor paresthesias at
the site of probing in the weeks after the study [25]. This risk is thought to
be very low (< 1 %). This risk is considered acceptable given the valuable data
that this technique provides that can not be acquired otherwise. From the
introduction it is evident that the risks and burden for the patients are in
proportion to the potential value of the research and the benefit that the
patients may have.