Review and meta-analysis of renal artery damage following percutaneous renal denervation with radiofrequency renal artery ablation.

AIMS: We aimed to estimate the rate of renal artery adverse events following renal denervation with the most commonly applied radiofrequency catheter system based on a comprehensive review of published reports. METHODS AND RESULTS: We reviewed 50 published renal denervation (RDN) trials reporting on procedural safety including 5,769 subjects with 10,249 patient-years of follow-up. Twenty-six patients with renal artery stenosis or dissection (0.45%) were identified of whom 24 (0.41%) required renal artery stenting. The primary meta-analysis of all reports indicated a 0.20% pooled annual incidence rate of stent implantation (95% CI: 0.12 to 0.29% per year). Additional sensitivity analyses yielded consistent pooled estimates (range: 0.17 to 0.42% per year). Median time from RDN procedure to all renal intervention was 5.5 months (range: 0 to 33 months); 79% of all events occurred within one year of the procedure. A separate review of 14 clinical trials reporting on prospective follow-up imaging using either magnetic resonance imaging, computed tomography or angiography following RDN in 511 total subjects identified just 1 new significant stenosis (0.20%) after a median of 11 months post procedure (one to 36 months). CONCLUSIONS: Renal artery reintervention following renal denervation with the most commonly applied RF renal denervation system (Symplicity) is rare. Most events were identified within one year.

Comparison of renal artery, soft tissue, and nerve damage after irrigated versus nonirrigated radiofrequency ablation.

BACKGROUND: The long-term efficacy of radiofrequency ablation of renal autonomic nerves has been proven in nonrandomized studies. However, long-term safety of the renal artery (RA) is of concern. The aim of our study was to determine if cooling during radiofrequency ablation preserved the RA while allowing equivalent nerve damage. METHODS AND RESULTS: A total of 9 swine (18 RAs) were included, and allocated to irrigated radiofrequency (n=6 RAs, temperature setting: 50°C), conventional radiofrequency (n=6 RAs, nonirrigated, temperature setting: 65°C), and high-temperature radiofrequency (n=6 RAs, nonirrigated, temperature setting: 90°C) groups. RAs were harvested at 10 days, serially sectioned from proximal to distal including perirenal tissues and examined after paraffin embedding, and staining with hematoxylin-eosin and Movat pentachrome. RAs and periarterial tissue including nerves were semiquantitatively assessed and scored. A total of 660 histological sections from 18 RAs were histologically examined by light microscopy. Arterial medial injury was significantly less in the irrigated radiofrequency group (depth of medial injury, circumferential involvement, and thinning) than that in the conventional radiofrequency group (P<0.001 for circumference; P=0.003 for thinning). Severe collagen damage such as denatured collagen was also significantly less in the irrigated compared with the conventional radiofrequency group (P<0.001). Nerve damage although not statistically different between the irrigated radiofrequency group and conventional radiofrequency group (P=0.36), there was a trend toward less nerve damage in the irrigated compared with conventional. Compared to conventional radiofrequency, circumferential medial damage in highest-temperature nonirrigated radiofrequency group was significantly greater (P<0.001). CONCLUSIONS: Saline irrigation significantly reduces arterial and periarterial tissue damage during radiofrequency ablation, and there is a trend toward less nerve damage.

Endovascular brachytherapy for renal artery in-stent restenosis.

OBJECTIVE: Renal artery in-stent restenosis (RAISR) is not an infrequent occurrence and may be in part responsible for the failure of renal stents to improve clinical outcome. A variety of treatments have been used to restore patency, with mixed results. These include repeated percutaneous transluminal renal angioplasty (PTRA), repeated PTRA with bare-metal stents, and repeated PTRA with drug-eluting stents or covered stents. Endovascular brachytherapy (EVBT) has been proven effective in preventing recurrent neointimal hyperplasia in coronary bare-metal stents. This prompted our group to study the effect of EVBT on RAISR. METHODS: From 2004 to 2012, 21 patients (23 renal arteries) developed RAISR ≤ 30 months after the initial procedure and were subsequently treated with EVBT. Five patients had at least one prior PTRA for recurrent restenosis. Renal artery duplex scanning was performed as a baseline study within a few days of the EVBT and then every 6 months. All patients who had EVBT were concurrently treated by PTRA and EVBT on the basis of existing protocols. Patency of the treated stents was evaluated by Kaplan-Meier survival curves. RESULTS: The average onset of the original RAISR was 11 ± 9 months (range, 2-30 months; median, 8 months). The initial technical success of combined PTRA and EVBT was 100%. Mean follow-up was 44 ± 18 months (range, 14-84 months). Of five patients who had PTRA before EVBT, four were available for long-term follow-up. These four patients had a combined total number of five PTRAs before EVBT, with recurrent stenosis developing on average by 12 months. After EVBT, three stents were patent at 39, 48, and 65 months, and one stent restenosed at 42 months. This was the only patient in the entire series to develop restenosis after EVBT. CONCLUSIONS: This retrospective experience with a relatively small number of patients undergoing concurrent EVBT/PTRA for recurrent stenosis in stents placed to treat atherosclerotic renal artery stenosis suggests that EVBT is safe and provides long-term freedom from recurrent stenosis.

Renal denervation using focused infrared fiber lasers: a potential treatment for hypertension.

BACKGROUND AND OBJECTIVE: Renal denervation has recently become of great interest as a potential treatment for resistant hypertension. Denervation techniques using radio frequency (RF) or ultrasound energy sources have already been explored in literature. In this study, we investigate the use of lasers as a potential energy source for renal denervation. In vitro studies are performed in porcine/ovine renal arteries with focused laser beams at 980 nm, 1210 nm, and 1700 nm to study the ability to damage renal nerves without causing injury to non-target tissue structures like the endothelium. Then, a 980 nm laser catheter prototype is built and used to demonstrate in vivo renal denervation in ovine renal arteries. SUBJECTS AND METHODS: This study utilizes fiber coupled infrared lasers at 980 nm, 1210 nm, and 1700 nm. In vitro laser denervation studies at 980 nm are performed in both porcine and ovine renal arteries to study the ability of focused laser beams to damage renal nerves without injuring the endothelium. In vitro studies using lasers close to the lipid absorption lines at 1210 nm and 1700 nm are also performed in porcine renal arteries to study the possibility of selectively damaging the renal nerves by targeting the lipid myelin sheaths surrounding the nerves. Then, a laser catheter prototype is designed and built for in vivo renal denervation in ovine renal arteries using the 980 nm laser (powers ranging from 2 to 4 W, 5 seconds per exposure). Histochemical evaluations of the frozen sections are performed using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. RESULTS: Histochemical analysis of in vitro laser treatments at 980 nm in porcine and ovine renal arteries show clear evidence of laser-induced renal nerve damage without injury to the endothelium and part of the media. No evidence of selective nerve damage is observed using the 1210 nm and 1700 nm lasers with the current treatment parameters. Histochemical analysis of in vivo laser treatments in ovine renal arteries using a focused 980 nm laser show clear evidence of renal nerve damage with depths of damage extending > 1.5 mm from the artery wall. Sections with laser-induced damage to the media/adventitia at depths of > 1 mm without injury to the endothelium are also observed. CONCLUSIONS: We demonstrate the use of focused lasers as an attractive energy source for causing renal nerve damage without injury to the artery wall and thus, may have potential therapeutic applications for conditions such as resistant hypertension, where renal denervation has been shown to be a promising form of treatment.

Evaluation of effects of Extracorporeal Shock Wave Lithotripsy on renal vasculature with Doppler ultrasonography.

OBJECTIVES: In this prospective study, we aimed to demonstrate the effects of Extracorporeal Shock Wave Lithotripsy (ESWL) on renal blood flow in patients treated for renal/ ureteral stones. MATERIAL AND METHODS: The study group comprised 41 patients (26 males, 15 females, aged between 18-63 years, mean age 45 years), 23 with renal and 18 with ureteral stones, who underwent ESWL between March 2010 and January 2011. Colour Doppler ultrasonography and pulsed wave spectral analysis was performed before, 1 hour, and 7 days after ESWL to both ipsilateral and contralateral kidneys in order to measure resistive index (RI), pulsatility index (PI) and acceleration time (AT) values. RESULTS: One hour after ESWL, RI and PI values showed significant increase from pre-ESWL values in both ipsilateral and contralateral kidneys. However, no significant change was found in AT values. Seven days after ESWL, PI in both ipsilateral and contralateral kidneys and RI in contralateral kidney returned to pre-ESWL values. But, 7 days after ESWL, RI in the ipsilateral kidney did not return to pre-ESWL values, although decrease in RI values were observed. CONCLUSION: Spectral Doppler analysis can provide valuable information as a non-invasive method to assess the hemodynamic changes and renal microcirculation status in cases managed with ESWL.

[Endovascular radiofrequency denervation of renal arteries as an innovation method of treatment of refractory arterial hypertension. First experience in Russia].

Excessive activation of the sympathetic nervous system forms the basis of pathogenesis of essential arterial hypertension (AH). The present work was aimed at evaluating efficacy and safety of endovascular radiofrequency denervation of renal arteries in patients with AH refractory AH based on the initial first experience in with using this methodology in the Russian Federation. The interventions were carried out on December 14-15th, 2011 in the first five patients presenting with AH refractory to antihypertensive therapy consisting of three and more drugs in therapeutic doses, one of which was a diuretic. The selection criteria were systolic arterial pressure (SAP) ≥160 mm Hg or ≥150 mm Hg in the presence of type 2 diabetes mellitus. The obligatory conditions for selection were the preserved renal function [glomerular filtration rate (GFR) ≥45 ml/min] and the absence of the secondary form of AH. The procedure of denervation was performed in the conditions of roentgen-operating room using special Medtronic Ardian Simplicity Catheter System™. In all cases we managed to perform bilateral denervation of renal arteries with the radiofrequency effect in not less than 4 zones of each of vessels. Efficacy of each of the effect was registered with due regard for reaching certain temperature and values of impedance. The interventions were not accompanied by the development of any complications either in the area of manipulations or the site of puncture. Neither were there any complications from the side of the cardiovascular or excretory systems of the body. Diurnal monitoring of AP (DMAP) registered a significant decrease in SAP averagely from 174±12 to 145±10 mm Hg three days after the intervention. A persistent antihypertensive effect was confirmed by the DMAP findings one month after denervation - the SAP level averagely amounted to 131±6 mm Hg. Endovascular radiofrequency denervation of renal arteries is a safe and efficient method of treatment of AH resistant to multicomponent antihypertensive therapy.

[Renal artery stenosis after radiotherapy for Ewing's sarcoma]. / Radiotherapieinduzierte Nierenarterienstenose nach Behandlung eines Ewing-Sarkoms.

BACKGROUND: The fact that therapeutic irradiation can induce significant stenosis in the arteries of the head, neck, and chest, as well as in the aorta and the iliac arteries, is familiar in daily practice and well documented in the literature. By contrast, radiation-induced renal artery stenosis seems to be a less widely known complication. PATIENTS AND METHODS: The sudden onset of medically refractory arterial hypertension and coma in a 27-year-old man is reported, who had been treated at age 20 with chemotherapy and radiotherapy for Ewing's sarcoma in the lumbar region. This treatment had been performed at the hospital of Sion, Switzerland in 2001. Also, the relevant literature from 1965 to 2007 is reviewed to underscore various aspects of this problem and to demonstrate the clinical relevance of renal artery stenosis as a potential long-term sequela of radiotherapy. CONCLUSION: Radiation-induced renal artery stenosis has only rarely been described in the literature, but arterial hypertension due to radiation-induced renal artery stenosis is a serious long-term sequela that can appear at a latency of up to 20 years after treatment. The paucity of reports presumably reflects the lesser frequency of radiotherapy for retroperitoneal tumors as compared to head-and-neck cancers, as well as lower awareness of the problem due to diagnostic bias in the era before CT and MRI were in routine use: at that time, carotid artery stenosis was easy to diagnose by ultrasonography, while radiation-induced renal artery stenosis, whose real incidence may well be higher, probably often went undetected. Thus, when a patient with a history of abdominal or retroperitoneal radiotherapy unexpectedly develops intractable hypertension, radiation-induced renal artery stenosis must be included in the differential diagnosis.

Radiation-induced peripheral artery disease.

Radiation therapy is a cause of cardiovascular morbidity and mortality. This is due to the significant degree of atherosclerosis seen in the vessels in the vicinity of the area being irradiated. Radiation-induced peripheral arterial disease is increasingly being recognized as large populations of cancer patients survive longer, yet it is a problem that is often under reported. Although it has most commonly been associated with carotid artery disease, all vascular beds are prone to this form of injury. The injury is accelerated by usual risk factors for atherosclerosis. Developing a healthy lifestyle, dietary prudence and the aggressive treatment of hypertension, diabetes mellitus, and dyslipidemia should all be encouraged in this patient population. When revascularization strategies are warranted, the percutaneous approach may be superior to open surgery as technical difficulties may arise in the fibrotic, scarred tissue. Stenting with distal embolic protection devices should be considered as the treatment of choice for patients with radiation-induced carotid artery disease. Several reports also suggest good results with balloon angioplasty with or without stenting in the case of radiation-induced renal, iliac, and femoral artery disease. Lifelong antiplatelet therapy may be appropriate.

Bilateral renal artery stenosis after abdominal radiotherapy for Hodgkin's disease.

A 49-year-old woman was admitted with fatigue, dyspnoea, pretibial oedema and decreased daily urination. Seven years ago she was treated with doxorubicin, bleomycin, vinblastine and dacarbazine, alternating with mechlorethamine, vincristine, procarbazine and prednisone and 80 Gy abdominal radiotherapy for Hodgkin's disease. Two years later, malignant hypertension was diagnosed. Angiotensin-2 antagonist and beta-blocker treatment was given. After increased serum creatinine levels were determined, renal angiography was performed and total obstruction in the left renal artery and near total obstruction in the right side was observed. She was admitted to our clinic with oliguria, and acute renal failure was diagnosed. Balloon angioplasty and stent implantation was performed to the right renal artery. After a polyuric period, serum creatinine reduced to near normal levels. Angiotensin-2 antagonist treatment worsened the course in this patient. Patients with resistant hypertension occurring years after abdominal radiotherapy should be evaluated for renal artery stenosis.

Histomorphometric evaluation of (198)Au endovascular brachytherapy in a renal artery restenosis model in rabbits.

OBJECTIVE: The main mid-term complication of percutaneous transluminal angioplasty of the renal artery is restenosis, which occurs in up to 50% of patients. Although no pharmacologic agent to date has been effective in preventing restenosis, both beta-ray emitters and gamma-ray emitters used in endovascular brachytherapy have been shown to reduce coronary restenosis. The objectives of this study were to evaluate the efficacy of (198)Au endovascular brachytherapy in preventing restenosis after percutaneous transluminal renal angioplasty and to determine the radiation dose to the operator. MATERIALS AND METHODS: Twenty-one New Zealand white rabbits (10 females and 11 males) weighing an average of 3.5 kg (range, 3.2-3.8 kg) who had been fed a normal diet underwent bilateral 33% overdilatation with deendothelialization of the renal arteries. After 7 weeks, the induced renal artery stenoses were treated by percutaneous transluminal renal angioplasty. The rabbits were randomly assigned to one of three groups before receiving endovascular 25-Gy irradiation at a radial 2.0-mm depth with a 0.5 x 15 mm (198)Au wire (106 MBq). The right renal artery was irradiated in group A; the left, in group B. The rabbits in group C randomly received a right- or left-sided dummy wire. Operator exposure to radiation was measured using thermoluminescent dosimeters and ionization chambers. The rabbits were sacrificed after 3 weeks. The aorta and renal arteries were perfusion-fixed. The renal arteries were removed for histologic and histomorphometric study. RESULTS: Forty-two renal arteries were cut into a series of 4- micro m-thick slices. Five arteries were thrombosed (two in the irradiated group and three in the control group, p > 0.05). In the patent arteries (n = 37), the average neointimal area was 0.068 mm(2) (range, 0.009-0.234 mm(2)) in 15 irradiated segments (315 slices total), whereas the average neointimal area was 0.135 mm(2) (range, 0.016-0.324 mm(2)) in 22 control segments (462 slices total) (analysis of variance, p < 0.009), showing a percentage area of restenosis of 10.4% in irradiated arteries and 43.4% in non-irradiated arteries (p < 0.0003). Radiation dose per procedure to the operator was 0.034 mSv in the index finger, 0.024 mSv in the wrist, and undectable in the body. CONCLUSION: Endovascular brachytherapy with (198)Au appears to inhibit early renal artery restenosis and exposes the operator to a safe level of radiation.

[The rate of physiological fibrinolysis in the mesenteric and renal vessels of rabbits]. / Skorost' fiziologicheskogo fibrinoliza v mezenterial'nykh i pochechnykh sosudakh u krolikov.

In the rabbit vessels of a. mesenterica, total lysis of fibrin occurred within 60-90 minutes whereas in the renovascular basin the process took 30 minutes longer. This seems to be due to synthesis of a plasminogen activator.

[Radiation arteriopathies]. / Les artériopathies radiques.

Disease of the large arterial vessels is a relatively unknown complication of radiotherapy. However, it should be considered in the same manner as the other complications of irradiation when a tumour recurrence is suspected. The authors recall the experimental studies of Kirkpatrick and Konings, demonstrating the synergy between irradiation and hypercholesterolemia in the precocity and gravity of vascular complications. The different localisations reported in the literature are discussed: coronary, pulmonary, thoracic aorta, supra aortic, renal, digestive and ilio-femoral arteries. Finally, the authors underline the difficulty of diagnosis of post-radiotherapy without clinical, radiological or anatomopathological confirmation.

Postradiation renovascular hypertension.

Radiation injury to arteries can represent a significant complication of therapeutic irradiation, even when the dosage used has not been excessive as judged by approved protocols. Children in whom therapeutic abdominal irradiation has been used should be monitored indefinitely for the development of hypertension. The presence of hypertension in such children with normal blood urea nitrogen (BUN) and creatinine, and without proteinuria, should prompt investigation for a renovascular lesion. Standard bypass procedures are usually effective, although the long-term success may be compromised by continuing changes in affected vessels.

A comparison of the effects of 50 MeVd leads to be neutron and cobalt-60 irradiation of the kidneys of rhesus monkeys.

Twenty rhesus monkeys had one kidney irradiated (after undergoing unilateral nephrectomies) with one of four doses: 960 or 1080 rads of 50 MeVd leads to Be neutrons, or 2350 or 2700 rads of 60Co. Whereas animals treated with the lower dose of neutrons or 60Co are alive with relatively normal renal function, those treated with the higher dose of neutrons died of radiation nephritis. Animals treated with the higher dose of 60Co developed radiation nephritis but survived. The physiological and histopathological changes of radiation nephritis secondary to neutron irradiation are not qualitatively different from those reported for radiation nephritis secondary to photon irradiation.