Renal Denervation Found Safe and Effective for Chronic Kidney Disease Patients

Renal denervation—a technique that uses radiofrequency waves to disrupt the overactive sympathetic nerves running along the arteries in the kidneys—can lower blood pressure in individuals with resistant hypertension and normal kidney function, but clinicians have worried that the procedure might not be safe for patients with compromised kidney function.

New research largely puts these concerns to rest. A study recently published in the Journal of the American Society of Nephrology found that renal denervation not only can safely and effectively lower blood pressure in patients with chronic kidney disease (CKD) and hypertension but also may provide additional benefits, including a potential increase in hemoglobin concentration and reductions in proteinuria, brain natriuretic peptide levels, and peripheral arterial stiffness index.

Although the study’s clinical trial enrolled only a small number of patients, making the results too limited to apply to patients with various forms of chronic renal failure, it provides guidance for further studies and clinical trials to properly assess the short- and long-term safety and efficacy of renal nerve ablation in CKD.

“It also emphasizes the concept that renal denervation may address crucial pathophysiologic mechanisms underlying the high cardiovascular morbidity and mortality rates in patients with chronic kidney disease and may provide a valuable tool in slowing the rate of progression of chronic kidney disease and its complications,” the authors wrote.

Targeting the fight-or-flight response

Overactivity of neurons in the sympathetic nervous system, which controls the body’s fight-or-flight response, is very common in patients with CKD. In addition to contributing to high blood pressure and heart problems in these patients, it can also worsen their kidney disease. Because targeting this system might provide significant benefits to individuals with kidney dysfunction, principal investigator Markus Schlaich, MD, of the Baker IDI Heart and Diabetes Institute in Melbourne, Australia, and his team designed a catheter-based renal nerve ablation trial in 15 patients with resistant hypertension and stage 3–4 CKD (mean estimated GFR 31 mL/min per 1.73 m2).

“The main aim of this study was to prove the safety and efficacy of the procedure in the setting of chronic kidney disease, which has not been tested before,” said Schlaich. Patients underwent an average of 9.9 ablation treatments, with no periprocedural or postprocedural complications.

The study participants’ average blood pressure at the start of the trial was 174/91 mm Hg even though they were taking numerous antihypertensive drugs. Their ambulatory blood pressure readings dropped considerably at 1, 3, 6, and 12 months after bilateral renal denervation (−34/−14, −25/−11, −32/−15, and −33/−19 mm Hg, respectively). Also, significant reductions in rate of blood pressure increase, blood pressure power surge, and night-to-day blood pressure ratios were observed. Moreover, renal denervation diminished mean and maximum nighttime blood pressures and restored a physiologic dipping pattern.

Peripheral arterial stiffness assessed by augmentation index was significantly reduced 3 months after the procedure (51.3 percent at baseline versus 38.7 percent at follow-up). Renal denervation did not worsen patients’ kidney function—as assessed by an estimation of GFR according to serum creatinine or cystatin C levels and according to plasma creatinine, cystatin C, or urea levels—indicating that it is safe even when CKD is present.

“So far, renal denervation has only been applied in patients with reasonably well kidney function; the present study provides first results indicating that it can also be performed in patients with more advanced kidney failure,” said Peter Blankestijn, MD, PhD, who was not involved with the work and is a nephrologist at the University Medical Center Utrecht in the Netherlands. “This is important new information, because this treatment could be very meaningful in kidney failure patients. More studies are needed,” he added. Blankestijn has researched and written about the potential of renal denervation.

Future studies

This first clinical experience with catheter-based renal nerve ablation in high-risk patients with moderate to severe kidney impairment indicates that the procedure may provide beneficial health effects beyond improved blood pressure control in patients with comorbid conditions, including resistant hypertension, diabetes, obesity, and obstructive sleep apnea.

Several interesting observations may deserve further investigation in future clinical trials. For example, the investigators noticed a tendency toward gradually increased serum hemoglobin levels in all treated patients. This could be important because the prevalence of anemia increases with deteriorating renal function and is related to heart complications and cerebrovascular events. Interestingly, the results of both experimental and human studies have suggested a role of renal sympathetic nerves in the regulation of erythropoiesis.

The investigators also observed a trend toward reduced urinary albumin excretion after patients underwent renal denervation, as well as a trend toward reduced plasma concentrations of circulating brain natriuretic peptide. Brain natriuretic peptide is considered an independent predictor of cardiovascular death not only in cardiorenal syndrome but also in early-stage kidney disease in the absence of heart failure.

Finally, patients in the study experienced an improvement in augmentation index. Higher augmentation index is associated with target-organ damage in patients receiving hemodialysis and with microalbuminuria in those with essential hypertension. Renal denervation may rapidly affect the peripheral vasculature through a significant reduction in arterial stiffness.

“These initial findings now open up an entirely new approach to better control blood pressure in chronic kidney disease and potentially slow down progression of the disease and reduce cardiovascular risk in these patients,” Schlaich said. “Studies are now warranted to look into this in detail.”

Notes

[1] Disclosures: This study was funded in part by grants from the National Health and Research Council of Australia (NHMRC) and the Victorian Government’s Operational Infrastructure Support Program. Professor Schlaich, Professor Esler, Dr. E. Lambert, and Dr. G. Lambert are supported by career fellowships from the NHMRC. Dr. Dagmara Hering is currently supported by a Research Fellowship from the Foundation for Polish Science KOLUMB/2010-1. Dr. Felix Mahfoud is supported by the Deutsche Hochdruckliga. Drs. Schlaich, Mahfoud, Walton, Krum, Boehm, and Esler are principal investigators in studies sponsored by Medtronic, the company that manufactures the renal denervation device, and have received consultancy/lecture fees from Medtronic.

[2] The article, entitled “Renal Denervation in Moderate to Severe CKD,” is available at http://jasn.asnjournals.org/.