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Bilateral nephrectomy for uncontrolled hypertension in hemodialysis patient: A forgotten option?
Ne´phrologie & The´rapeutique 10 (2014) 528–531
Available online at
ScienceDirect www.sciencedirect.com
Clinical case
Bilateral nephrectomy for uncontrolled hypertension in hemodialysis patient: A forgotten option? M. Knehtl a,*, S. Bevc a, R. Hojs a, G. Hlebicˇ b, R. Ekart c a
Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia Department of Urology, Clinic for Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia c Department of Dialysis, Clinic for Internal Medicine, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 April 2014 Accepted 8 July 2014
Resistant arterial hypertension in chronic hemodialysis patients is still a therapeutical challenge despite the development of modern antihypertensive drugs and dialysis procedures. Bilateral nephrectomy seems to be a forgotten option, although it has given good results. We present a case of a 39-year-old female chronic hemodialysis patient, in whom the problem of uncontrolled renal parenchymal hypertension remained despite multiple drug therapy and the ultrafiltration intensification. The problem was solved by bilateral nephrectomy. We discuss the role of bilateral nephrectomy for arterial hypertension control in chronic hemodialysis patients and the surgical and non-surgical options of nephrectomy. ß 2014 Association Socie´te´ de ne´phrologie. Publie´ par Elsevier Masson SAS. Tous droits re´serve´s.
Keywords: Hemodialysis Arterial hypertension Bilateral nephrectomy
1. Introduction Resistant arterial hypertension is still a challenge for clinicians [1]. Bilateral nephrectomy has been reported to be life-saving in the management of severe arterial hypertension, drug-resistant malignant arterial hypertension, renin-mediated arterial hypertension and in patients with end-stage renal disease before and on dialysis [2]. The new medical treatment of arterial hypertension has made the decision of bilateral nephrectomy complicated. The development of modern antihypertensive drugs, improvement of dialysis procedures, and renal sympathetic denervation has decreased the need for nephrectomy. Therefore, the surgical option in the treatment of malignant arterial hypertension seems to be forgotten [2]. 2. Case report In a 39-year-old woman, arterial hypertension had been present since the age of 9. She had vesico-ureteral reflux and repeated urinary tract infections since childhood. She was operated on twice, at the age of 9 and 10. At the age of 19, the patient was diagnosed with renal parenchymal hypertension as a consequence of chronic tubulointerstitial nephritis. Three years later, she was hospitalized because of severely elevated blood * Corresponding author. E-mail address: [email protected] (M. Knehtl).
pressure. At that time, second grade vesico-ureteral reflux was found on the left side and first grade on the right side. Ultrasound of the heart showed left ventricular hypertrophy with normal systolic function, a fundoscopy revealed no hypertensive changes. She was treated with a combination of nifedipin (2 20 mg/day), metoprolol (100 mg/day), furosemide (2 40 mg/day), doxazosin (2 8 mg/day) and clonidine (2 0.2 mg/day). Her systolic blood pressure was from 160 to 200 mm Hg and diastolic from 100 to 130 mm Hg. The serum creatinine level was 104 mmol/L and the chromium ethylenediamine tetra-acetic acid (CrEDTA) clearance was 68 ml/min/1.73m2. Two years later, the patient was admitted to the hospital again due to severely elevated blood pressure and a headache. She was taking the same antihypertensive drugs as two years before and additionally the combination of amiloride and hydrochlorothiazide. At that time glaucoma in both eyes was found. The serum creatinine concentration was 96 mmol/L. Her therapy had been modified to metoprolol (100 mg/day), amlodipine (10 mg/day), losartan (100 mg/day), doxazosin (2 4 mg/ day), clonidine (2 0.2 mg/day) and furosemide (40 mg/day). She was under nephrologic follow-up for another two years, when her creatinine was still normal, but her kidneys were already smaller (9 3.8 cm). She had no problems during her pregnancy and had a normal delivery a year later. Later she suffered for repeated urinary tract infections. At age 32, her serum creatinine concentration was still 102 mmol/L. The first hypertensive crisis occurred 6 years ago when she was admitted to the intensive care unit. On admission her blood pressure was 240/160 mm Hg, she reported a headache and vision
http://dx.doi.org/10.1016/j.nephro.2014.07.484 1769-7255/ß 2014 Association Socie´te´ de ne´phrologie. Publie´ par Elsevier Masson SAS. Tous droits re´serve´s.
M. Knehtl et al. / Ne´phrologie & The´rapeutique 10 (2014) 528–531
loss. The laboratory results showed normocytic anemia (60 g/L), serum creatinine concentration was 1040 mmol/L, and she had proteinuria of 3+ (dipstick). Her systolic blood pressure was from 160 to 200 mmHg, diastolic blood pressure from 100 to 120 mm Hg. She was temporarily treated by intravenous infusion of nitrate, combined with amlodipin, doxazosin, furosemid and bisoprolol. She became oliguric, we found end-stage renal disease and continuous venovenous hemodiafiltration (CVVHDF) was performed. Ultrasound showed small kidneys (right 8.5 cm 2.5 cm; left 9.4 2.8 cm) with hyperechogenic parenchyma. The computed tomography (CT) angiography of the renal arteries revealed no renal artery stenosis. Suprarenal pathology was excluded, serum catecholamine values were normal. The arteriovenous fistula was constructed and regular chronic hemodialysis treatment was initiated. The residual daily diuresis was from 200 to 800 mL. On discharge she was treated with a combination of minoxidil (2 10 mg), carvedilol (2 25 mg), perindopril (8 mg), nifedipin (40 mg) and high doses of furosemid (250 mg). Five months later the second hypertensive crisis occurred with a headache and visual deterioration. The patient had also lost her appetite and had been losing weight (she lost 17 kilos in 5 months). Because of ischemic optic neuropathy, which was not a part of the hypertensive crisis and was the cause of her bilateral blindness, she was treated with corticosteroids again. We performed a 48-hour ambulatory blood pressure measurement: her blood pressure during the day time was 143–221/89–140 mmHg (mean value 177/117) and 163–209/112–135 mmHg (mean value 185/123) during the night time with non-dipping pressure profile. A CT scan of brain was performed and it excluded intracranial bleeding or mass. The electrocardiogram showed left ventricular hypertrophy. On discharge she was taking minoxidil (2 10 mg/day), metroprolol (2 100 mg/day), furosemid (2 80 mg/day), amlodipin (10 mg/day), ramipril (10 mg/day) and doxazosin (8 mg/day). Six months later, she was admitted again because a third hypertensive crisis occurred. The blood pressure values during hemodialysis were 240/140 mmHg, she reported of a headache, fatigue and fainting episodes. The neurologic examination was normal. Her blood pressure during hospitalization was 150–160/ 100 mmHg, and her therapy was modified again. On discharge she was taking minoxidil (5 mg/day), metoprolol (2 200 mg/day), furosemid (2 80 mg/day), amlodipin (10 mg/day), ramipril (2 10 mg/day), valsartan (160 mg/day) and doxazosin (2 8 mg/day). Despite multiple antihypertensive medications and volume status control with achievement of optimal dry weight and good compliance of the patient, she remained hypertensive. Her chest x-ray showed a normal sized heart with no congestion and no effusions, the vena cava diameter was 1.4 cm (7 hours posthemodialysis measurement). The refractory arterial hypertension with life-threatening hypertensive crisis was the reason for a laparoscopic bilateral nephrectomy five months later. The antihypertensive medication was discontinued completely 2 months after the bilateral nephrectomy. The patient became asymptomatic and normo- to hypotensive with blood pressure 61–117/46– 75 mm Hg without antihypertensive medication during the follow-up period of 3 years. She is tolerating ultrafiltration well (2500–3000 mL in 4 hours). She is not interested in renal transplantation. 3. Discussion Nephrectomy as a treatment for arterial hypertension dates back to the 1930s and was a mainstay of treatment through the early 1960s. The use of nephrectomy declined subsequently, mainly due to the availability of newer drugs, including those that block the renin–angiotensin–aldosterone system [3]. According to the literature, bilateral nephrectomy is infrequently used as
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treatment for intractable arterial hypertension. The prevalence of bilateral nephrectomy varies between 0% and 7% in most countries [4]. Using various definitions of arterial hypertension, its prevalence in hemodialysis patients is up to 90% [5]. Arterial hypertension in hemodialysis patients is caused by sodium and water retention, activation of the renin–angiotensin–aldosterone system, and by increased activity of the sympathetic nervous system. In hemodialysis patients, blood pressure is usually plasma volumedependent [6]. Increased ultrafiltration rates on hemodialysis with resultant reduction of the plasma volume and body weight normalize elevated blood pressure in approximately 80% of hypertensive patients. In about 15% to 20%, however, arterial hypertension persists or even increases despite the reduction of plasma volume and therapy with multiple antihypertensive drugs [4,6]. In these few patients, bilateral nephrectomy is an option for treatment [4]. However, bilateral nephrectomy for the treatment of refractory arterial hypertension in chronic hemodialysis patients has been seldom carried out [6]. Patients whose blood pressure is not controlled by maintenance of dry weight have increased plasma renin activity and demonstrate a dramatic improvement in arterial hypertension control after interruption of the renin–angiotensin–aldosterone system by bilateral nephrectomy [5,7]. The bilateral nephrectomy not only reduces the levels of renin, aldosterone, and angiotensin II, causing a decrease of blood pressure, but also decreases sympathetic activity [6], which was found to be normal in hemodialysis patients with bilateral nephrectomy. This leads to the hypothesis that sympathetic over activity in uremia is caused by a neurogenic signal (carried by renal afferents) arising in the failing kidney [5,8]. Zazgornik et al. analyzed 10 hemodialysis patients with arterial hypertension and poor response to antihypertensive treatment (refractory arterial hypertension) [6]. The clinical state and quality of life improved in all patients in the study and antihypertensive treatment was no longer necessary [6]. We noticed the same in our patient. Biesenbach et al. in a retrospective study of 16 hemodialysis patients in whom bilateral nephrectomy was performed due to severe or malignant refractory arterial hypertension evaluated that the clinical condition and quality of life improved in all patients. In nine patients, antihypertensive treatment was no longer necessary, and five patients required continuation of only one antihypertensive agent [4]. Controversy exists about the time course of blood pressure normalization in hypertensive patients after bilateral nephrectomy. Schwarz et al. retrospectively analyzed the course of blood pressure in 14 hypertensive patients and found that it did not normalize immediately following bilateral nephrectomy [9]. Six months after bilateral nephrectomy, blood pressure was significantly reduced compared to preoperative values, but antihypertensive medication had to be continued in the majority of patients (71%). It remains unclear, why anephric patients demonstrate this course of blood pressure reduction. Some patients had episodes of hypotension, while others still needed combined antihypertensive therapy. No difference between the patients was found regarding the duration of arterial hypertension or the primary cause of renal failure [9]. Bilateral nephrectomy can be done using various approaches, e.g. open transperitoneal (subcostal, flank, midline incisions) [10–12], bilateral dorsal lumbotomy [12–14] or by transperitoneal laparoscopy [12]. Open bilateral pretransplant nephrectomy was associated with high morbidity and mortality, as reported in some of the earlier series with values of 3.6–4% and 18–40%, respectively, in 1970 [10–12]. These patients had nephrectomy by an open transperitoneal approach. Bilateral posterior lumbotomy has been described for removing small kidneys to reduce morbidity of the open procedure [12].
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Krol et al. analyzed retrospectively the complications associated with simultaneous transabdominal bilateral nephrectomy in 20 hemodialysis patients (18 patients had autosomaldominant polycystic kidney disease, two patients had vesicoureteral reflux with chronic pyelonephritis) who were potential kidney graft recipients. In all cases the kidneys were removed transperitoneally via a transverse or midline incision. No fatal outcome was recorded. The only intraoperative complication was spleen injury in five patients. Surgical postoperative complications developed in nine patients (45%) including: extended drainage and delayed wound healing, postoperative hernia, prolonged abdominal pain, perihepatic hematoma, stress duodenal ulceration, and subileus. However, the authors concluded that the beneficial consequences of bilateral nephrectomy exceeded the surgical complications and were also related to the blood pressure decline after the operation [15]. The risks of open nephrectomy are well recognized, and laparoscopic nephrectomy may provide a favorable alternative [16]. Fornara et al., in a retrospective study, reported the outcomes of laparoscopic bilateral nephrectomy for treating hypertension in 11 renal transplant patients who were compared to ten who had open bilateral nephrectomy. In the laparoscopy group the mean operative time was longer, blood loss was higher and one patient required conversion to open surgery. Compared with the laparoscopy group, the interval to resumption of oral intake, duration of hospital stay and return to normal activities were longer in the open surgery group. In that study all patients in the open nephrectomy group had open transperitoneal nephrectomy [12,17]. Compared to open nephrectomy, laparoscopic nephrectomy offers shorter hospital stay and convalescence time, minimal loss of productivity, better cost-effectiveness, reduction in analgesic requirements, and better cosmetic results [18–23]. However, many conditions concerning mainly the anesthesia procedures do affect the laparoscopic success of uremic patients [24]. Chronic kidney disease is associated with metabolic acidosis that can be aggravated with carbon dioxide (CO2) insufflation during laparoscopic surgery. Briefly, insufflation with CO2 may affect respiratory capacity, especially when an underlying predisposing condition exists. Furthermore, pneumoperitoneum reduces lung capacity and pulmonary compliance [24,25]. Hypercapnia consequently may deteriorate the underlying chronic metabolic acidosis of the uremic patients leading to cardiovascular collapse and fatal arrhythmias [24,26]. Despite these increased risks of anesthesia Sanli et al. revealed that laparoscopic nephrectomy in hemodialysis patients might be performed safely under the expertise of an experienced laparoscopy team, considering perioperative outcomes comparable to those obtained in patients without renal failure [24]. Accordingly, laparoscopic nephrectomy should be considered as the procedure of choice for hemodialysis patients with the benefit of low morbidity [24]. In the study with a similar methodology, Fornara et al. compared 19 hemodialysis patients with 20 consecutive patients with normal renal function [27]. The authors noted four (21%) minor complications, such as fever and thrombotic occlusion of arteriovenous fistula in the dialysis group, and two complications (one pulmonary infection and one urinary tract infection) in the non-dialysis group [27]. In the largest study, performed by Shoma et al. in patients with chronic kidney disease, the conversion rate to open surgery was reported in 6% (4/64), whereas major and minor complication rates were detected in 6% and 9.2%, respectively [28]. However, Srivastava et al. concluded that bilateral dorsal lumbotomy appears to be better than transperitoneal laparoscopy
in small kidneys because the surgery is quicker, and there is earlier bowel recovery and lower costs. Fifty-eight patients in that study with end-stage renal disease and small kidneys underwent pretransplant bilateral nephrectomy for various indications, most commonly uncontrolled hypertension [12]. There are also two other non-surgical options of nephrectomy for refractory hypertension, which are renal artery embolization and catheter-based renal nerve ablation [29,30]. Bilateral renal embolization was introduced in refractory hypertension control in end-stage renal disease patients to reduce surgical traumatic injury and related complications, and it gained wide clinical application for minimal invasion, solid efficacy and relatively lower technique requirements compared with open or laparoscopic nephrectomy [29,31–34]. The study of Mao et al. showed that unilateral renal embolization is as effective as bilateral renal embolization in treating severe refractory hypertension in hemodialysis patients, with advantages over bilateral renal embolization in residual renal function preservation and milder post-infarction syndrome [29]. An interesting finding in this study was that renal embolization could decrease the plasma endothelin-1 concentration, which might contribute, at least partly, to the reductive effect on blood pressure [29,35]. Efferent sympathetic outflow and afferent neural signaling from the failing native kidneys are key mediators and can be targeted by renal denervation. Renal sensory afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control such as the heart and peripheral blood vessels, mainly by modulating posterior hypothalamic activity [30,31]. The recent introduction of a catheter-based radio frequency ablation approach to directly target both efferent and afferent renal nerves appears to be a useful therapeutic approach. Indeed, recent clinical trials in patients with resistant hypertension and normal renal function demonstrated the safety and efficacy of renal sympathetic denervation [30,36–38]. Furthermore, there is accumulating evidence of additional beneficial effects of renal denervation on central sympathetic nerve activity and insulin sensitivity [30,39–41], both of which are of particular relevance in patients with end-stage renal disease [30]. Schlaich et al. in his study concluded that renal denervation is feasible in patients with end-stage renal disease and is associated with a sustained reduction in systolic office blood pressure. However, atrophic renal arteries may pose a problem for application of this technology in some patients with end-stage renal disease [30]. 4. Conclusions In our patient with end-stage renal disease due to chronic tubulointerstitial nephritis the laparoscopic bilateral nephrectomy was a possible option and a definite complete solution for uncontrolled renal parenchymal hypertension, which could not be managed by multiple antihypertensive agents and dry weight optimization during hemodialysis. The future will show if the forgotten bilateral nephrectomy will become an option again. The non-surgical options of nephrectomy for refractory hypertension are still reserved in certain centers and need to be fully evaluated. Currently bilateral nephrectomy still represents a definite option for arterial hypertension control in patients with end-stage renal disease. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
M. Knehtl et al. / Ne´phrologie & The´rapeutique 10 (2014) 528–531
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[22] Sosa RE, Seiba M, Shichman S. Hand-assisted laparoscopic surgery. Semin Laparosc Surg 2000;7:185–94. [23] Traxer O, Pearle MS. Laparoscopic nephrectomy for benign diseases. Semin Laparosc Surg 2000;7:176–84. [24] Sanli O, Tefik T, Ortac M, Karadeniz M, Oktar T, Nane I, et al. Laparoscopic nephrectomy in patients undergoing hemodialysis treatment. JSLS 2010; 14(4):534–40. [25] Ekman LG, Abrahamsson J, Biber B, Forssman L, Milsom I, Sjo¨qvist BA. Hemodynamic changes during laparoscopy with positive end-expiratory pressure ventilation. Acta Anaesthesiol Scand 1988;32:447–53. [26] Wolf Jr JS. The physiology of laparoscopic genitourinary surgery. In: Moore RG, Bishoff JT, Loening S, Docimo SG, editors. Minimal invasive urologic surgery. Abingdon: Taylor & Francis; 2005. p. 115–29. [27] Fornara P, Doehn C, Miglietti G, Fricke L, Steinhoff J, Sack K, et al. Laparoscopic nephrectomy: comparison of dialysis and non-dialysis patients. Nephrol Dial Transplant 1998;13(5):1221–5. [28] Shoma AM, Eraky I, El-Kappany HA. Pretransplant native nephrectomy in patients with end-stage renal failure: assessment of the role of laparoscopy. Urology 2003;61:915–20. [29] Mao Z, Ye C, Zhao X, et al. Comparison of unilateral renal artery embolization versus bilateral for treatment of severe refractory hypertension in hemodialysis patients. World J Urol 2009;27(5):679–85. [30] Schlaich MP, Bart B, Hering D, et al. Feasibility of catheter-based renal nerve ablation and effects on sympathetic nerve activity and blood pressure in patients with end-stage renal disease. Int J Cardiol 2013;168(3):2214–20. [31] Hom D, Eiley D, Lumerman JH, Siegel DN, Goldfischer ER, Smith AD. Complete renal embolization as an alternative to nephrectomy. J Urol 1999;161:24–7. [32] De Baere T, Lagrange C, Kuoch V, Morice P, Court B, Roche A. Transcatheter ethanol renal ablation in 20 patients with persistent urine leaks: an alternative to surgical nephrectomy. J Urol 2000;164:1148–52. [33] Golwyn Jr DH, Routh WD, Chen MY, Lorentz WB, Dyer RB. Percutaneous transcatheter renal ablation with absolute ethanol for uncontrolled hypertension or nephrotic syndrome: results in 11 patients with end-stage renal disease. J Vasc Interv Radiol 1997;8:527–33. [34] Basile A, Boullosa-Seoane E, Dominiguez-Viguera L, Certo A, Casal-Rivas M. Bilateral renal embolization in the treatment of patients with renal insufficiency and arterial hypertension: report of a case of polycystic kidneys. Radiol Med (Torino) 2002;103:555–7. [35] Tostes RC, Fortes ZB, Callera GE, Montezano AC, Touyz RM, Webb RC, et al. Endothelin, sex and hypertension. Clin Sci (Lond) 2008;114:85–97. [36] Campese VM, Kogosov E. Renal afferent denervation prevents hypertension in rats with chronic renal failure. Hypertension 1995;25:878–82. [37] Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 2009;373: 1275–81. [38] Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 2010;376: 1903–9. [39] Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD. Renal sympatheticnerve ablation for uncontrolled hypertension. N Engl J Med 2009;361:932–4. [40] Schlaich MP, Straznicky N, Grima M, Ika-Sari C, Dawood T, Mahfoud F, et al. Renal denervation: a potential new treatment modality for polycystic ovary syndrome? J Hypertens 2011;29:991–6. [41] Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation 2011;123:1940–6.
Available online at
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Clinical case
Bilateral nephrectomy for uncontrolled hypertension in hemodialysis patient: A forgotten option? M. Knehtl a,*, S. Bevc a, R. Hojs a, G. Hlebicˇ b, R. Ekart c a
Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia Department of Urology, Clinic for Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia c Department of Dialysis, Clinic for Internal Medicine, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 April 2014 Accepted 8 July 2014
Resistant arterial hypertension in chronic hemodialysis patients is still a therapeutical challenge despite the development of modern antihypertensive drugs and dialysis procedures. Bilateral nephrectomy seems to be a forgotten option, although it has given good results. We present a case of a 39-year-old female chronic hemodialysis patient, in whom the problem of uncontrolled renal parenchymal hypertension remained despite multiple drug therapy and the ultrafiltration intensification. The problem was solved by bilateral nephrectomy. We discuss the role of bilateral nephrectomy for arterial hypertension control in chronic hemodialysis patients and the surgical and non-surgical options of nephrectomy. ß 2014 Association Socie´te´ de ne´phrologie. Publie´ par Elsevier Masson SAS. Tous droits re´serve´s.
Keywords: Hemodialysis Arterial hypertension Bilateral nephrectomy
1. Introduction Resistant arterial hypertension is still a challenge for clinicians [1]. Bilateral nephrectomy has been reported to be life-saving in the management of severe arterial hypertension, drug-resistant malignant arterial hypertension, renin-mediated arterial hypertension and in patients with end-stage renal disease before and on dialysis [2]. The new medical treatment of arterial hypertension has made the decision of bilateral nephrectomy complicated. The development of modern antihypertensive drugs, improvement of dialysis procedures, and renal sympathetic denervation has decreased the need for nephrectomy. Therefore, the surgical option in the treatment of malignant arterial hypertension seems to be forgotten [2]. 2. Case report In a 39-year-old woman, arterial hypertension had been present since the age of 9. She had vesico-ureteral reflux and repeated urinary tract infections since childhood. She was operated on twice, at the age of 9 and 10. At the age of 19, the patient was diagnosed with renal parenchymal hypertension as a consequence of chronic tubulointerstitial nephritis. Three years later, she was hospitalized because of severely elevated blood * Corresponding author. E-mail address: [email protected] (M. Knehtl).
pressure. At that time, second grade vesico-ureteral reflux was found on the left side and first grade on the right side. Ultrasound of the heart showed left ventricular hypertrophy with normal systolic function, a fundoscopy revealed no hypertensive changes. She was treated with a combination of nifedipin (2 20 mg/day), metoprolol (100 mg/day), furosemide (2 40 mg/day), doxazosin (2 8 mg/day) and clonidine (2 0.2 mg/day). Her systolic blood pressure was from 160 to 200 mm Hg and diastolic from 100 to 130 mm Hg. The serum creatinine level was 104 mmol/L and the chromium ethylenediamine tetra-acetic acid (CrEDTA) clearance was 68 ml/min/1.73m2. Two years later, the patient was admitted to the hospital again due to severely elevated blood pressure and a headache. She was taking the same antihypertensive drugs as two years before and additionally the combination of amiloride and hydrochlorothiazide. At that time glaucoma in both eyes was found. The serum creatinine concentration was 96 mmol/L. Her therapy had been modified to metoprolol (100 mg/day), amlodipine (10 mg/day), losartan (100 mg/day), doxazosin (2 4 mg/ day), clonidine (2 0.2 mg/day) and furosemide (40 mg/day). She was under nephrologic follow-up for another two years, when her creatinine was still normal, but her kidneys were already smaller (9 3.8 cm). She had no problems during her pregnancy and had a normal delivery a year later. Later she suffered for repeated urinary tract infections. At age 32, her serum creatinine concentration was still 102 mmol/L. The first hypertensive crisis occurred 6 years ago when she was admitted to the intensive care unit. On admission her blood pressure was 240/160 mm Hg, she reported a headache and vision
http://dx.doi.org/10.1016/j.nephro.2014.07.484 1769-7255/ß 2014 Association Socie´te´ de ne´phrologie. Publie´ par Elsevier Masson SAS. Tous droits re´serve´s.
M. Knehtl et al. / Ne´phrologie & The´rapeutique 10 (2014) 528–531
loss. The laboratory results showed normocytic anemia (60 g/L), serum creatinine concentration was 1040 mmol/L, and she had proteinuria of 3+ (dipstick). Her systolic blood pressure was from 160 to 200 mmHg, diastolic blood pressure from 100 to 120 mm Hg. She was temporarily treated by intravenous infusion of nitrate, combined with amlodipin, doxazosin, furosemid and bisoprolol. She became oliguric, we found end-stage renal disease and continuous venovenous hemodiafiltration (CVVHDF) was performed. Ultrasound showed small kidneys (right 8.5 cm 2.5 cm; left 9.4 2.8 cm) with hyperechogenic parenchyma. The computed tomography (CT) angiography of the renal arteries revealed no renal artery stenosis. Suprarenal pathology was excluded, serum catecholamine values were normal. The arteriovenous fistula was constructed and regular chronic hemodialysis treatment was initiated. The residual daily diuresis was from 200 to 800 mL. On discharge she was treated with a combination of minoxidil (2 10 mg), carvedilol (2 25 mg), perindopril (8 mg), nifedipin (40 mg) and high doses of furosemid (250 mg). Five months later the second hypertensive crisis occurred with a headache and visual deterioration. The patient had also lost her appetite and had been losing weight (she lost 17 kilos in 5 months). Because of ischemic optic neuropathy, which was not a part of the hypertensive crisis and was the cause of her bilateral blindness, she was treated with corticosteroids again. We performed a 48-hour ambulatory blood pressure measurement: her blood pressure during the day time was 143–221/89–140 mmHg (mean value 177/117) and 163–209/112–135 mmHg (mean value 185/123) during the night time with non-dipping pressure profile. A CT scan of brain was performed and it excluded intracranial bleeding or mass. The electrocardiogram showed left ventricular hypertrophy. On discharge she was taking minoxidil (2 10 mg/day), metroprolol (2 100 mg/day), furosemid (2 80 mg/day), amlodipin (10 mg/day), ramipril (10 mg/day) and doxazosin (8 mg/day). Six months later, she was admitted again because a third hypertensive crisis occurred. The blood pressure values during hemodialysis were 240/140 mmHg, she reported of a headache, fatigue and fainting episodes. The neurologic examination was normal. Her blood pressure during hospitalization was 150–160/ 100 mmHg, and her therapy was modified again. On discharge she was taking minoxidil (5 mg/day), metoprolol (2 200 mg/day), furosemid (2 80 mg/day), amlodipin (10 mg/day), ramipril (2 10 mg/day), valsartan (160 mg/day) and doxazosin (2 8 mg/day). Despite multiple antihypertensive medications and volume status control with achievement of optimal dry weight and good compliance of the patient, she remained hypertensive. Her chest x-ray showed a normal sized heart with no congestion and no effusions, the vena cava diameter was 1.4 cm (7 hours posthemodialysis measurement). The refractory arterial hypertension with life-threatening hypertensive crisis was the reason for a laparoscopic bilateral nephrectomy five months later. The antihypertensive medication was discontinued completely 2 months after the bilateral nephrectomy. The patient became asymptomatic and normo- to hypotensive with blood pressure 61–117/46– 75 mm Hg without antihypertensive medication during the follow-up period of 3 years. She is tolerating ultrafiltration well (2500–3000 mL in 4 hours). She is not interested in renal transplantation. 3. Discussion Nephrectomy as a treatment for arterial hypertension dates back to the 1930s and was a mainstay of treatment through the early 1960s. The use of nephrectomy declined subsequently, mainly due to the availability of newer drugs, including those that block the renin–angiotensin–aldosterone system [3]. According to the literature, bilateral nephrectomy is infrequently used as
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treatment for intractable arterial hypertension. The prevalence of bilateral nephrectomy varies between 0% and 7% in most countries [4]. Using various definitions of arterial hypertension, its prevalence in hemodialysis patients is up to 90% [5]. Arterial hypertension in hemodialysis patients is caused by sodium and water retention, activation of the renin–angiotensin–aldosterone system, and by increased activity of the sympathetic nervous system. In hemodialysis patients, blood pressure is usually plasma volumedependent [6]. Increased ultrafiltration rates on hemodialysis with resultant reduction of the plasma volume and body weight normalize elevated blood pressure in approximately 80% of hypertensive patients. In about 15% to 20%, however, arterial hypertension persists or even increases despite the reduction of plasma volume and therapy with multiple antihypertensive drugs [4,6]. In these few patients, bilateral nephrectomy is an option for treatment [4]. However, bilateral nephrectomy for the treatment of refractory arterial hypertension in chronic hemodialysis patients has been seldom carried out [6]. Patients whose blood pressure is not controlled by maintenance of dry weight have increased plasma renin activity and demonstrate a dramatic improvement in arterial hypertension control after interruption of the renin–angiotensin–aldosterone system by bilateral nephrectomy [5,7]. The bilateral nephrectomy not only reduces the levels of renin, aldosterone, and angiotensin II, causing a decrease of blood pressure, but also decreases sympathetic activity [6], which was found to be normal in hemodialysis patients with bilateral nephrectomy. This leads to the hypothesis that sympathetic over activity in uremia is caused by a neurogenic signal (carried by renal afferents) arising in the failing kidney [5,8]. Zazgornik et al. analyzed 10 hemodialysis patients with arterial hypertension and poor response to antihypertensive treatment (refractory arterial hypertension) [6]. The clinical state and quality of life improved in all patients in the study and antihypertensive treatment was no longer necessary [6]. We noticed the same in our patient. Biesenbach et al. in a retrospective study of 16 hemodialysis patients in whom bilateral nephrectomy was performed due to severe or malignant refractory arterial hypertension evaluated that the clinical condition and quality of life improved in all patients. In nine patients, antihypertensive treatment was no longer necessary, and five patients required continuation of only one antihypertensive agent [4]. Controversy exists about the time course of blood pressure normalization in hypertensive patients after bilateral nephrectomy. Schwarz et al. retrospectively analyzed the course of blood pressure in 14 hypertensive patients and found that it did not normalize immediately following bilateral nephrectomy [9]. Six months after bilateral nephrectomy, blood pressure was significantly reduced compared to preoperative values, but antihypertensive medication had to be continued in the majority of patients (71%). It remains unclear, why anephric patients demonstrate this course of blood pressure reduction. Some patients had episodes of hypotension, while others still needed combined antihypertensive therapy. No difference between the patients was found regarding the duration of arterial hypertension or the primary cause of renal failure [9]. Bilateral nephrectomy can be done using various approaches, e.g. open transperitoneal (subcostal, flank, midline incisions) [10–12], bilateral dorsal lumbotomy [12–14] or by transperitoneal laparoscopy [12]. Open bilateral pretransplant nephrectomy was associated with high morbidity and mortality, as reported in some of the earlier series with values of 3.6–4% and 18–40%, respectively, in 1970 [10–12]. These patients had nephrectomy by an open transperitoneal approach. Bilateral posterior lumbotomy has been described for removing small kidneys to reduce morbidity of the open procedure [12].
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Krol et al. analyzed retrospectively the complications associated with simultaneous transabdominal bilateral nephrectomy in 20 hemodialysis patients (18 patients had autosomaldominant polycystic kidney disease, two patients had vesicoureteral reflux with chronic pyelonephritis) who were potential kidney graft recipients. In all cases the kidneys were removed transperitoneally via a transverse or midline incision. No fatal outcome was recorded. The only intraoperative complication was spleen injury in five patients. Surgical postoperative complications developed in nine patients (45%) including: extended drainage and delayed wound healing, postoperative hernia, prolonged abdominal pain, perihepatic hematoma, stress duodenal ulceration, and subileus. However, the authors concluded that the beneficial consequences of bilateral nephrectomy exceeded the surgical complications and were also related to the blood pressure decline after the operation [15]. The risks of open nephrectomy are well recognized, and laparoscopic nephrectomy may provide a favorable alternative [16]. Fornara et al., in a retrospective study, reported the outcomes of laparoscopic bilateral nephrectomy for treating hypertension in 11 renal transplant patients who were compared to ten who had open bilateral nephrectomy. In the laparoscopy group the mean operative time was longer, blood loss was higher and one patient required conversion to open surgery. Compared with the laparoscopy group, the interval to resumption of oral intake, duration of hospital stay and return to normal activities were longer in the open surgery group. In that study all patients in the open nephrectomy group had open transperitoneal nephrectomy [12,17]. Compared to open nephrectomy, laparoscopic nephrectomy offers shorter hospital stay and convalescence time, minimal loss of productivity, better cost-effectiveness, reduction in analgesic requirements, and better cosmetic results [18–23]. However, many conditions concerning mainly the anesthesia procedures do affect the laparoscopic success of uremic patients [24]. Chronic kidney disease is associated with metabolic acidosis that can be aggravated with carbon dioxide (CO2) insufflation during laparoscopic surgery. Briefly, insufflation with CO2 may affect respiratory capacity, especially when an underlying predisposing condition exists. Furthermore, pneumoperitoneum reduces lung capacity and pulmonary compliance [24,25]. Hypercapnia consequently may deteriorate the underlying chronic metabolic acidosis of the uremic patients leading to cardiovascular collapse and fatal arrhythmias [24,26]. Despite these increased risks of anesthesia Sanli et al. revealed that laparoscopic nephrectomy in hemodialysis patients might be performed safely under the expertise of an experienced laparoscopy team, considering perioperative outcomes comparable to those obtained in patients without renal failure [24]. Accordingly, laparoscopic nephrectomy should be considered as the procedure of choice for hemodialysis patients with the benefit of low morbidity [24]. In the study with a similar methodology, Fornara et al. compared 19 hemodialysis patients with 20 consecutive patients with normal renal function [27]. The authors noted four (21%) minor complications, such as fever and thrombotic occlusion of arteriovenous fistula in the dialysis group, and two complications (one pulmonary infection and one urinary tract infection) in the non-dialysis group [27]. In the largest study, performed by Shoma et al. in patients with chronic kidney disease, the conversion rate to open surgery was reported in 6% (4/64), whereas major and minor complication rates were detected in 6% and 9.2%, respectively [28]. However, Srivastava et al. concluded that bilateral dorsal lumbotomy appears to be better than transperitoneal laparoscopy
in small kidneys because the surgery is quicker, and there is earlier bowel recovery and lower costs. Fifty-eight patients in that study with end-stage renal disease and small kidneys underwent pretransplant bilateral nephrectomy for various indications, most commonly uncontrolled hypertension [12]. There are also two other non-surgical options of nephrectomy for refractory hypertension, which are renal artery embolization and catheter-based renal nerve ablation [29,30]. Bilateral renal embolization was introduced in refractory hypertension control in end-stage renal disease patients to reduce surgical traumatic injury and related complications, and it gained wide clinical application for minimal invasion, solid efficacy and relatively lower technique requirements compared with open or laparoscopic nephrectomy [29,31–34]. The study of Mao et al. showed that unilateral renal embolization is as effective as bilateral renal embolization in treating severe refractory hypertension in hemodialysis patients, with advantages over bilateral renal embolization in residual renal function preservation and milder post-infarction syndrome [29]. An interesting finding in this study was that renal embolization could decrease the plasma endothelin-1 concentration, which might contribute, at least partly, to the reductive effect on blood pressure [29,35]. Efferent sympathetic outflow and afferent neural signaling from the failing native kidneys are key mediators and can be targeted by renal denervation. Renal sensory afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control such as the heart and peripheral blood vessels, mainly by modulating posterior hypothalamic activity [30,31]. The recent introduction of a catheter-based radio frequency ablation approach to directly target both efferent and afferent renal nerves appears to be a useful therapeutic approach. Indeed, recent clinical trials in patients with resistant hypertension and normal renal function demonstrated the safety and efficacy of renal sympathetic denervation [30,36–38]. Furthermore, there is accumulating evidence of additional beneficial effects of renal denervation on central sympathetic nerve activity and insulin sensitivity [30,39–41], both of which are of particular relevance in patients with end-stage renal disease [30]. Schlaich et al. in his study concluded that renal denervation is feasible in patients with end-stage renal disease and is associated with a sustained reduction in systolic office blood pressure. However, atrophic renal arteries may pose a problem for application of this technology in some patients with end-stage renal disease [30]. 4. Conclusions In our patient with end-stage renal disease due to chronic tubulointerstitial nephritis the laparoscopic bilateral nephrectomy was a possible option and a definite complete solution for uncontrolled renal parenchymal hypertension, which could not be managed by multiple antihypertensive agents and dry weight optimization during hemodialysis. The future will show if the forgotten bilateral nephrectomy will become an option again. The non-surgical options of nephrectomy for refractory hypertension are still reserved in certain centers and need to be fully evaluated. Currently bilateral nephrectomy still represents a definite option for arterial hypertension control in patients with end-stage renal disease. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
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