Nephrol Dial Transplant (2002) 17: 1122–1125
Interesting Case
Percutaneous mechanical thrombectomy: a new approach in the treatment of acute renal-vein thrombosis Bernard G. Jaar1, Hyun S. Kim2, Milagros D. Samaniego1, Gunnar B. Lund2 and Mohamed G. Atta1 1
Department of Medicine, Division of Nephrology and 2Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Keywords: acute renal failure; Amplatz thrombectomy device; mechanical thrombectomy; membranous glomerulonephritis; nephrotic syndrome; renal-vein thrombosis
Introduction Renal-vein thrombosis (RVT), first described by Rayer in 1840 [1], is now a well-known complication of the nephrotic syndrome. It is most commonly associated with membranous glomerulonephritis, but it also occurs in other nephrotic states [2]. Anticoagulation is usually recommended as the first line of treatment, although recently there have been several reports of successful revascularization with thrombolytic therapy [3]. Recently, the Amplatz thrombectomy device (Microvena, White Bear Lake, MN, USA), a new recirculation device developed to mechanically macerate thrombus, has been used to treat deep venous thrombosis, massive pulmonary embolism, and acute occlusions of the femoral arteries [4–6]. In this report we describe the immediate and long-term outcome of a unique case of acute renal failure secondary to renal-vein thrombosis successfully treated with percutaneous mechanical thrombectomy using the Amplatz thrombectomy device (ATD).
Case A 58-year-old man was referred to the renal service for evaluation and treatment of acute renal failure with an admission serum creatinine of 3 mgudl. Previous medical history included nephrotic syndrome for the past 9 months with significant lower extremity oedema. Correspondence and offprint requests to: Bernard G. Jaar MD, Division of Nephrology, Johns Hopkins University School of Medicine, 1830 E. Monument Street, 4th floor, Baltimore, MD 21205, USA. Email:
[email protected] #
Two months prior to admission, serum creatinine was 1.3 mgudl and a 24-h urinary protein excretion documented 9.3 g of protein per 24 h. At that time the patient underwent a left kidney biopsy, revealing membranous glomerulonephritis. Renal ultrasound examination performed at the time of his kidney biopsy revealed a small right kidney of uncertain aetiology, which measured 8.3 cm in length, and a normal size left kidney measuring 11.3 cm in length. The patient had no history of hypertension or urinary-tract infection, and previous studies for renal-artery stenosis and urological anomaly were negative. Work-up for secondary causes of membranous glomerulonephritis was negative, including screening for malignancy. Treatment of his membranous glomerulonephritis had included steroids. On admission, the patient denied haematuria and flank pain. Physical examination revealed a welldeveloped white male. The blood pressure was 115u68 mmHg, heart rate was 66 beatsumin, respiration was 20 breathsumin, and temperature 36.48C. The oxygen saturation was 97% on room air. The lungs were clear to auscultation and cardiac examination revealed a normal S1, S2 with no S3, S4, murmur, or rub. The point of maximum impulse was not displaced. The abdomen was soft, not tender, there was no organomegaly, but ascites was present. There was no costovertebral angle tenderness, and no cyanosis or clubbing. The lower extremities revealed 4q pitting oedema to the thighs. Guaiac stool test was positive. The initial laboratory results demonstrated sodium 140 mEqul, potassium 4.5 mEqul, chloride 108 mEqul, bicarbonate 17 mEqul, glucose 146 mgudl, total cholesterol 382 mgudl, albumin 1.7 gudl, and total protein 4.2 gudl. The blood urea nitrogen was 98 mgudl and the serum creatinine was 3 mgudl from a baseline of 1.3 mgudl, measured 2 months earlier at the time of the patient’s kidney biopsy. A complete blood cell count revealed white blood cells 15 600umm3, haematocrit 28.0%, and platelets 372 000umm3. Urinalysis showed no casts, no crystals, but 3q proteinuria, 1–2 red blood cells, and 2–3 white blood cells per high-power field.
2002 European Renal Association–European Dialysis and Transplant Association
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Fig. 2. Follow-up magnetic resonance venography 10 weeks after mechanical thrombectomy showing persisting patency of the left renal vein.
Fig. 1. Angiogram showing partial resolution of the left renal vein thrombus with good forward flow from the left renal vein only 10 min after onset of percutaneous mechanical thrombectomy with the Amplatz device catheter.
The acute onset of renal failure in a patient with nephrotic syndrome secondary to membranous glomerulonephritis led to the suspicion of renal-vein thrombosis. A magnetic resonance venography (MRV) was performed and showed a hypo-intense signal consistent with thrombosis of the left renal vein (not shown). The right renal vein appeared patent. The patient was started and maintained on an infusion of heparin to keep activated partial thromboplastin time 1.5–2.0 times the control value. Seventy-two hours after admission, because of persistently elevated serum creatinine, he underwent a CO2 venogram that confirmed the presence of the left renal-vein thrombosis (Figure 1). Percutaneous mechanical thrombectomy of the left renal vein was performed, using the Amplatz thrombectomy device with significant resolution of the left renal vein thrombus (Figure 2). The patient tolerated the procedure very well without any complication.
digital subtraction angiography (DSA). Then an 8 Fr reinforced long vascular sheath (Arrow International) was introduced and placed in the left renal vein. An Amplatz thrombectomy device (Microvena) was introduced via the long vascular sheath and repeated passes through the renal vein thrombus were performed, monitored by DSA and fluoroscopy. After blood flow had been re-established, a 16 mm diameter 3 4 cm long angioplasty balloon (Boston Scientific Inc.) was inflated across the left renal vein, followed by more passes of the ATD. The procedure was terminated after the DSA demonstrated good forward flow from the left renal vein. Overall, 30 cc of gadolinium and 35 cc of Omnipaque 350 were used for the procedure.
Results Following the percutaneous mechanical left renal-vein thrombectomy, heparin infusion was continued for 6 days while anticoagulation was changed to warfarin. The patient serum creatinine progressively improved to 1.5 mgudl within 48 h following the percutaneous mechanical thrombectomy of the left renal vein. The patient was maintained on oral prednisone, and mycophenolate mofetil was added to his medical regimen on discharge. Two and a half months after the percutaneous mechanical thrombectomy, serum creatinine was stable at 1.5 mgudl, serum albumin had increased to 3.6 gudl, and urinary protein excretion had decreased to 2.7 gu24 h; follow-up MRV showed persisting patency of the left renal vein.
Technical aspect The right common femoral vein was punctured and a 7 Fr vascular sheath introduced. A 5 Fr angiographic catheter was placed in the left renal vein and renal-vein thrombosis was confirmed using gadolinium contrast
Discussion We report the first case of successful mechanical thrombectomy of RVT using the ATD catheter in a
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patient with membranous glomerulonephritis and ARF. Renal function improved within 48 h following the percutaneous mechanical thrombectomy, and follow-up MRV at two and a half months showed persisting patency of the left renal vein while the patient was maintained on warfarin. Renal-vein thrombosis is a well-known complication of the nephrotic syndrome. According to the reported series in the literature, the incidence of RVT in nephrotic syndrome varies from 5 to 62% [7]. Patients with nephrotic syndrome secondary to membranous glomerulonephritis have been reported to have the highest incidence of RVT. In a series reported by Llach et al. [8] of 151 patients with nephrotic syndrome, RVT was present in 33, and of these, 20 had membranous glomerulonephritis. The pathogenic mechanism by which the nephrotic syndrome leads to RVT is not well known. Nephrotic syndrome is characterized by a hypercoagulable state, and several haemostatic abnormalities have been described. Thrombocytosis has been reported by some authors [9] but not confirmed by others. However, platelet hyperaggregability has also been reported and found more consistently in the nephrotic syndrome [10]. Increased fibrinogen level represents the most constant plasma coagulation disorder in the nephrotic syndrome. Kanfer et al. [11] studied 45 nephrotic patients without renal failure; 35 had hyperfibrinogenaemia, with a mean plasma fibrinogen for the group of 630 mgudl. Furthermore, abnormal levels of natural inhibitors of coagulation have also been reported in a number of patients with nephrotic syndrome. Antithrombin III (AT III), an a2 globulin, is the main inhibitor of thrombin. An increased incidence of thromboembolic complications is usually observed when AT III concentrations are less than 75% of normal. Several authors have reported low levels of AT III in 40–60% of patients with nephrotic syndrome. Plasma AT III correlated positively with serum albumin level and negatively with proteinuria in these studies [12,13]. Furthermore, plasma levels of both protein C and protein S antigens were also elevated in nephrotic patients [14]. Several studies of fibrinolytic factors in nephrotic syndrome have generated conflicting results, preventing any clear conclusion [7]. Renal-vein thrombosis in nephrotic patients has been described more frequently in association with idiopathic membranous glomerulonephritis [15]. The long-term prognosis of the disease remains less clear. In 1983, Wagoner et al. [16] reported the outcome of 27 of 33 consecutive patients with nephrotic syndrome and documented idiopathic membranous glomerulonephritis. Of the 27 patients who underwent renal-vein angiography, 13 were found to have RVT. No patient received corticosteroids during the period of observation but patients with RVT were given warfarin for at least 1 year. After 2.5 years of follow-up, no thromboembolic events had occurred in the warfarin group and there was no significant difference in the rate of renal function deterioration or change in degree
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of proteinuria between patients with and without RVT. The rationale for the treatment of RVT is to preserve renal function and prevent thromboembolic complications. In addition to treating the underlying disease, the therapeutic management of most patients with acute RVT has traditionally involved anticoagulation, fibrinolytic treatment, and rarely surgical thrombectomy [17]. Systemic anticoagulation with intravenous heparin followed by treatment with oral vitamin K antagonists has been the standard treatment for acute RVT to prevent further propagation of the thrombus and thromboembolic complications. The optimal duration of warfarin therapy is unknown; however, as long as the nephrotic state persists, the patient with documented RVT or thromboembolic event is at high risk of a recurrence, potentially at the site of the initial thrombotic event. It seems reasonable to maintain anticoagulant therapy as long as the patient is nephrotic and has significant hypoalbuminaemia [17]. The successful use of thrombolytic agent in treating RVT began as early as 1969 [18]. To date, there are no published data on any large series of patients undergoing thrombolytic therapy for RVT. Moreover, the relative efficacy of heparin vs fibrinolytic agents in RVT remains undefined. In 1995, Markowitz et al. [3] reviewed the indication of thrombolytic therapy in renal-vein thrombosis. The authors analysed the outcome of 21 patients with renal thrombosis treated with thrombolytic therapy between 1968 and 1993. The patients’ ages ranged from 9 to 62 years, 67% were male, and 64% had biopsy-proven membranous glomerulonephritis, while 71% were known to be nephrotic and presented with flank pain. Thirtyeight per cent presented with acute renal failure while 24% had renal insufficiency. Overall, of the 21 patients treated with thrombolytic therapy, three (14%) died of bleeding complications. In 1988, Laville et al. [19] reviewed 27 cases of renal-vein thrombosis. Twentyfour patients presented with nephrotic syndrome and 15 had renal insufficiency. Renal biopsy performed in 20 patients revealed membranous glomerulonephritis in 70% of the cases. Renal-vein thrombosis was angiographically proven in all patients. Ten patients were treated by anticoagulation alone, nine by surgical thrombectomy, seven by thrombolysis, two did not receive any specific treatment, and one underwent successively thrombectomy and then thrombolysis. Eight of ten patients on anticoagulation lived beyond 2 months. In contrast, only four of seven patients treated with thrombolytic agents followed by anticoagulation lived beyond 2 months; the cause of death in the other three patients was haemorrhagic complications. Three of nine patients treated with surgical thrombectomy did not survive beyond 2 months. Surgical thrombectomy is rarely indicated and has been reserved usually for cases that prove refractory to medical therapy [19,20]. Thrombolytic therapy offers a more rapid and complete resolution than anticoagulation but at a much higher risk of haemorrhagic
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complications and even death [3,19]. In the case presented, thrombolytic therapy was avoided because of the increased risk of bleeding. Since the patient had persistent renal failure secondary to renal-vein thrombosis, more than 72 h after initiation of anticoagulation, percutaneous mechanical thrombectomy of the left renal vein using the ATD was recommended. The ATD is a percutaneous rotational catheter proven to homogenize thrombus [21]. Percutaneous mechanical thrombectomy with the ATD has proved effective in the treatment of acute occlusions of both the superficial and deep femoral arteries [6]. In another study, the ATD provided rapid debulking of thrombus in selected patients with massive pulmonary embolus and improved outcome of these cases [5]. Furthermore, the ATD was comparable to surgical thrombectomy in a randomized trial of occluded haemodialysis vascular access grafts. No statistically significant differences in primary or secondary patencies were seen [22]. The risk of thrombus reforming after thrombectomy is minimized with the concomitant use of heparin. Risk of thrombus from the ATD is also minimal since the Amplatz creates a vortex while pulverizing the embolus into fragments measuring 10–100 mm and has extremely low rates of embolism in in vitro studies [23]. Nazarian et al. [24] reported transient laboratory evidence of haemolysis in nine patients following mechanical thrombectomy using the ATD catheter. The level of haptoglobin decreased and the level of plasma-free haemoglobin increased in eight patients, with haemoglobinuria detected in one. In the case presented, no thromboembolic complication or haemolysis was observed; blood flow was restored rapidly in the left renal vein followed by a significant improvement in renal function. In conclusion, percutaneous mechanical thrombectomy using the Amplatz thrombectomy device catheter is technically feasible and safe. It provides an attractive and alternative option for the treatment of renal-vein thrombosis associated acute renal failure, particularly when anticoagulation or thrombolytic therapy has failed or is contraindicated. Additional experience is required to assess accurately the role of this form of treatment in patients with acute RVT. Furthermore, close follow-up of these patients is warranted, particularly if they have persistent nephroticrange proteinuria, because of the increased risk of recurrent thromboembolic events.
3. Markowitz GS, Brignol F, Burns E et al. Renal-vein thrombosis treated with thrombolytic therapy. Case report and brief review. Am J Kidney Dis 1995; 25: 801–806 4. Delomez M, Beregi JP, Willoteaux S et al. Mechanical thrombectomy in patients with deep venous thrombosis. Cardiovasc Intervent Radiol 2001; 24: 42–48 5. Uflacker R, Strange C, Vujic I. Massive pulmonary embolism. Preliminary results of treatment with the Amplatz thrombectomy device. J Vasc Intervent Radiol 1996; 7: 519–528 6. Gorich J, Rilinger N, Sokiranski R et al. Mechanical thrombolysis of acute occlusion of both the superficial and the deep femoral arteries using a thrombectomy device. AJR 1998; 170: 1177–1180 7. Llach F. Hypercoagulability, renal-vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 1985; 28: 429–439 8. Llach F, Koffler A, Finck E, Massry SG. On the incidence of renal-vein thrombosis in the nephrotic syndrome. Arch Intern Med 1977; 137: 33–36 9. Kanfer A. Coagulation factors in nephrotic syndrome. Am J Nephrol 1990; 10 [Suppl 1]: 63–68 10. Jackson CA, Greaves M, Patterson AD et al. Relationship between platelet aggregation, thromboxane synthesis and albumin concentration in nephrotic syndrome. Br J Haematol 1982; 52: 69–77 11. Kanfer A, Kleinknetch D, Broyer M, Josso F. Coagulation studies in 45 cases of nephrotic syndrome without uremia. Thromb Diathes Haemorrh 1970; 24: 562–571 12. Boneu B, Bouissou F, Abbal M et al. Comparison of progressive antithrombin activity and the concentration of three inhibitors in nephrotic syndrome. Thromb Haemost 1981; 46: 623–625 13. Kauffmann RH, Veltkamp JJ, Van Tilburg NH, Van Es LA. Acquired antithrombin III deficiency and thrombosis in the nephrotic syndrome. Am J Med 1978; 65: 607–613 14. Cosio FG, Harker C, Batard MA et al. Plasma concentrations of the natural anticoagulants protein C and protein S in patients with proteinuria. J Lab Clin Med 1985; 106: 218–222 15. Llach F, Papper S, Massry SG. The clinical spectrum of renal-vein thrombosis, acute and chronic. Am J Med 1980; 69: 819–827 16. Wagoner RD, Stanson AW, Holley KE, Winter CS. Renal-vein thrombosis in idiopathic membranous glomerulopathy and nephrotic syndrome. Incidence and significance. Kidney Int 1983; 23: 368–374 17. Llach F, Nikakhtar B. Renal thromboembolism, atheroembolism and renal vein thrombosis. In: Schrier RW, Gottschalk CW, eds. Diseases of the Kidney, 6th edn, Vol. II. Little, Brown and Co Inc., Boston, 1997; 1893–1918 18. Hamilton CR Jr, Keller JW, Johnson AD, Cader R. Renal vein thrombosis and pulmonary thromboembolism. Johns Hopkins Med J 1969; 124: 331–339 19. Laville M, Aguilera D, Maillet PJ et al. The prognosis of renal-vein thrombosis. A re-evaluation of 27 cases. Nephrol Dial Transplant 1988; 3: 247–256 20. Fein RL, Chait A, Leviton A. Renal vein thrombectomy for the treatment of renal vein thrombosis associated with the nephrotic syndrome. J Urol 1968; 99: 1–13 21. Muller-Hulsbeck S, Schwarzenberg H, Heller M. Guidewirecontrolled advancement of the Amplatz thrombectomy device. Cardiovasc Intervent Radiol 1998; 21: 84–87 22. Uflacker R, Rajagopalan PR, Vujic I, Stutley JE. Treatment of thrombosed dialysis access grafts. Randomized trial of surgical thrombectomy versus mechanical thrombectomy with the Amplatz device. J Vasc Intervent Radiol 1996; 7: 185–192 23. Muller-Hulsbeck S, Schwarzenberg H, Bangard C et al. Suction pump-supported aspiration thrombectomy: an in-vitro comparison fragmentation procedure. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1998; 168: 191–194 24. Nazarian GK, Qian Z, Coleman CC et al. Hemolytic effect of the Amplatz thrombectomy device. J Vasc Intervent Radiol 1994; 5: 155–160
Acknowledgement. Dr Jaar was supported by a grant of the National Institute of Health—National Institute of Digestive Diabetes and Kidney Diseases T32 DK07732.
References 1. Rayer P. Traite des maladies des reins et des alterations de la secretion urinaire. Paris, JB Baillere, 1840, Vol. 2, 590–599 2. Zucchelli P. Renal-vein thrombosis. Nephrol Dial Transplant 1992; 7 [Suppl 1]: S105–S108
Received for publication: 25.10.01 Accepted in revised form: 28.1.02
