Nierdenervatie als behandeling van hoge bloeddruk na niertransplantatie.

Rationale:

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.



Objective:

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



Study design:

We propose a randomized controlled clinical trial (intervention group n=20; controls n=20). Intervention and control groups will receive standard protocolized antihypertensive treatment prior to, and during the trial. The intervention group will receive renal denervation in addition to standard treatment.



Study population:

Inclusion criteria are a renal allograft in situ since > 6 months with an estimated GFR >35 ml/min/ 1,73m2 and a diuresis > 200ml/day of the native kidneys at time of transplantation (to ensure presence of vital neuro-hormonally active kidney tissue) and a daytime blood pressure >140/90 mmHg (assessed by 24-hours ambulatory measurement) while on >3 antihypertensive medications in maximal tolerated dose, including a diuretic.



Intervention:

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 and patients receive standard measures for prevention of contrast nephropathy.



Main study parameters/endpoints:

Primary endpoint is blood pressure reduction after 6 months (day time blood pressure assessed by 24-hours ambulatory measurement). Secondary outcomes include changes in renal sympathetic innervation (by 123I-MIBG scintigraphy), systemic sympathetho-humoral activity (by peroneal microneurography and plasma catecholamines and rennin and aldosterone activity), eGFR, proteinuria, number of anti-hypertensive drugs needed and quality of life and adverse events.

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.

Primary and secondary measurement: At inclusion and after 6 months.

Catheter based renal denervation of the native kidneys (Symplicity system, Medtronic). Renal nerve ablation is achieved in a single 40 minute catheterisatioin session.

The control group will receive care as usual.