Published: May 18, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

Action Points

Catheter-based renal nerve ablation helps lower resistant hypertension, but now researchers have found that it works as well in those with chronic kidney disease (CKD), a pilot study showed.

In 15 patients with resistant hypertension and stage 3 and 4 CKD, bilateral renal denervation lowered blood pressure by a mean of 34/14 mmHg at 1 month and 32/15 mmHg at 6 months, reported Markus Schlaich, MD, of the Baker IDI Heart & Diabetes Institute in Melbourne, Australia, and colleagues.

The mean estimated glomerular filtration rate (eGFR) did not change after the procedure, even though patients received contrast media for renal catheterization or CO₂ angiography, according to the study published online in the Journal of the American Society of Nephrology.

Ablating renal nerves via the renal arteries by scarring the tissue with radiofrequency energy reduces sympathetic nerve activity, which then reduces blood pressure.

However, sympathetic nerve activation is also associated with the progression of chronic kidney disease and adverse cardiovascular outcomes, Schlaich and colleagues said.

Consequently, renal denervation performed to lower blood pressure might also have beneficial effects for kidney disease, they suggested.

Previous studies of renal denervation to reduce resistant hypertension included patients with an eGFR greater than 45 mL/min per 1.73 m². In the current study, the mean eGFR was 31 mL/min per 1.73 m².

The mean age of patients was 61 and three-quarters had diabetes. Patients were on a mean of 5.6 antihypertensive drugs, and the average systolic office blood pressure was 174 mmHg. The cohort of 15 patients comprised six women and the mean body mass index was 33 kg/m².

For the procedure, patients received an average of 9.9 ablations. In six patients, CO₂angiography was used along with a decreased volume of contrast media. The average volume of contrast in these patients was 46.7 mL compared with 82.5 mL in patients who did not receive CO₂ angiography.

After the renal denervation procedure, Schlaich and colleagues found no significant differences in kidney function compared with baseline.

There were no differences according to serum creatinine or cystatin C levels and according to plasma creatinine, cystatin C, or urea levels, they reported.

At 3 months post procedure, the average night-time systolic blood pressure declined significantly from 154 mmHg to 140 mmHg (P=0.03). At 6 months, it remained controlled at 144 mmHg.

Diastolic pressure at 3 months also declined significantly from an average of 78 mmHg to 70 mmHg (P=0.018), and the pattern continued at 6 months as well (78 mmHg versus 75 mmHg, P=0.02).

They concluded that bilateral renal denervation in patients with moderate to severe CKD is safe and effective.

Although the study was small, researchers said that it also showed the potential for the procedure to have beneficial effects other than lowering blood pressure, including increasing hemoglobin and decreasing proteinuria, brain natriuretic peptide levels, and peripheral arterial stiffness index.

They advised against generalizing their findings to the larger population of patients with various forms of CKD. Rather, these findings can provide "guidance for further studies," they said.

This study was funded in part by grants from the National Health and Research Council of Australia and the Victoria government's Operational Infrastructure Support Program.

Schlaich reported relationships with Medtronic, Abbott Pharmaceuticals, Novartis Pharmaceuticals, Servier, and Boehringer Ingelheim. His co-authors reported relationships with Medtronic, Pfizer, and Wyeth Pharmaceuticals. One co-author is an employee of Medtronic.

From the American Heart Association:

• AHA Science News: Scientific Sessions 2010 - Symplicity HTN-2: International, Multicenter, Prospective, Randomized, Controlled Trial Of Endovascular Selective Renal Sympathetic Denervation For The Treatment Of Hypertension

Primary source:Journal of the American Society of Nephrology
Source reference:
Hering D, et al "Renal denervation in moderate to severe CKD" J Am Soc Nephrol 2012; DOI: 10.1681/ASN.2011111062.

Add Your Knowledge ™

Chris Kaiser

Cardiology Editor

Chris has written and edited for medical publications for more than 15 years. As the news editor for a United Business Media journal, he was awarded Best News Section. He has a B.A. from La Salle University and an M.A. from Villanova University. Chris is based outside of Philadelphia and is also involved with the theater as a writer, director, and occasional actor.

Related Article(s):

• ACC: Zapping Renal Nerves Cuts HTN
  
• AHA: RF Kidney Punch Knocks Down Refactory BP
  

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EDMONTON - The province needs better communications to co-ordinate wildfire fighting efforts around populated areas, says the chair of a committee that reviewed the handling of last year’s devastating Slave Lake fires.

It should also consider establishing thresholds to trigger earlier evacuation alerts, Bill Sweeney said Friday at the legislature.

Alberta Environment and Sustainable Resource Development (ESRD) must be poised to communicate quick decisions in the “new reality” created by Alberta’s longer and more volatile fire season, he said as the committee report was released.

“All of these things have to be instant. They can’t take time. In the Slave Lake situation, that was problematic,” Sweeney said.

“On May 15, when things went bad, they went bad quickly ... I think people in the community should have had more information than they did receive.”

Sweeney and wildfire behaviour specialist Dennis Quintilio, who provided technical expertise about the fire, suggested the province could look at establishing an early-alert system that warns residents to be ready to leave.

There should be “thresholds for alert,” Quintilio said.

“I think it would be straightforward to establish these thresholds, and they may be different community by community.”

The advice to revamp wildfire communications and incident-management plans came as part of 21 recommendations from the wildfire review committee, an independent group the province established last year.

The committee examined circumstances around three wildfires that burned 22,000 hectares in the Lesser Slave Lake area, including the fire discovered May 14, 2011, that destroyed more than 500 homes and businesses in the town of Slave Lake and caused about $742 million in damage.

A complex set of circumstances led to the destruction, including winds up to 100 kilometres an hour that whipped fire through an aging forest full of fast-burning wood such as black spruce trees, Quintilio said.

“This aging forest which I’ve described, it’s only getting older … and in Alberta we’re building into the forest area probably more aggressively than most,” he said.

“It just sets us up for more of these catastrophic events. So the conclusion is the 2011 fire season may well be the forerunner of future fire seasons.”

Five days of sustained 50-kilometre-an-hour to 60-kilometre-an-hour winds fanned the Slave Lake fire and showered the area with red-hot embers, Quintilio said.

“I went back (in weather records) to 1974 and could not find five consecutive days that were anywhere near that windy.”

To fight the voracious blaze, the province relied on an incident-command model that has worked well for past wildfires, but a different strategy is needed to handle fires where forested areas and urban centres meet, Sweeney said.

The province needs immediate connections to local government officials, emergency-response organizations such as police, municipal firefighting teams, hospitals, nursing homes and other groups, he said.

That is particularly important as more housing is built in forested areas, meaning fires can quickly spread into communities, he said.

“They’re happening in people’s back yards,” Sweeney said. “Our propane, our gas, our house, the mulch in our gardens, the firewood that we put under our decks — all of this is fuel that is new for fires in terms of wildland fires.”

Slave Lake Mayor Karina Pillay-Kinnee said the comprehensive wildfire review should help protect communities, particularly if communications are improved.

“Our last briefing was that the fire wasn’t going to hit our community and then all of a sudden, within an hour or half an hour, we saw the winds pick up, power went down, the radio station went down and cell service was overloaded, so it was just extraordinary that all that happened at once,” Pillay-Kinnee said.

“It was very complicated to keep communication lines open to our residents and understand what was happening on the ground.”

The municipal district of Lesser Slave River faced similar problems, Reeve Denny Garratt said.

“We have to get this information from ESRD in a timely and appropriate fashion so we can make the necessary calls to evacuate people.”

The wildfire review committee recommended the government issue fire weather advisories that warn how a fire might behave.

Government should also beef up first-response firefighting crews and have them ready to deploy earlier during fire season, with some experts working on prevention in the off-season.

The province should make smart investments in fire prevention, including by boosting participation in the already established FireSmart program that teaches people how to reduce fire hazards and protect their homes from wildfire, the report said.

Alberta Environment and Sustainable Resource Development Minister Diana McQueen said the province has already made some of the suggested changes.

That includes spending $20 million on FireSmart projects in the Slave Lake region, updating FireSmart community plans and starting the wildfire season a month earlier, on March 1, McQueen said.

As well, the province trained 100 new firefighters for duty this year.

Critics have argued emergency crews could have saved more homes and businesses with different decisions.

However, the review committee concluded provincial staff made the best decisions they could under difficult conditions, Sweeney said.

The wildfire review committee report is available on the ESRD website.

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...

Published: May 18, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

Action Points

PARIS -- More dramatic blood pressure reductions may be on the horizon for patients with resistant hypertension given the phalanx of renal denervation systems under development.

Results of pilot studies on a variety of novel renal sympathetic nerve ablation catheters are achieving in the range of 28/10 to 32/15 mm Hg blood pressure reductions at one month, researchers reported here at the EuroPCR meeting.

Clinical trials of the first such device -- the Symplicity single-electrode radiofrequency ablation device, on the market in Europe -- showed a 1-month drop in BP of 14/10 to 20/7 mm Hg in clinical trials.

"New second generation devices may be improving not only safety but also efficacy," Stephen Worthley, MBBS, PhD, of the University of Adelaide, Australia, told MedPage Today.

Although still in the early phases of clinical study, stenosis or other complications to the renal artery haven't been a problem across the systems, he and several other groups reported at sessions on the percutaneous renal denervation device pipeline.

"We do see local effects but they don't seem enduring," said one session chair Robert Whitbourn, MBBS, of St. Vincent's Hospital in Melbourne, Australia. "RF seems to be very clean energy. The artery does seem robust."

Nerves are more sensitive than arteries to damage from high temperatures, explained another moderator, Ron Waksman, MD, of Washington Hospital Center in Washington, D.C.

Arteries, too, vary in their tolerance, with the renal artery apparently able to handle damage better than the pulmonary artery, for example, he added.

Multi- or Large-Electrode Systems

First-in-man trial results with the four-electrode EnligHTN radiofrequency ablation device showed no serious complications related to the device or the procedure, such as renal artery dissection, aneurysm, stenosis, or flow-limiting vasospasm.

The 46 resistant hypertension patients treated did have some minor procedural events, including four cases of hematoma, three vasovagal responses at sheath removal, and two cases of post-procedural transient bradycardia.

Renal function didn't appear affected at one month.

But office-measured blood pressure dropped by an average 28/10 mm Hg from a mean of 176/96 at baseline to 148/87 at 1 month (P<0.0001), Worthley reported.

Altogether, 78% of the patients were considered responders with at least a 10 mm Hg systolic reduction, and 41% got down to the goal of 140 mm Hg.

Another device with eight electrodes on a balloon catheter gave similar results in the first 10 patients reported by Raymond Cohen, CEO of device maker Vessix Vascular, in the REDUCE-HTN study.

No complications were seen, but 1-month blood pressure fell by 30/11 mm Hg, with all patients being responders.

Another design strategy is a spiral electrode around the catheter head to provide multiple ablations at once.

Preclinical results reported with the OneShot system showed effective ablation of renal nerves and an 84% reduction in renal norepinephrine content compared with controls, which would limit the sympathetic activation that raises blood pressure.

RF Alternatives

But not all the devices are sticking with radiofrequency ablation, generating elevated temperatures with other strategies instead.

The Paradise system, for example, uses an ultrasound catheter to heat circumferentially at a depth while cooling the endothelium of the vessel it is in direct contact with.

In the pilot REDUCE trial with that novel strategy, no serious device-related adverse events occurred among the 15 treated patients, although there was one artery dissection from the catheter sheath.

Office-measured blood pressure fell by an average 30/14 mm Hg at 1 month and was 32/16 below baseline at 3 months, Raoul Bonan, MD, of the Montreal Heart Institute in Canada, reported at the conference.

Two other groups reported on strategies without clinical experience yet:

• One using nanomagnetic particles attached to Botox B as a neurotoxin that are injected into the renal artery and then manipulated with an external magnet
• Another using a balloon catheter with holes to push the cancer drug vincristine (Oncovin, Vincasar) into the renal arterial wall where it has a neurotoxic effect

Cautions for the Field

Despite the promise of renal denervation for treating a difficult condition -- by definition persistent hypertension despite treatment with three or more antihypertensives, including a diuretic -- experts in the field urged a careful path for clinical practice and research alike.

The alteration in the renal artery is irreversible, Jean Renkin, MD, of St. Luc University Hospital in Brussels, Belgium, noted at the conference's "great debate" session.

"One of the main messages will be proper selection of patients for this procedure," he said.

That's key because patients are going to be driving demand for renal denervation, noted nephrologist William McKane, MB, of the Sheffield Kidney Institute in Sheffield, England.

"You're going to have patients knocking on your door asking for this treatment," he told attendees. "It's important to understand what we know but also what we don't know."

Some of those questions are how the treatments compare with sham control, which none of the studies yet have used, and what the long term outcomes will be with the denervation procedure.

Renal nerves can regrow, although data from the Symplicity trials suggest a durable effect over at least 3 years.

Also, the epidemiologic data projecting the effect of a particular blood pressure difference on mortality and other outcomes hasn't panned out quite as well in interventional trials, McKane cautioned.

Another concern is that renal artery stenosis may develop slowly, taking up to a decade to show up after radiation, he added.

The Symplicity trial excluded patients with even moderate or more advanced kidney disease and its quality of surveillance for complications wasn't compelling, McKane argued.

"It's too early to tell what the impact on GFR [glomerular filtration rate] is really going to be," he said.

For the time being, it's important to reserve renal denervation procedures to only good renal teams with representation by hypertension specialists, radiologists, and nephrologists that can carefully screen patients for truly medication-resistant hypertension, Renkin suggested.

"We need to be very careful that we do not kill a promising technology with incorrect patient selection," agreed Pierre-Francois Plouin, MD, of the Hospital Europeen Georges Pompidou in Paris, and a past president of the French Society of Hypertension.

The EnligHTN trial was supported by St. Jude Medical.

Worthley reported having no conflicts of interest to disclose.

The REDUCE-HTN trial was supported by Vessix Vascular.

Cohen reported being CEO of Vessix Vascular.

The Paradise renal denervation device study was supported by ReCor Medical.

Bonan reported consulting and being a stockholder in ReCor Medical.

Whitbourn reported research support from Abbott Vascular, Boston Scientific, and Medtronic.

Waksman and Plouin reported having no conflicts of interest to disclose.

Renkin and McKane reported receiving honoraria from Medtronic.

Primary source:EuroPCR meeting
Source reference:
Worthley S, et al "Safety and efficacy of a novel multi-electrode renal denervation catheter in patients with resistant hypertension: a first-in-man multi-center study" EuroPCR 2012.

Additional source: EuroPCR meeting
Source reference:
Durand Zaleski I, et al "2012 Great debate: The interventional treatment of resistant hypertension" EuroPCR 2012.

Additional source: EuroPCR meeting
Source reference:
Grube E, et al "Cardiovascular innovation pipeline -- renal denervation" EuroPCR 2012.

Add Your Knowledge ™

Crystal Phend

Staff Writer

Crystal Phend joined MedPage Today in 2006 after roaming conference halls for publications including The Medical Post, Oncology Times, Doctor’s Guide, and the journal IDrugs. When not covering medical meetings, she writes from Silicon Valley, just south of the San Francisco fog.

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Ann Arbor resident Doug Thompson, 36, got a phone call in 2011 that changed the rest of his life.

Just days before, he went to his doctor for a routine physical and blood work. By the end of the week, his doctor told him that he was near kidney failure at just 19 percent kidney function. With such low kidney function, Thompson would either need to begin dialysis or receive a kidney transplant to stay alive.

Thompson says the initial news from his doctor was shocking.

"I didn't know much about what the kidneys do," he said. "Their main function, sure, but how important they are to your body was shocking to learn."

The hardest part about understanding his diagnosis, he said, was not actually feeling sick at first.

"I felt perfectly fine up until a point, but as the disease progressed, I became super tired all the time and had absolutely no appetite," he said.

After his diagnosis, things went downhill quickly for Thompson. In February 2012, he began hemodialysis treatments three days a week for four hours at a time. He says that hemodialysis was very challenging and demanding, often affecting his entire day.

"When I left the dialysis unit, my day was over. It took all of my energy to get home, and I had to have someone drive me," he said.

After about one month of hemodialysis, Thompson switched to peritoneal dialysis. Peritoneal dialysis requires regular exchanges throughout the day and can be managed without visiting a medical facility, but also has many risks related to having a permanent tube in the abdomen.

Despite the challenges that Thompson has faced in the last eight months, his own diagnosis has inspired him to help others. Continued...

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