Effects of renal denervation on kidney function and long-term outcomes: 3-year follow-up from the Global SYMPLICITY Registry

Abstract

AimsSeveral studies and registries have demonstrated sustained reductions in blood pressure (BP) after renal denervation (RDN). The long-term safety and efficacy after RDN in real-world patients with uncontrolled hypertension, however, remains unknown. The objective of this study was to assess the long-term safety and efficacy of RDN, including its effects on renal function.Methods and resultsThe Global SYMPLICITY Registry is a prospective, open-label registry conducted at 196 active sites worldwide in hypertensive patients receiving RDN treatment. Among 2237 patients enrolled and treated with the SYMPLICITY Flex catheter, 1742 were eligible for follow-up at 3 years. Baseline office and 24-h ambulatory systolic BP (SBP) were 166 ± 25 and 154 ± 18 mmHg, respectively. SBP reduction after RDN was sustained over 3 years, including decreases in both office (−16.5 ± 28.6 mmHg, P < 0.001) and 24-h ambulatory SBP (−8.0 ± 20.0 mmHg; P < 0.001). Twenty-one percent of patients had a baseline estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Between baseline and 3 years, renal function declined by 7.1 mL/min/1.73 m2 in patients without chronic kidney disease (CKD; eGFR ≥60 mL/min/1.73 m2; baseline eGFR 87 ± 17 mL/min/1.73 m2) and by 3.7 mL/min/1.73 m2 in patients with CKD (eGFR <60 mL/min/1.73 m2; baseline eGFR 47 ± 11 mL/min/1.73 m2). No long-term safety concerns were observed following the RDN procedure.ConclusionLong-term data from the Global SYMPLICITY Registry representing the largest available cohort of hypertensive patients receiving RDN in a real-world clinical setting demonstrate both the safety and efficacy of the procedure with significant and sustained office and ambulatory BP reductions out to 3 years.

Is There a Role for Device Therapies in Resistant Hypertension?

“…It is estimated that only about 30% of patients with RH would not qualify for aldosterone antagonist therapy on the basis of baseline low renal function (eGFR,50 ml/min) or serum potassium .4.5 mmol/L (23). Despite these estimates, guideline-concordant therapy using aldosterone antagonists is low in clinical trials and registries of RDN in RH (23%-26%) (22,(24)(25)(26). Understanding the impact of use of aldosterone antagonists on the effect of RDN is RH is essential to define the value of RDN.…”

“…Bilateral RDN is performed under 60 minutes with the administration of approximately 129678 ml of contrast (25). Among 998 procedures in the Global SYMPLICITY Registry, there were six peri-procedural complications (two renal artery dissections, three femoral artery pseudoaneurysms, and one groin hematoma) (31).…”

“…One-year follow-up of 2112 patients identified three cases of de novo renal artery stenosis (0.1%), 19 cases of 50% increase in serum creatinine (0.9%), and nine cases of progression to ESKD (0.4%) (25). Extended follow-up to 3 years (N51345) revealed a total of four cases of renal artery stenosis (0.3%), 24 cases of increased serum creatinine (2%), and 23 cases of ESKD (2%) (25). Fifty nine (4%) patients died after 3 years, 29 of which were due to cardiovascular causes.…”

Effects of sympathetic modulation in metabolic disease

“…11 However, longer term follow-up data are thus far only available for up to 3 years from SYMPLICITY HTN-1, 18 SYMPLIC-ITY HTN-2, 92 and from the Global SYMPLICITY Registry. 93 This is mainly due to the fact that follow up was only planned for 3 years following the procedure. Although safety of the procedure was demonstrated in all these studies, longer term follow-up data together with reporting of cardiovascular and renal endpoints would be useful.…”

Renal Sympathetic Nerve-Derived Signaling in Acute and Chronic Kidney Diseases

“…We reported that RDNx prevented the development of tubulointerstitial fibrogenesis and inflammation after unilateral ureteral obstruction (UUO) and kidney ischemia/reperfusion injury (IRI) independent of BP changes [25,31]. In addition, RDNx did not worsen kidney function of patients and renal injured mice-as assessed by glomerular filtration rate (GFR), plasma creatinine, cystatin C, or urea levels, and tubular morphological damages-indicating that it is safe even when CKD is present [25,[31][32][33]. Here, we review the progress in our understanding of the molecular mechanisms of NE and ARs signaling in AKI, AKI to CKD transition and CKD.…”