From a single-center prospective registry including 318 patients with resistant hypertension referred for RDN between July 2011 and April 2015, we included for the purpose of the present study 31 patients with complete information on blood pressure (BP) measurements (both office and 24-h ambulatory blood pressure monitoring [ABPM]) at baseline and 12 months, transthoracic echocardiogram and renal function (creatinine clearance and ACR), out of 65 patients who were considered good candidates and underwent RDN (Figure 1).

Figure 1.

Flowchart of patient selection. Of the total number of patients observed in an outpatient hypertension clinic (n=318), 253 were excluded for various reasons (see main text) and 65 underwent renal denervation. Of these 65, complete 12-month follow-up with ambulatory blood pressure monitoring and transthoracic echocardiographic data were available in 31 patients. ABPM: 24-h ambulatory blood pressure monitoring; ACR: albumin-to-creatinine ratio; BP: blood pressure; eGFR: estimated glomerular filtration rate; RDN: renal denervation.

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The details of this patient population have been previously described.11,14 Briefly, all patients who underwent RDN were aged over 18 years, with persistent office systolic blood pressure (SBP) above 160 mmHg even after optimal antihypertensive therapy (at least three drugs, including a diuretic). Before RDN all patients were studied for secondary causes of hypertension and visited regularly (for at least six weeks) in order to ensure drug regime optimization and full compliance with medical treatment.

Demographic, clinical, anthropometric, laboratory and procedural data were recorded and stored in a dedicated database and written informed consent was obtained from all patients. The study was approved by the ethics committee of Hospital de Santa Cruz and Nova Medical School, Lisbon, Portugal.

Office BP readings were measured in a seated position, after a 5 min rest (in accordance with the European guidelines for the management of arterial hypertension), using an Omron HEM-907 semiautomatic oscillometric sphygmomanometer (Omron Healthcare, USA).

At baseline, before RDN, BP measurements were taken in both arms and the arm with the higher BP was selected for all subsequent readings. The mean of three measurements was used for analysis. An ABM monitor (Spacelabs Healthcare, USA) was used for 24-h ABPM assessment.

Patients with a decrease of 10 mmHg or more in office SBP or of 2 mmHg or more in 24-h ABPM SBP at 12-month follow-up were considered to be BP responders to RDN.11,15

Creatinine clearance was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Albuminuria was obtained in spot urine and measured using the ACR, expressed in mg/g, which is equivalent to 24-h albumin excretion in mg/day. ACR values were acquired before RDN (at baseline) and at 12-month follow-up.

RDN procedures were performed using mild anesthesia (propofol and remifentanil) for sedation and pain control. An activated clotting time of 250-300 s was obtained with unfractionated heparin. After femoral artery access, abdominal aortography and selective renal artery angiography were performed to confirm anatomic eligibility. In all cases, the femoral access site was closed using a sealing device (Angio-Seal®, St. Jude Medical, USA).

Denervation was performed using the following radiofrequency systems: Symplicity® (n=25), EnligHTN® (n=4) and OneShot® (n=2), in accordance with standard techniques.

Continuous variables are reported as mean ± standard deviation. Normality was tested with the Kolmogorov-Smirnov test and/or visual assessment of a Q-Q plot. Normally distributed variables were compared between baseline and 12-month follow-up using a paired Student's t test, or a Wilcoxon matched-pairs test if not normally distributed. Discrete variables are expressed as frequencies and percentages. Statistical comparisons of characteristics at baseline and at follow-up were performed using the chi-square test or Fisher's exact test, as appropriate, for categorical variables and the paired Student's t test for continuous variables. A two-tailed p value <0.05 was considered as statistically significant.

SPSS® version 21.0 (IBM SPSS Inc, Chicago, IL) was used for data processing and statistical analysis.

A total of 318 patients were observed in an outpatient hypertension clinic between 2011 and 2015. Of these, 253 were excluded due to: (a) BP control being achieved after dose and/or drug changes (n=139); (b) a secondary cause of hypertension (n=31); (c) renal anatomy considered unsuitable for RDN on computed tomography angiography; (d) estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2; (e) patient refusal after discussion of the expected benefits and risks. A total of 65 patients were considered good candidates and underwent RDN. Of these, the first 31 with complete data on blood and urine samples, office BP and 24-h ABPM, and transthoracic echocardiogram at both baseline and 12-month follow-up were included in the present analysis (Figure 1). Data on left ventricular mass and function have been reported elsewhere.11

Mean age was 65±7 years, all patients were Caucasian and 48% (n=14) were male. Regarding cardiovascular risk factors, 71% had type 2 diabetes, 68% were obese (mean body mass index 32±6 kg/m2), 68% had dyslipidemia and only one patient was an active smoker. Ten patients (33%) had manifestations of vascular disease (mainly coronary artery disease). Mean eGFR was 76.4±24.7 ml/min/1.73 m2 and five patients had chronic kidney disease (eGFR <60 ml/min/1.73 m2) (Table 1). At baseline, median ACR was 25.8 (interquartile range [IQR] 9.0-574.0) and 15 (48%) patients had ACR >30 mg/g.

Most patients (90%) had known hypertension for at least 10 years and were treated at baseline with a mean of 5.8 anti-hypertensive drugs, corresponding to a mean of 5.5 different drug classes. Of note, 74% were treated with spironolactone. Details on antihypertensive medication at baseline and follow-up are presented in Table 2.

Mean office SBP and diastolic BP (DBP) at baseline were 176±24 mmHg and 90±14 mmHg, respectively, and mean heart rate was 73±11 bpm. On 24-h ABPM, mean SBP and DBP were 150±20 mmHg and 83±10 mmHg, respectively (Table 3).

At 12-month follow-up mean SBP had decreased from 176±24 to 149±13 mmHg (p<0.001) and DBP from 90±14 to 79±11 mmHg (p<0.001). These changes were consistent with the results of 24-h ABPM, in which mean SBP decreased from 150±20 to 132±14 mmHg (p<0.001) and mean DBP from 83±10 to 74±9 mmHg (p=0.001). At 12-month follow-up, 71% of patients were considered office SBP responders and 84% were considered ABPM SBP responders (Table 3). During this period there was also a reduction in the number of antihypertensive drugs and classes taken; the number of drugs decreased from 5.8±1.1 to 5.0±1.2 (p=0.002) and drug classes from 5.5±0.9 to 4.9±1.1 (p=0.02) (Table 2).

At baseline, median ACR was 25.8 mg/g (IQR 9.0-574.0 mg/g) and 48.4% of patients (n=15) had an ACR >30 mg/g. We found a significant reduction at 12-month follow-up to a median of 14.8 mg/g (IQR 4.5-61.0 mg/g, p=0.007) (Table 3).

Interestingly, we also found a significant reduction in the percentage of patients with ACR >30 mg/g between baseline and 12-month follow-up (Figure 2). Considering patients with any ACR reduction as ACR responders, 77.4% (n=24) of patients were ACR responders. The distribution of patients across the different classes of urinary albumin excretion also demonstrated a favorable effect (Figure 3).

Figure 2.

Values of albumin-to-creatinine ratio and estimated glomerular filtration rate at 12 months after renal denervation. There was a significant reduction in the median values of ACR and the percentage of patients with ACR >30 mg/g, without significant changes in eGFR. ACR: albumin-to-creatinine ratio; eGFR: estimated glomerular filtration rate.

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Figure 3.

Percentages of patients in the different albumin-to-creatinine ratio subgroups. There was a numerical decrease in the percentage of patients with an ACR >300 mg/g and an increase in patients with normal urinary albumin excretion between baseline and 12-month follow-up. ACR: albumin-to-creatinine ratio.

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When the results were split according to ABPM SBP responder status, we found a significant reduction in responders (from 25.6 mg/g [IQR 8.7-382.8 mg/g] to 15.9 mg/g [IQR 4.4-55.0 mg/g], p=0.009), and a numerical decrease in non-responders (from 165.0 mg/g [IQR 8.8-1423.5 mg/g] to 13.6 mg/dl [IQR 5.7-1417.0 mg/g], p=0.345), probably due to the small number of patients in this subgroup (Table 3 and Figure 4). The same analysis was performed according to dipper status and the results were similar, with a significant reduction in patients with dipper status on baseline ABPM (Table 3 and Figure 5).

Figure 4.

Values of albumin-to-creatinine ratio at 12 months after renal denervation in 24-h ambulatory blood pressure monitoring responder subgroups. There was a significant reduction in median ACR in the BP responder subgroup, and a numerical decrease in non-responders. ACR: albumin-to-creatinine ratio; BP: blood pressure.

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Figure 5.

Values of albumin-to-creatinine ratio at 12 months after renal denervation according to dipper status on 24-h ambulatory blood pressure monitoring. There was a significant reduction in median ACR in the dipper subgroup, and a numerical decrease in non-dippers. ACR: albumin-to-creatinine ratio.

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With regard to diabetic status, patients with diabetes had a higher median baseline ACR and showed a statistically significant decrease (from 48.9 mg/g [IQR 9.1-1116.3 mg/g] to 23.1 mg/g [IQR 4.3-123.8 mg/g], p=0.028); there was also a numerical decrease in ACR in non-diabetic patients (from 25.4 mg/g (IQR 5.3-68.6 mg/g) to 10.9 mg/dl (IQR 3.4-20.8 mg/g), p=0.066), probably also due to the small patient sample in this subgroup (n=9) (Table 3 and Figure 6).

Figure 6.

Values of albumin-to-creatinine ratio at 12 months after renal denervation according to diabetic status. There was a significant reduction in median ACR in patients with diabetes, and a numerical decrease in the smaller subgroup of patients without diabetes. ACR: albumin-to-creatinine ratio.

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There were four vascular access complications: three hematomas and one femoral pseudoaneurysm. No significant changes in eGFR were seen (Table 3 and Figure 2).

The authors declare that no experiments were performed on humans or animals for this study.

The authors declare that no patient data appear in this article.

The authors declare that no patient data appear in this article.