J Nephrol DOI 10.1007/s40620-014-0059-y
CASE REPORT
Single-side renal sympathetic denervation to treat malignant refractory hypertension in a solitary kidney patient Flavio Ribichini • Angela Ferrara • Michele Pighi • Gabriele Pesarini • Alessia Gambaro • Enrico Valvo • Antonio Lupo • Corrado Vassanelli
Received: 19 August 2013 / Accepted: 22 November 2013 Ó Italian Society of Nephrology 2014
Abstract Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. Patients affected by renovascular or anatomical abnormalities have hitherto been systematically excluded from clinical trials with RSD because of concern about safety and the unknown efficacy of the procedure in this subgroup of patients. We describe the management of a case of RSD in a single-kidney patient with refractory hypertension; the patient had had a previous surgical right nephrectomy for renal cell carcinoma that subsequently required no other oncologic treatment. After multidisciplinary assessment, the patient underwent RSD. The procedure was performed through a 6F femoral access using the SymplicityTM RSD system (Medtronic, Mountain View, CA, USA). Radiofrequency was applied to the renal artery wall in 6 different points under general sedation with midazolam to control back pain caused by the procedure, that was performed without periprocedural complications. The patient was discharged 2 days later after a control of the vascular access site and routine biochemical examinations. The following 9-month follow up showed a significant reduction in blood pressure and stable renal function, without signs of renal damage. Our report confirms the feasibility of RSD in this delicate context, without evident negative effects on kidney function and with a significant reduction in blood pressure. Future studies are needed to fully clarify the value of RSD in single-kidney patients.
F. Ribichini (&) A. Ferrara M. Pighi G. Pesarini A. Gambaro E. Valvo A. Lupo C. Vassanelli Department of Medicine, University of Verona, Verona, Italy e-mail: [email protected]
Keywords Renal sympathetic denervation Refractory hypertension Solitary-kidney
Introduction Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. The safety and efficacy of this novel technique have been investigated in recent randomized controlled trials [1, 2], but patients affected by renovascular or anatomical abnormalities were systematically excluded from these clinical trials. In particular, patients having only one kidney due to congenital or post-surgical conditions have been banned from enrollment because of concern about safety and the unknown efficacy of the procedure in this subgroup of patients.
Case report A 56-year-old man with a single kidney was admitted to our Department for malignant arterial hypertension, refractory to medical therapy despite a full dose treatment with seven anti-hypertensive drugs (Table 1). The patient had undergone surgical right nephrectomy 15 years before, for renal cell carcinoma at the age of 40 years, that subsequently required no other oncologic treatment. He had also mild chronic renal failure (serum creatinine 1.5 mg/dl and estimated glomerular filtration rate (eGFR) 64 ml/min/1.73 m2) and several cardiovascular risk factors: diabetes mellitus, obesity, hypercholesterolemia and smoking. He developed arterial hypertension in 2008, and
123
J Nephrol Table 1 Changes in antihypertensive therapy after renal sympathetic denervation Pre-RSD
3 months Post-RSD
6 months Post-RSD
9 months POST-RSD
Furosemide 250 mg/die
Furosemide 250 mg/die
Furosemide 25 mg/die
Furosemide 25 mg/die
Telmisartan 120 mg/die
Telmisartan 120 mg/die
Telmisartan 120 mg/die
Telmisartan 120 mg/die
Barnidipine 20 mg/die
Barnidipine 20 mg/die
Barnidipine 20 mg/die
Carvedilol 25 mg/die
Carvedilol 50 mg/die
Carvedilol 50 mg/die
Carvedilol 50 mg/die
Spironolactone 25 mg/die
Doxazosin 4 mg/die
Doxazosin 4 mg/die
Spironolactone 25 mg/die
Clonidine transdermal patch 5 mg
Spironolactone 25 mg/die
Spironolactone 25 mg/die
Clonidine transdermal patch 5 mg
Clonidine transdermal patch 5 mg
Clonidine transdermal patch 5 mg
RSD renal sympathetic denervation
Fig. 1 a Pre-procedural invasive blood pressure values; b preprocedural abdominal aortography showing a single, normal, left renal artery; c selective renal cannulation with the SymplicityTM
catheter tip during nerve ablation; d post-procedural selective angiography excluding vascular periprocedural complications
over the next 3 years was admitted several times for recurrence of chest pain caused by a hypertensive crisis in the absence of significant coronary stenosis. The patient underwent full diagnostic screening to exclude secondary causes of hypertension, that included: magnetic resonance (MR) angiography and abdominal ultrasonography (US), dosage of plasma and urinary electrolytes (Na, K) and plasma and urinary assay of aldosterone and plasma renin activity. After multidisciplinary evaluation he was scheduled for RSD.
Basal blood pressure at the beginning of the procedure (273/119 mmHg) required intravenous infusion of 10 mcg/ kg/min sodium nitroprusside to control blood pressure during the procedure (see Fig. 1a). Intravenous (i.v.) unfractionated heparin was given to maintain the activated clotting time (ACT)[250 s. Angiography of the abdominal aorta confirmed the presence of a single (left) kidney (Fig. 1b). After deep sedation and selective catheterization of the left renal artery with a 6F guiding catheter, a SymplicityTM catheter (Medtronic, Mountain View, CA, USA)
123
J Nephrol Fig. 2 Diagram showing the systolic and diastolic mean blood pressure trend at follow up
was advanced to reach the renal artery wall (Fig. 1c). Radiofrequency waves were administered in six different spots of the renal artery wall. The catheter-based RSD procedure aims to disrupt the afferent and efferent nerves passing through the adventitia of the renal arteries using radiofrequency energy, under fluoroscopic guidance, to achieve circumferential renal denervation. At the end of the procedure, left renal artery angiography showed structural integrity of the vessel wall (Fig. 1d) without evidence of blood flow impairment. Clinical in-office follow-up controls performed after the procedure showed a total lack of response during the first 3 months, but a clear anti-hypertensive effect was apparent at 24-h blood pressure monitoring performed at 6 months after the procedure, with a significant reduction in systolic and diastolic pressure compared to baseline (Fig. 2). At that time, the alpha-blocker therapy was stopped and the diuretic dose reduced from 250 mg of furosemide to 25 mg BID. At 9-month follow up, drug therapy was further reduced with a discontinuation of the calcium channel blockers and reduction of beta blockers, based on mean 24-h blood pressure (BP) values of 160 mmHg systolic BP and 80 mmHg diastolic BP (Table 1). Furthermore, the renal function, which represents a critical point for procedural safety evaluation, was unchanged over the entire follow-up (serum creatinine and eGFR at 9 months, respectively, 1.3 mg/dl and 67 ml/min/1.73 m2).
independent single center experiences [1–3]. Significant reductions by at least 20 mmHg in blood pressure have been reported with the Symplicity SRD system, and this achievement is consistent with a reduction of the clinical risk of major clinical events such as stroke and myocardial infarction [4]. The safety and efficacy of SRD in patients with a single kidney is, however, unknown. A first case recently reported, by Do¨rr et al. [5], showed the feasibility, but without data on long-term efficacy or renal function. The drop in blood pressure values reported at the 3-month follow-up, in our experience, sharply differs from that measured at the same follow-up time by Do¨rr et al. In this regard, the considerable high basal values in blood pressure, showed by our patient prior to the procedure, together with the severe resistance to anti-hypertensive medications, could be an adequate explanation for the delay in the blood pressure drop observed in our follow-up. Our report confirms the feasibility of RSD in this delicate context, without evident adverse effects and with a significant reduction of blood pressure after a latency period of 3–6 months after the procedure. Future reports and dedicated studies will help to better clarify the value of RSD in single-kidney patients.
Discussion
References
The feasibility, safety and efficacy of RSD have been demonstrated both in randomized control trials and
Conflict of interest The authors have no conflict of interest to report.
1. Investigators SH-2 (2010) Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity
123
J Nephrol HTN-2 Trial): a randomised controlled trial. Lancet 376:1903–1909 2. Symplicity HTN-1 Investigators (2011) Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension 57:911–917 3. Simonetti G, Spinelli A, Gandini R et al (2012) Endovascular radiofrequency renal denervation in treating refractory arterial hypertension: a preliminary experience. Radiol Med 117:426–444
123
4. Lloyd-Jones D, Adams RJ, Brown TM et al (2010) Heart disease and stroke statistics. 2010 Update: a report from the American Heart Association. Circulation 2010(121):e46–e215 5. Do¨rr O, Hamm C, Nef HM (2013) Single-side renal sympathetic denervation in a hypertensive patient with a single kidney. Am J Kidney Dis 61:1042–1043
CASE REPORT
Single-side renal sympathetic denervation to treat malignant refractory hypertension in a solitary kidney patient Flavio Ribichini • Angela Ferrara • Michele Pighi • Gabriele Pesarini • Alessia Gambaro • Enrico Valvo • Antonio Lupo • Corrado Vassanelli
Received: 19 August 2013 / Accepted: 22 November 2013 Ó Italian Society of Nephrology 2014
Abstract Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. Patients affected by renovascular or anatomical abnormalities have hitherto been systematically excluded from clinical trials with RSD because of concern about safety and the unknown efficacy of the procedure in this subgroup of patients. We describe the management of a case of RSD in a single-kidney patient with refractory hypertension; the patient had had a previous surgical right nephrectomy for renal cell carcinoma that subsequently required no other oncologic treatment. After multidisciplinary assessment, the patient underwent RSD. The procedure was performed through a 6F femoral access using the SymplicityTM RSD system (Medtronic, Mountain View, CA, USA). Radiofrequency was applied to the renal artery wall in 6 different points under general sedation with midazolam to control back pain caused by the procedure, that was performed without periprocedural complications. The patient was discharged 2 days later after a control of the vascular access site and routine biochemical examinations. The following 9-month follow up showed a significant reduction in blood pressure and stable renal function, without signs of renal damage. Our report confirms the feasibility of RSD in this delicate context, without evident negative effects on kidney function and with a significant reduction in blood pressure. Future studies are needed to fully clarify the value of RSD in single-kidney patients.
F. Ribichini (&) A. Ferrara M. Pighi G. Pesarini A. Gambaro E. Valvo A. Lupo C. Vassanelli Department of Medicine, University of Verona, Verona, Italy e-mail: [email protected]
Keywords Renal sympathetic denervation Refractory hypertension Solitary-kidney
Introduction Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. The safety and efficacy of this novel technique have been investigated in recent randomized controlled trials [1, 2], but patients affected by renovascular or anatomical abnormalities were systematically excluded from these clinical trials. In particular, patients having only one kidney due to congenital or post-surgical conditions have been banned from enrollment because of concern about safety and the unknown efficacy of the procedure in this subgroup of patients.
Case report A 56-year-old man with a single kidney was admitted to our Department for malignant arterial hypertension, refractory to medical therapy despite a full dose treatment with seven anti-hypertensive drugs (Table 1). The patient had undergone surgical right nephrectomy 15 years before, for renal cell carcinoma at the age of 40 years, that subsequently required no other oncologic treatment. He had also mild chronic renal failure (serum creatinine 1.5 mg/dl and estimated glomerular filtration rate (eGFR) 64 ml/min/1.73 m2) and several cardiovascular risk factors: diabetes mellitus, obesity, hypercholesterolemia and smoking. He developed arterial hypertension in 2008, and
123
J Nephrol Table 1 Changes in antihypertensive therapy after renal sympathetic denervation Pre-RSD
3 months Post-RSD
6 months Post-RSD
9 months POST-RSD
Furosemide 250 mg/die
Furosemide 250 mg/die
Furosemide 25 mg/die
Furosemide 25 mg/die
Telmisartan 120 mg/die
Telmisartan 120 mg/die
Telmisartan 120 mg/die
Telmisartan 120 mg/die
Barnidipine 20 mg/die
Barnidipine 20 mg/die
Barnidipine 20 mg/die
Carvedilol 25 mg/die
Carvedilol 50 mg/die
Carvedilol 50 mg/die
Carvedilol 50 mg/die
Spironolactone 25 mg/die
Doxazosin 4 mg/die
Doxazosin 4 mg/die
Spironolactone 25 mg/die
Clonidine transdermal patch 5 mg
Spironolactone 25 mg/die
Spironolactone 25 mg/die
Clonidine transdermal patch 5 mg
Clonidine transdermal patch 5 mg
Clonidine transdermal patch 5 mg
RSD renal sympathetic denervation
Fig. 1 a Pre-procedural invasive blood pressure values; b preprocedural abdominal aortography showing a single, normal, left renal artery; c selective renal cannulation with the SymplicityTM
catheter tip during nerve ablation; d post-procedural selective angiography excluding vascular periprocedural complications
over the next 3 years was admitted several times for recurrence of chest pain caused by a hypertensive crisis in the absence of significant coronary stenosis. The patient underwent full diagnostic screening to exclude secondary causes of hypertension, that included: magnetic resonance (MR) angiography and abdominal ultrasonography (US), dosage of plasma and urinary electrolytes (Na, K) and plasma and urinary assay of aldosterone and plasma renin activity. After multidisciplinary evaluation he was scheduled for RSD.
Basal blood pressure at the beginning of the procedure (273/119 mmHg) required intravenous infusion of 10 mcg/ kg/min sodium nitroprusside to control blood pressure during the procedure (see Fig. 1a). Intravenous (i.v.) unfractionated heparin was given to maintain the activated clotting time (ACT)[250 s. Angiography of the abdominal aorta confirmed the presence of a single (left) kidney (Fig. 1b). After deep sedation and selective catheterization of the left renal artery with a 6F guiding catheter, a SymplicityTM catheter (Medtronic, Mountain View, CA, USA)
123
J Nephrol Fig. 2 Diagram showing the systolic and diastolic mean blood pressure trend at follow up
was advanced to reach the renal artery wall (Fig. 1c). Radiofrequency waves were administered in six different spots of the renal artery wall. The catheter-based RSD procedure aims to disrupt the afferent and efferent nerves passing through the adventitia of the renal arteries using radiofrequency energy, under fluoroscopic guidance, to achieve circumferential renal denervation. At the end of the procedure, left renal artery angiography showed structural integrity of the vessel wall (Fig. 1d) without evidence of blood flow impairment. Clinical in-office follow-up controls performed after the procedure showed a total lack of response during the first 3 months, but a clear anti-hypertensive effect was apparent at 24-h blood pressure monitoring performed at 6 months after the procedure, with a significant reduction in systolic and diastolic pressure compared to baseline (Fig. 2). At that time, the alpha-blocker therapy was stopped and the diuretic dose reduced from 250 mg of furosemide to 25 mg BID. At 9-month follow up, drug therapy was further reduced with a discontinuation of the calcium channel blockers and reduction of beta blockers, based on mean 24-h blood pressure (BP) values of 160 mmHg systolic BP and 80 mmHg diastolic BP (Table 1). Furthermore, the renal function, which represents a critical point for procedural safety evaluation, was unchanged over the entire follow-up (serum creatinine and eGFR at 9 months, respectively, 1.3 mg/dl and 67 ml/min/1.73 m2).
independent single center experiences [1–3]. Significant reductions by at least 20 mmHg in blood pressure have been reported with the Symplicity SRD system, and this achievement is consistent with a reduction of the clinical risk of major clinical events such as stroke and myocardial infarction [4]. The safety and efficacy of SRD in patients with a single kidney is, however, unknown. A first case recently reported, by Do¨rr et al. [5], showed the feasibility, but without data on long-term efficacy or renal function. The drop in blood pressure values reported at the 3-month follow-up, in our experience, sharply differs from that measured at the same follow-up time by Do¨rr et al. In this regard, the considerable high basal values in blood pressure, showed by our patient prior to the procedure, together with the severe resistance to anti-hypertensive medications, could be an adequate explanation for the delay in the blood pressure drop observed in our follow-up. Our report confirms the feasibility of RSD in this delicate context, without evident adverse effects and with a significant reduction of blood pressure after a latency period of 3–6 months after the procedure. Future reports and dedicated studies will help to better clarify the value of RSD in single-kidney patients.
Discussion
References
The feasibility, safety and efficacy of RSD have been demonstrated both in randomized control trials and
Conflict of interest The authors have no conflict of interest to report.
1. Investigators SH-2 (2010) Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity
123
J Nephrol HTN-2 Trial): a randomised controlled trial. Lancet 376:1903–1909 2. Symplicity HTN-1 Investigators (2011) Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension 57:911–917 3. Simonetti G, Spinelli A, Gandini R et al (2012) Endovascular radiofrequency renal denervation in treating refractory arterial hypertension: a preliminary experience. Radiol Med 117:426–444
123
4. Lloyd-Jones D, Adams RJ, Brown TM et al (2010) Heart disease and stroke statistics. 2010 Update: a report from the American Heart Association. Circulation 2010(121):e46–e215 5. Do¨rr O, Hamm C, Nef HM (2013) Single-side renal sympathetic denervation in a hypertensive patient with a single kidney. Am J Kidney Dis 61:1042–1043
