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Renal contraction therapy for enlarged polycystic kidneys by transcatheter arterial embolization in hemodialysis patients
Renal Contraction Therapy for Enlarged Polycystic Kidneys by Transcatheter Arterial Embolization in Hemodialysis Patients Yoshifumi Ubara, MD, Tetsuo Tagami, MD, Naoki Sawa, MD, Hideyuki Katori, MD, Masafumi Yokota, MD, Fumi Takemoto, MD, Sumio Inoue, MD, Keihachirou Kuzuhara, MD, Shigeko Hara, MD, and Akira Yamada, MD ● Kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) usually continue to increase in size, even after patients begin dialysis therapy, and the mass effects may lead to severe complications. Such external conventional therapies as surgical and laparoscopic procedures have not yielded satisfactory results. Because kidneys in patients with ADPKD usually are supplied by well-developed arteries, we attempted renal contraction therapy in patients with ADPKD by renal transcatheter arterial embolization (TAE) using intravascular coils. After obtaining informed consent, we selected anuric patients on dialysis therapy with markedly distended abdomens or macroscopic hematuria. Between October 1996 and December 2000, a total of 64 patients were treated. Renal size, abdominal circumference, dry weight, hematocrit, and insulin-like growth factor-I were measured before TAE and 3, 6, and 12 months after TAE. Renal sizes decreased to 73.8% ⴞ 12.0%, 61.7% ⴞ 14.7%, and 53.4% ⴞ 11.6% of preinterventional values at 3, 6, and 12 months after therapy, respectively (P < 0.0001). Abdominal circumference and dry weight were significantly decreased at 3, 6, and 12 months (P < 0.0001) compared with baseline values before therapy. Hematocrits increased sequentially after 3, 6, and 12 months (P < 0.0001). Levels of insulin-like growth factor-I an index of nutritional status, significantly increased at 3, 6, and 12 months compared with the baseline value (P < 0.001). This therapy was effective for all patients. Serious complications were not seen after this treatment, although such minor complications as fever and flank pain were observed within the first week after the procedure. Our internal treatment with TAE is a safe and effective procedure that has resulted in improvement in the quality of life and nutritional status of patients with ADPKD. © 2002 by the National Kidney Foundation, Inc. INDEX WORDS: Renal contraction therapy; transcatheter arterial embolization (TAE); renal transcatheter arterial embolization (TAE); autosomal dominant polycystic kidney disease (ADPKD); dialysis patient; intravascular coil.
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S RENAL FUNCTION deteriorates, computed tomographic and angiographic studies have clearly shown that overall renal mass and renal artery size usually diminish in patients with chronic renal failure. However, renal size of patients with autosomal dominant polycystic kidney disease (ADPKD) usually continues to increase, even after the initiation of dialysis therapy, because numerous cysts replace renal mass. Moreover, renal arteries supplying these kidneys also develop markedly. In Western countries, many patients with ADPKD undergo renal transplantation soon after the initiation of dialysis therapy, and, if necessary, the enlarged kidney is nephrectomized before transplantation. For this reason, complications from enlarged kidneys in patients with ADPKD are less of a clinical issue in the West than in Japan, where renal transplantation is performed less frequently. With little hope of receiving a replacement organ, many Japanese patients with ADPKD experience anatomic problems related to nephromegaly. Especially frequent are such gastrointestinal complications as ischemic colitis, ileus, and intestinal perforation. Attempted methods to reduce the size of en-
larged kidneys have included needle aspiration and sclerosing of renal cysts,1-3 surgical and laparoscopic fenestration,1,3-6 and surgical and laparoscopic nephrectomy.6-10 Surgical nephrectomy has been performed on many patients in Japan. Although sufficient data for analysis are not available, the prognosis frequently has been suboptimal, and there clearly is a need to develop a more effective therapy. In 1999, we reported a successful case of a patient on long-term hemodialysis therapy in whom transcatheter arterial embolization (TAE) of the renal arteries reduced the size of markedly enlarged kidneys. From October 1996 to October 2000, renal contraction therapy using TAE was performed on 64 patients on dialysis therapy
From the Kidney Center, Toranomon Hospital, Tokyo, Japan. Received July 11, 2000; accepted in revised form September 28, 2001. Address reprint requests to Yoshifumi Ubara, MD, Kidney Center, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo 105-8470, Japan. E-mail: [email protected] © 2002 by the National Kidney Foundation, Inc. 0272-6386/02/3903-0014$35.00/0 doi:10.1053/ajkd.2002.31407
American Journal of Kidney Diseases, Vol 39, No 3 (March), 2002: pp 571-579
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with enlarged and/or hemorrhagic polycystic kidneys. Data for these patients are presented in this report. PATIENTS AND METHODS
Patients The 64 patients included 39 men and 25 women aged 47 to 72 years (mean, 58 ⫾ 8 [SD] years). Patients had been on dialysis therapy for 0 to 17 years (mean, 6 ⫾ 5 years). Six of 64 patients were from our institute, and the other 58 patients were introduced for this new treatment from 49 dialysis centers in Japan. Based on our objective criteria, we selected patients with ADPKD on maintenance dialysis therapy who strongly desired renal TAE because of compression symptoms related to enlarged kidneys. Patients gave their consent after being fully informed about the new procedure, including its frequent complications of fever and pain. Because patients eventually become anuric after renal TAE, this therapy was not administered until the patient’s urinary volume decreased to less than 500 mL/d and anuria or oliguria developed. However, in one patient with urinary volume of 800 to 1,000 mL/d who was undergoing hemodialysis three times weekly, we performed renal TAE to provide symptomatic relief. One patient was started on continuous ambulatory peritoneal dialysis (CAPD) therapy, and the other 63 patients were continued on hemodialysis therapy. Fifty-three of 64 patients had progressive abdominal distension, dysphagia, constipation, and diminished oral intake. The other 11 patients underwent TAE mainly to treat bleeding. In patients with only limited bleeding, selective renal arterial embolization was performed, and urinary output thus
was maintained. In less fortunate patients with multiple bleeding sites, renal TAE was performed extensively, resulting in anuria. Three patients who had undergone unilateral nephrectomy because of renal bleeding or renal transplantation also began to bleed in the contralateral kidney. Two patients had a history of extensive abdominal surgery because of intestinal or duodenal perforation. This treatment was performed for a patient who had undergone 5 years of CAPD therapy with progressive difficulty draining the dialysate fluid into the peritoneal cavity. Eleven patients had marked hepatomegaly caused by multiple hepatic cysts.
Interventional Procedure of Renal TAE The diagnosis of ADPKD was established by computed tomography, magnetic resonance imaging, and ultrasonography. We used Seldinger’s technique to perform renal angiography. After local anesthesia was achieved, the femoral artery was cannulated, and selective angiography of the renal artery was performed using a 5 F shepherd hook catheter (Cathex; Shibuya, Tokyo, Japan). Patients were divided into three stages according to the material used for embolization. Stage 1. TAE using a stainless steel coil was performed on 12 patients from October 1996 to June 1999. This coil was used to obstruct the large renal arterial branches located proximally (Fig 1). After the selective shepherd hook catheter was removed, a 5 F multipurpose catheter (Cathex) was placed over the guide wire (Terumo; Shibuya) into the proximal branches of the renal artery. The guide-wire catheter was removed and used again to push the stainless coil (Cook Group Co, Bloomington, IN) past the tip of the catheter. All coils were 0.035 inch in diameter and 1, 2, or 3 cm in length.
Fig 1. (A) Angiography before renal TAE shows narrowed and stretched renal arteries of ADPKD. Stainless steel coils (arrow) are placed in a peripheral portion of the main renal artery. (B) Angiography soon after TAE using a steel coil (arrow). (C) Angiography 6 months after TAE shows many recanalized branches. (Arrow indicates location of inserted coils.)
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In three patients with suboptimal results, many branches were recanalized, prompting us to repeat renal TAE twice more at 6-month intervals (Fig 1). In these procedures, we found that catheters usually would not advance into the peripheral renal arteries because proximal renal arteries were obstructed incompletely by coils. Additional coils were placed on the more proximal renal arteries; however, these could not be inserted safely or fully. Stage 2. In expectation of a greater effect and improved safety, we used a platinum microcoil (TornadoR [Cook Group Co], DiamondR [Boston Scientific, Boston, MA], and Trufill occlusion coil [Cordis, Miami, FL]) in 10 patients from June 1999 to September 1999. This coil was smaller than the steel coil and used to obstruct peripheral renal artery branches (Figs 2 and 3). A 3 F microcatheter (Micro FerretR; Cook Group Co; or RenegadeR; Boston Scientific) was inserted into the peripheral smaller branches of the renal artery through an intra–shepherd hook catheter under the lead of the guide wire. The guide-wire catheter was removed, and the platinum microcoil was pushed by the pusher (Trupush R; Cordis). Coils were 0.018 inch in diameter and 4 to 10 cm in length. Although recanalization was observed in two patients, TAE was more effective on these patients than the three stage-1 patients with recanalization, and the repeated procedure could be performed safely and easily because proximal renal arteries were reserved. Stage 3. For stage 3, we applied a gelatin sponge close to the platinum microcoil. This method was used in 42 patients from October 1999 to December 2000. Results were better than those obtained in stage 2. The additional gelatin sponge apparently was effective for most of the smaller renal arterial branches that could not be obstructed by microcoils. In the first five patients, renal TAE was performed in each kidney after an interval of 2 weeks. However, because two patients experienced hemorrhage in the contralateral kidney after renal TAE on one side, renal TAE was performed simultaneously on both sides in the remaining 59 patients.
Fig 2. (A) Microcoils (arrows) are placed in peripheral branches of the renal artery. (B) Angiography after TAE shows multiple linear branches obstructed by many microcoils (arrows).
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Five to 23 coils (mean, 10.1 ⫾ 5.8 coils) were used in group 1; 24 to 40 coils (mean, 30.0 ⫾ 5.9 coils), in group 2; and 16 to 56 coils (mean, 31.2 ⫾ 11.2 coils), in group 3.
Indices of Effectiveness After Renal TAE The renal shrinkage rate was studied by the following three indices. 1. Renal size was calculated as volume by computed tomography using the formula for an ellipsoid: a ⫻ b ⫻ c ⫻ /6, where a is the maximum length of the kidney and b and c are the maximum widths in the two transverse dimensions (Fig 4). Kidney size was determined 3, 6, and 12 months after ablation therapy, and the fractional reduction was compared with the pretreatment value ([size after renal TAE/size before renal TAE] ⫻ 100%) was calculated as an average for every pair of kidneys. 2. Abdominal circumference was measured at the position of the umbilicus (Fig 5) because maximal abdominal circumference may not be an accurate index of renal volume in patients with hepatomegaly. The change in abdominal circumference after 3, 6, and 12 months was obtained by subtracting the value for each period after TAE from the value before therapy. 3. Standard body weight was estimated as dry weight measured at the end of the hemodialysis session, provided that normal control of blood pressure and edema was obtained in the patient (Fig 6). Dry weight was determined 3, 6, and 12 months after TAE, and the change from pretreatment value was calculated. 4. Laboratory data for hematocrit, serum albumin, lactate dehydrogenase, potassium, phosphate, total cholesterol, C-reactive protein, renin concentration, endogenous erythropoietin, and insulin-like growth factor-I were measured before and after TAE. We analyzed these data only for the 64 patients followed up longer than 3 months.
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Fig 3. (A) Computed tomography before renal TAE shows the markedly enlarged kidneys of a patient with ADPKD (same case as Fig 2). (B) Computed tomography 12 months after TAE using microcoils shows a marked decrease in kidney size.
Fig 4. Renal sizes at 3, 6, and 12 months after TAE decreased significantly (*P < 0.0001) compared with preintervention. Renal size continued to decrease. Results presented as mean ⴞ SD.
Fig 5. Decrease in abdominal circumference after renal TAE. Abdominal circumference continued to decrease significantly at 3, 6, and 12 months (*P < 0.0001) compared with preintervention. Results presented as mean ⴞ SD.
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Dry weight. Dry weight was 59.1 ⫾ 9.9 kg (range, 39 to 80 kg) before renal TAE and decreased by 3.1 ⫾ 1.9, 3.2 ⫾ 2.4, and 2.6 ⫾ 2.1 kg after 3, 6, and 12 months, respectively (P ⬍ 0.0001) compared with the preinterventional value (Fig 6). A mild but significant increase in dry weight was seen between 6 versus 12 months (P ⬍ 0.05). Dry weight continued to decrease until 6 months after TAE, then began to increase as patients’ appetites improved.
Fig 6. Reductions in dry weight were seen 3, 6, and 12 months after TAE (*P < 0.0001) compared with the value before renal TAE. Dry weight continued to decrease until 6 months after TAE, then began to increase. Results presented as mean ⴞ SD.
Economic Justification Interventional radiology therapy using coils is reimbursed by the national health insurance system in Japan and has been applied to intracranial aneurysms, hepatocellular carcinoma, and many other diseases. Although renal TAE for ADPKD is expensive, it is an imperative measure for patient survival and thus also is reimbursed.
Statistical Analysis Statistical analysis was performed using Statview 5.0 for Macintosh (Statview-J.S.O. PPC, SAS Institute Inc, 19921998). Results are expressed as mean ⫾ SD. Comparisons between values before and after renal TAE were performed by t-test for paired data. Differences with P less than 0.05 are regarded as significant.
RESULTS
Renal Shrinkage Rate Results of the three groups overall are as follows. Renal size. Renal size was 2,068 ⫾ 1,972 cm3 (range, 578 to 8,803 cm3) before renal TAE and decreased to 73.8% ⫾ 12.0% (P ⬍ 0.0001), 61.7% ⫾ 14.7% (P ⬍ 0.0001), and 53.4% ⫾ 11.6% (P ⬍ 0.0001) of the preinterventional value at 3, 6, and 12 months after therapy, respectively(Figs 3 and 4). Abdominal circumference. Abdominal circumference was 93.7 ⫾ 9.2 cm (range, 72 to 115 cm) before renal TAE and decreased by 10.1 ⫾ 4.6, 11.5 ⫾ 4.8, and 11.8 ⫾ 4.3 cm after 3, 6, and 12 months, respectively (P ⬍ 0.0001) compared with the preinterventional value (Fig 5).
Subjective Symptoms Before objective confirmation of diminution of renal size by diagnostic imaging, the majority of patients began to experience relief of symptoms within 1 to 2 weeks, and all patients experienced relief of symptoms within 1 month. Relief was achieved even in patients with severe hepatomegaly. On physical examination, the hard elastic and rugged kidneys became soft and sponge-like, suggesting that cystic fluid had begun to decrease, even at this early stage. Bowel movements became active, and most patients no longer required laxatives. Macrohematuria disappeared in the 11 patients who had shown this symptom. Relief was obtained in 1 patient on CAPD therapy, and CAPD therapy could be continued. Hematologic Findings Hematocrits before TAE and at 3, 6, and 12 months after TAE were 29.4% ⫾ 6.0%, 35.1% ⫾ 5.1%, 36.2% ⫾ 5.4%, and 36.2% ⫾ 5.3%, respectively. All postinterventional values were significantly (P ⬍ 0.0001) greater than before therapy. Genetic recombinant erythropoietin derivatives were administered to 58% of patients before therapy and 30% of patients 6 months after therapy. Endogenous erythropoietin values before TAE and at 3, 6, and 12 months after TAE were 77.8 ⫾ 140.6, 89.7 ⫾ 82.0, 99.4 ⫾ 120.0, and 124.0 ⫾ 206 mU/mL, respectively. No difference was seen among these values. C-Reactive protein levels increased from 0.9 ⫾ 0.6 mg/dL to a maximum value of 18.1 ⫾ 6.0 mg/dL after 3 days (P ⬍ 0.0001) and decreased to 1.7 ⫾ 1.2 mg/dL after 19 days. Lactate dehydrogenase levels increased significantly from 141 ⫾ 19 to 229 ⫾ 52 IU/L after 3 days (P ⬍ 0.0001) and decreased to 146 ⫾ 19 IU/L after 19
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days. Serum potassium and phosphate levels were not significantly elevated after TAE. Despite renal arterial embolization, renovascular hypertension did not develop. Serum renin concentration (normal, 3.4 to 21.3 pg/mL) was 5.0 ⫾ 7.6 pg/mL before TAE and 7.3 ⫾ 12.7 pg/mL at 3 months, 9.4 ⫾ 13.3 pg/mL at 6 months, and 10.4 ⫾ 14.1 pg/mL at 12 months after TAE. No difference was seen among these values. Nutritional Status Levels of insulin-like growth factor-1, an index of nutritional status, increased significantly to 257.6 ⫾ 108.1 ng/mL (range, ⬃113 to 489 ng/mL), 282.0 ⫾ 118.0 ng/mL (range, ⬃122 to 571 ng/mL), and 273.8 ⫾ 125.4 ng/mL (range, ⬃126 to 664 ng/mL) after 3, 6, and 12 months, respectively (P ⱕ 0.001) compared with the pretreatment value of 205.5 ⫾ 74.2 ng/mL (range, ⬃68 to 435 ng/mL). Serum albumin levels were 3.02 ⫾ 0.34 g/dL (range, ⬃2.0 to 3.6 g/dL) before TAE and 3.20 ⫾ 0.32 g/dL (range, ⬃2.3 to 3.8 g/dL) at 3 months, 3.30 ⫾ 0.30 g/dL (range, ⬃2.7 to 3.9 g/dL) at 6 months, and 3.40 ⫾ 0.31 g/dL (range, ⬃3.0 to 3.9 g/dL) at 12 months after TAE. All serum albumin levels after TAE were significantly (P ⱕ 0.001) greater than the preinterventional level. Total cholesterol levels were 150.3 ⫾ 34.6 mg/dL (range, ⬃83 to 239 mg/dL) before TAE and 163.2 ⫾ 40.6 mg/dL (range, ⬃100 to 248 mg/dL) at 3 months, 171.9 ⫾ 40.0 mg/dL (range, ⬃129 to 250 mg/dL) at 6 months, and 177.9 ⫾ 33.6 mg/dL (range, ⬃132 to 246 mg/dL) at 12 months after TAE. All postinterventional values were significantly (P ⱕ 0.001) greater than the value before therapy. Complications After Renal TAE Severe flank pain occurred 1 hour after the procedure in all patients. Pain peaked the next day and subsided by day 5 in the majority of patients. For the first 14 patients, nonsteroidal anti-inflammatory drugs (NSAIDs) and/or pentazocine were administered to control the pain. For the remaining 50 patients, an epidural catheter was inserted into the 10th or 11th thoracic spine. From the start of TAE, local anesthesia was achieved using 0.24% bupivacaine and 1% lidocaine injected continuously and titrated to the
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degree of pain. NSAIDs and/or pentazocine were added in case of severe pain. The catheter was removed approximately 4 days after TAE. Fever occurred within 6 hours after the start of TAE in all patients. Temperatures increased to a maximum of 38.3°C ⫾ 0.7°C and persisted for 8.2 ⫾ 4.3 days. All patients were treated with antibiotics, and NSAIDs were administered to control fever. One patient remained febrile for 28 days. None of the patients developed new renal cyst infections, and there were no relapses in patients with a history of infection. No major complications have occurred. Technical Points Several technical issues are crucial for the successful performance of renal TAE. 1. Renal TAE was especially effective in patients older than 60 years and/or those with severe arteriosclerosis. However, when performed on patients younger than 60 years and/or patients with mild arteriosclerosis, many branches of the renal artery became recanalized soon after TAE, leading to poorer results. Because renal arteries in the latter patients are more elastic, they can swell easily in width even after TAE, thus leading to recanalization. To avoid this, coils at first were inserted into smaller branches of the renal arteries as peripherally as possible. 2. Centrally located renal arteries should not be embolized at first because this makes repeated renal TAE difficult to perform. 3. It is desirable to embolize as many arterial branches of both kidneys as possible, including renal capsular arteries, all at once because blood flow may rush into the remaining arteries, increasing the risk for hemorrhage secondary to volume overload. 4. Great care should be taken not to drop the coil into the abdominal aorta. DISCUSSION
According to a survey by the Japanese Society for Dialysis Therapy, 206,134 patients in Japan were on dialysis therapy in 2000. Patients with ADPKD totaled 6,404, accounting for 3.2% of all dialysis patients that year.11 Intracranial aneurysm rupture is a well-known complication of
RENAL CONTRACTION THERAPY FOR ADPKD
ADPKD, but symptoms even more particular to ADPKD are caused by compression of the digestive tract, lungs, and heart by enlarged kidneys. These symptoms include dysphagia, gastroesophageal reflux, early satiety, severe changes in bowel habits, dyspnea, and orthopnea. All of them may result in death from ischemic colitis, peritonitis with intestinal perforation, or cachexia. To reduce the size of enlarged kidneys, several methods have been reported: (1) needle aspiration of the cyst, followed by injection of sclerosing agents; (2) cyst decompression surgery; (3) laparoscopic fenestration; (4) laparoscopic nephrectomy; and (5) surgical nephrectomy. After aspiration of cystic fluid through ultrasound guidance, such sclerosing agents as 95% ethanol and minocycline are injected into the cysts.1,2 Serious complications with this method include perirenal hemorrhage, arteriovenous fistula formation, and infection.3 The effect is temporary, and recurrence has been reported in 6 of 11 patients within 3 to 6 months.1 However, no study of hemodialysis patients with enlarged kidneys has been reported. Many studies have shown that surgical decompression is effective in relieving pain. This method is primarily used before the initiation of hemodialysis therapy. Such complications as upper urinary collecting system injury, urinary tract infection, bleeding, incisional hernia, and smallbowel obstruction have been reported.1,4,5 Cysts can be fenestrated using laparoscopic techniques. Although short-term results of the laparoscopic method suggest that it is safe and effective, the long-term effect remains unknown. Laparoscopy is contraindicated in patients with a bleeding diathesis or history of peritonitis or extensive intestinal surgery.3,6 A report was recently published on nine symptomatic patients with nephromegaly who underwent laparoscopic nephrectomy.6,7 Expected benefits of this approach were minimal intraoperative blood loss, minimal postoperative pain, brief hospitalization, and rapid convalescence. However, such complications as the need for blood transfusion and venacavotomy were encountered. The fifth method, surgical nephrectomy, is usually indicated for patients with a short duration of hemodialysis therapy before renal trans-
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plantation.8,9 Nephrectomy usually is unilateral, and removal of bilateral kidneys is very rare. Surgeons frequently have technical difficulties removing the markedly enlarged kidneys of patients on long-term hemodialysis therapy. The literature on these surgical cases is spare.10 These five methods may be called external treatments because they are performed by a transabdominal approach. Moreover, these methods usually are not safe. A safer and more effective therapy needs to be developed. In 1999, we reported a case in which the size of an enlarged kidney could be reduced by obstructing renal arteries.12 We call this method internal treatment, or renal TAE. TAE has been a popular therapy for hepatocellular carcinoma because vessels that feed this cancer are highly dependent on the hepatic artery. Kidneys of patients with ADPKD mostly continue to grow, even after the initiation of dialysis therapy, because renal parenchyma is replaced by numerous cysts. On angiographic study, renal arteries become large, prolonged, and well developed in proportion to the size of the kidney, with peripheral branches encircling the cysts. Doppler ultrasonography shows well-developed vascularity along cyst walls (Fig 7). On histological examination, the remaining interstitium between cysts is replaced by fibrous tissue, but remains well vascularized (Fig 8). As renal failure progresses, the role of renal arteries appears to shift from supporting renal function to supplying fluid to multiple renal cysts. In this disease, the mechanism of angiogenesis might develop and
Fig 7. On Doppler ultrasonographic study, welldeveloped vascularity is observed along cyst walls.
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Fig 8. Histological examination of a kidney in a patient with ADPKD shows well-vascularized interstitium and multiple cysts. Abbreviations: A, small renal artery; V, small renal vein; C, renal cyst. (Hematoxylin eosin staining, original magnification ⴛ 100.)
provide a feeding artery to the cysts. Thus, we hypothesized that procedures designed to obstruct the well-developed renal arteries may lead to shrinkage of renal cysts. TAE therapy first was reported by Harley et al13 in 1980 for a patient with ADPKD. Although the procedure was effective in controlling intractable hemorrhage, the investigators did not emphasize an effect in lessening renal mass. Since then, this therapy has been used solely to treat renal hemorrhage caused by trauma, arteriovenous fistula formation, and polyarteritis nodosa.14-16 Since our first report, we have performed this therapy on 64 patients and obtained renal shrinkage in almost all of them. In contrast to reported outcomes using external methods, our patients have not experienced major complications. With diminution of renal mass, many symptoms disappeared, improving both quality of life and nutritional status. This therapy is expected to become even more effective as embolization materials and techniques are improved further in the future. ACKNOWLEDGMENT The authors thank Professor Masahiko Ishibashi, College of Environmental Health, Azabu University, and Yoshiki Nishizawa, Second Department of Internal Medicine, Osaka City University, for advice throughout the course of this study.
REFERENCES 1. Bennett WM, Elzinga L, Golper TA, Barry JM: Reduction of cyst volume for symptomatic management of autosomal dominant polycystic kidney disease. J Urol 137:620622, 1987 2. Uemasu J, Fujiwara M, Munemura C, Tokumoto A, Kawasaki H: Effects of topical instillation of minocycline hydrochloride on cyst size and renal function in polycystic kidney disease. Clin Nephrol 39:140-144, 1993 3. Segura TW, King BF, Towsey SG, Martin P, Zincke H: Chronic pain and its medical and surgical management in renal cystic diseases, in Watson ML, Torres VE (eds): Polycystic Kidney Disease. Oxford, NY, Oxford, 1996, pp 462-480 4. Elzinga LW, Barry JM, Bennett WM: Surgery in the management of autosomal dominant polycystic kidney disease. Am J Kidney Dis 19:89-92, 1992 5. Elzinga LW, Barry JM, Torres VE, Zincke H, Wahner HW, Swan S, Bennett WM: Cyst decompression surgery for autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2:219-226, 1992 6. Elashry OM, Nakada SY, Wolf JS, McDougall EM, Clayman RV: Laparoscopy for adult polycystic kidney disease: A promising alternative. Am J Kidney Dis 27:224-233, 1996 7. Dunn MD, Portis AJ, Elbahnsy AM, Shalhav AL, Rothstein M, McDougall EM, Clayman RV: Laparoscopic nephrectomy in patients with end-stage renal disease and autosomal dominant polycystic kidney disease. Am J Kidney Dis 35:720-725, 2000 8. Mandelsson DC, Harding ME, Cardella CJ, Cook GT, Uldall PR: Management of end-stage autosomal dominant polycystic kidney disease with hemodialysis and transplantation. Clin Nephrol 30:315-319, 1988 9. Cassuto-Viguier E, Quintens H, Chevallier D, Derrier
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M, Jambou P, Toubol J, Duplay H: Transplantation and nephrectomy in autosomal dominant polycystic disease. Clin Nephrol 36:105-106, 1991 10. Milutinovic J: Massive growth of kidneys in patients with autosomal polycystic kidney disease treated with chronic hemodialysis. Am J Kidney Dis 16:365-368, 1989 11. Akiba T: An Overview of Regular Dialysis Treatment in Japan (as of December 31, 2000). Tokyo, Japan, Japanese Society for Dialysis Therapy, 2000, pp 434-440 12. Ubara Y, Katori H, Tagami T, Tanaka T, Yokota M, Matsusita Y, Takemoto F, Imai T, Inoue S, Kuzuhara K, Hara S, Yamada A: Transcatheter renal arterial enbolization therapy on a patient with polycystic kidney disease on hemodialysis. Am J Kidney Dis 34:926-931, 1999
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13. Harley JD, Shen FH, Carter SJ: Transcatheter infarction of a polycystic kidney for control of recurrent hemorrhage. AJR Am J Roentgenol 134:818-820, 1980 14. Bookstein JJ, Goldstein HM: Successful management of post biopsy arteriovenous fistula with selective arterial embolization. Radiology 109:535-536, 1973 15. Silber SJ, Collins E, Clark R: Treatment of hemorrhage from renal trauma by angiographic injection of clot. J Urol 116:15-19, 1976 16. Sautter T, Trinkler FB, Susler T, Schopke W, Hauri D: Spontaneously perirenal hemorrhage after rupture of an aneurysm in a case of polyarteritis nodosa along with anuric renal failure. Urol Int 59:188-190, 1997
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S RENAL FUNCTION deteriorates, computed tomographic and angiographic studies have clearly shown that overall renal mass and renal artery size usually diminish in patients with chronic renal failure. However, renal size of patients with autosomal dominant polycystic kidney disease (ADPKD) usually continues to increase, even after the initiation of dialysis therapy, because numerous cysts replace renal mass. Moreover, renal arteries supplying these kidneys also develop markedly. In Western countries, many patients with ADPKD undergo renal transplantation soon after the initiation of dialysis therapy, and, if necessary, the enlarged kidney is nephrectomized before transplantation. For this reason, complications from enlarged kidneys in patients with ADPKD are less of a clinical issue in the West than in Japan, where renal transplantation is performed less frequently. With little hope of receiving a replacement organ, many Japanese patients with ADPKD experience anatomic problems related to nephromegaly. Especially frequent are such gastrointestinal complications as ischemic colitis, ileus, and intestinal perforation. Attempted methods to reduce the size of en-
larged kidneys have included needle aspiration and sclerosing of renal cysts,1-3 surgical and laparoscopic fenestration,1,3-6 and surgical and laparoscopic nephrectomy.6-10 Surgical nephrectomy has been performed on many patients in Japan. Although sufficient data for analysis are not available, the prognosis frequently has been suboptimal, and there clearly is a need to develop a more effective therapy. In 1999, we reported a successful case of a patient on long-term hemodialysis therapy in whom transcatheter arterial embolization (TAE) of the renal arteries reduced the size of markedly enlarged kidneys. From October 1996 to October 2000, renal contraction therapy using TAE was performed on 64 patients on dialysis therapy
From the Kidney Center, Toranomon Hospital, Tokyo, Japan. Received July 11, 2000; accepted in revised form September 28, 2001. Address reprint requests to Yoshifumi Ubara, MD, Kidney Center, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo 105-8470, Japan. E-mail: [email protected] © 2002 by the National Kidney Foundation, Inc. 0272-6386/02/3903-0014$35.00/0 doi:10.1053/ajkd.2002.31407
American Journal of Kidney Diseases, Vol 39, No 3 (March), 2002: pp 571-579
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with enlarged and/or hemorrhagic polycystic kidneys. Data for these patients are presented in this report. PATIENTS AND METHODS
Patients The 64 patients included 39 men and 25 women aged 47 to 72 years (mean, 58 ⫾ 8 [SD] years). Patients had been on dialysis therapy for 0 to 17 years (mean, 6 ⫾ 5 years). Six of 64 patients were from our institute, and the other 58 patients were introduced for this new treatment from 49 dialysis centers in Japan. Based on our objective criteria, we selected patients with ADPKD on maintenance dialysis therapy who strongly desired renal TAE because of compression symptoms related to enlarged kidneys. Patients gave their consent after being fully informed about the new procedure, including its frequent complications of fever and pain. Because patients eventually become anuric after renal TAE, this therapy was not administered until the patient’s urinary volume decreased to less than 500 mL/d and anuria or oliguria developed. However, in one patient with urinary volume of 800 to 1,000 mL/d who was undergoing hemodialysis three times weekly, we performed renal TAE to provide symptomatic relief. One patient was started on continuous ambulatory peritoneal dialysis (CAPD) therapy, and the other 63 patients were continued on hemodialysis therapy. Fifty-three of 64 patients had progressive abdominal distension, dysphagia, constipation, and diminished oral intake. The other 11 patients underwent TAE mainly to treat bleeding. In patients with only limited bleeding, selective renal arterial embolization was performed, and urinary output thus
was maintained. In less fortunate patients with multiple bleeding sites, renal TAE was performed extensively, resulting in anuria. Three patients who had undergone unilateral nephrectomy because of renal bleeding or renal transplantation also began to bleed in the contralateral kidney. Two patients had a history of extensive abdominal surgery because of intestinal or duodenal perforation. This treatment was performed for a patient who had undergone 5 years of CAPD therapy with progressive difficulty draining the dialysate fluid into the peritoneal cavity. Eleven patients had marked hepatomegaly caused by multiple hepatic cysts.
Interventional Procedure of Renal TAE The diagnosis of ADPKD was established by computed tomography, magnetic resonance imaging, and ultrasonography. We used Seldinger’s technique to perform renal angiography. After local anesthesia was achieved, the femoral artery was cannulated, and selective angiography of the renal artery was performed using a 5 F shepherd hook catheter (Cathex; Shibuya, Tokyo, Japan). Patients were divided into three stages according to the material used for embolization. Stage 1. TAE using a stainless steel coil was performed on 12 patients from October 1996 to June 1999. This coil was used to obstruct the large renal arterial branches located proximally (Fig 1). After the selective shepherd hook catheter was removed, a 5 F multipurpose catheter (Cathex) was placed over the guide wire (Terumo; Shibuya) into the proximal branches of the renal artery. The guide-wire catheter was removed and used again to push the stainless coil (Cook Group Co, Bloomington, IN) past the tip of the catheter. All coils were 0.035 inch in diameter and 1, 2, or 3 cm in length.
Fig 1. (A) Angiography before renal TAE shows narrowed and stretched renal arteries of ADPKD. Stainless steel coils (arrow) are placed in a peripheral portion of the main renal artery. (B) Angiography soon after TAE using a steel coil (arrow). (C) Angiography 6 months after TAE shows many recanalized branches. (Arrow indicates location of inserted coils.)
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In three patients with suboptimal results, many branches were recanalized, prompting us to repeat renal TAE twice more at 6-month intervals (Fig 1). In these procedures, we found that catheters usually would not advance into the peripheral renal arteries because proximal renal arteries were obstructed incompletely by coils. Additional coils were placed on the more proximal renal arteries; however, these could not be inserted safely or fully. Stage 2. In expectation of a greater effect and improved safety, we used a platinum microcoil (TornadoR [Cook Group Co], DiamondR [Boston Scientific, Boston, MA], and Trufill occlusion coil [Cordis, Miami, FL]) in 10 patients from June 1999 to September 1999. This coil was smaller than the steel coil and used to obstruct peripheral renal artery branches (Figs 2 and 3). A 3 F microcatheter (Micro FerretR; Cook Group Co; or RenegadeR; Boston Scientific) was inserted into the peripheral smaller branches of the renal artery through an intra–shepherd hook catheter under the lead of the guide wire. The guide-wire catheter was removed, and the platinum microcoil was pushed by the pusher (Trupush R; Cordis). Coils were 0.018 inch in diameter and 4 to 10 cm in length. Although recanalization was observed in two patients, TAE was more effective on these patients than the three stage-1 patients with recanalization, and the repeated procedure could be performed safely and easily because proximal renal arteries were reserved. Stage 3. For stage 3, we applied a gelatin sponge close to the platinum microcoil. This method was used in 42 patients from October 1999 to December 2000. Results were better than those obtained in stage 2. The additional gelatin sponge apparently was effective for most of the smaller renal arterial branches that could not be obstructed by microcoils. In the first five patients, renal TAE was performed in each kidney after an interval of 2 weeks. However, because two patients experienced hemorrhage in the contralateral kidney after renal TAE on one side, renal TAE was performed simultaneously on both sides in the remaining 59 patients.
Fig 2. (A) Microcoils (arrows) are placed in peripheral branches of the renal artery. (B) Angiography after TAE shows multiple linear branches obstructed by many microcoils (arrows).
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Five to 23 coils (mean, 10.1 ⫾ 5.8 coils) were used in group 1; 24 to 40 coils (mean, 30.0 ⫾ 5.9 coils), in group 2; and 16 to 56 coils (mean, 31.2 ⫾ 11.2 coils), in group 3.
Indices of Effectiveness After Renal TAE The renal shrinkage rate was studied by the following three indices. 1. Renal size was calculated as volume by computed tomography using the formula for an ellipsoid: a ⫻ b ⫻ c ⫻ /6, where a is the maximum length of the kidney and b and c are the maximum widths in the two transverse dimensions (Fig 4). Kidney size was determined 3, 6, and 12 months after ablation therapy, and the fractional reduction was compared with the pretreatment value ([size after renal TAE/size before renal TAE] ⫻ 100%) was calculated as an average for every pair of kidneys. 2. Abdominal circumference was measured at the position of the umbilicus (Fig 5) because maximal abdominal circumference may not be an accurate index of renal volume in patients with hepatomegaly. The change in abdominal circumference after 3, 6, and 12 months was obtained by subtracting the value for each period after TAE from the value before therapy. 3. Standard body weight was estimated as dry weight measured at the end of the hemodialysis session, provided that normal control of blood pressure and edema was obtained in the patient (Fig 6). Dry weight was determined 3, 6, and 12 months after TAE, and the change from pretreatment value was calculated. 4. Laboratory data for hematocrit, serum albumin, lactate dehydrogenase, potassium, phosphate, total cholesterol, C-reactive protein, renin concentration, endogenous erythropoietin, and insulin-like growth factor-I were measured before and after TAE. We analyzed these data only for the 64 patients followed up longer than 3 months.
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Fig 3. (A) Computed tomography before renal TAE shows the markedly enlarged kidneys of a patient with ADPKD (same case as Fig 2). (B) Computed tomography 12 months after TAE using microcoils shows a marked decrease in kidney size.
Fig 4. Renal sizes at 3, 6, and 12 months after TAE decreased significantly (*P < 0.0001) compared with preintervention. Renal size continued to decrease. Results presented as mean ⴞ SD.
Fig 5. Decrease in abdominal circumference after renal TAE. Abdominal circumference continued to decrease significantly at 3, 6, and 12 months (*P < 0.0001) compared with preintervention. Results presented as mean ⴞ SD.
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Dry weight. Dry weight was 59.1 ⫾ 9.9 kg (range, 39 to 80 kg) before renal TAE and decreased by 3.1 ⫾ 1.9, 3.2 ⫾ 2.4, and 2.6 ⫾ 2.1 kg after 3, 6, and 12 months, respectively (P ⬍ 0.0001) compared with the preinterventional value (Fig 6). A mild but significant increase in dry weight was seen between 6 versus 12 months (P ⬍ 0.05). Dry weight continued to decrease until 6 months after TAE, then began to increase as patients’ appetites improved.
Fig 6. Reductions in dry weight were seen 3, 6, and 12 months after TAE (*P < 0.0001) compared with the value before renal TAE. Dry weight continued to decrease until 6 months after TAE, then began to increase. Results presented as mean ⴞ SD.
Economic Justification Interventional radiology therapy using coils is reimbursed by the national health insurance system in Japan and has been applied to intracranial aneurysms, hepatocellular carcinoma, and many other diseases. Although renal TAE for ADPKD is expensive, it is an imperative measure for patient survival and thus also is reimbursed.
Statistical Analysis Statistical analysis was performed using Statview 5.0 for Macintosh (Statview-J.S.O. PPC, SAS Institute Inc, 19921998). Results are expressed as mean ⫾ SD. Comparisons between values before and after renal TAE were performed by t-test for paired data. Differences with P less than 0.05 are regarded as significant.
RESULTS
Renal Shrinkage Rate Results of the three groups overall are as follows. Renal size. Renal size was 2,068 ⫾ 1,972 cm3 (range, 578 to 8,803 cm3) before renal TAE and decreased to 73.8% ⫾ 12.0% (P ⬍ 0.0001), 61.7% ⫾ 14.7% (P ⬍ 0.0001), and 53.4% ⫾ 11.6% (P ⬍ 0.0001) of the preinterventional value at 3, 6, and 12 months after therapy, respectively(Figs 3 and 4). Abdominal circumference. Abdominal circumference was 93.7 ⫾ 9.2 cm (range, 72 to 115 cm) before renal TAE and decreased by 10.1 ⫾ 4.6, 11.5 ⫾ 4.8, and 11.8 ⫾ 4.3 cm after 3, 6, and 12 months, respectively (P ⬍ 0.0001) compared with the preinterventional value (Fig 5).
Subjective Symptoms Before objective confirmation of diminution of renal size by diagnostic imaging, the majority of patients began to experience relief of symptoms within 1 to 2 weeks, and all patients experienced relief of symptoms within 1 month. Relief was achieved even in patients with severe hepatomegaly. On physical examination, the hard elastic and rugged kidneys became soft and sponge-like, suggesting that cystic fluid had begun to decrease, even at this early stage. Bowel movements became active, and most patients no longer required laxatives. Macrohematuria disappeared in the 11 patients who had shown this symptom. Relief was obtained in 1 patient on CAPD therapy, and CAPD therapy could be continued. Hematologic Findings Hematocrits before TAE and at 3, 6, and 12 months after TAE were 29.4% ⫾ 6.0%, 35.1% ⫾ 5.1%, 36.2% ⫾ 5.4%, and 36.2% ⫾ 5.3%, respectively. All postinterventional values were significantly (P ⬍ 0.0001) greater than before therapy. Genetic recombinant erythropoietin derivatives were administered to 58% of patients before therapy and 30% of patients 6 months after therapy. Endogenous erythropoietin values before TAE and at 3, 6, and 12 months after TAE were 77.8 ⫾ 140.6, 89.7 ⫾ 82.0, 99.4 ⫾ 120.0, and 124.0 ⫾ 206 mU/mL, respectively. No difference was seen among these values. C-Reactive protein levels increased from 0.9 ⫾ 0.6 mg/dL to a maximum value of 18.1 ⫾ 6.0 mg/dL after 3 days (P ⬍ 0.0001) and decreased to 1.7 ⫾ 1.2 mg/dL after 19 days. Lactate dehydrogenase levels increased significantly from 141 ⫾ 19 to 229 ⫾ 52 IU/L after 3 days (P ⬍ 0.0001) and decreased to 146 ⫾ 19 IU/L after 19
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days. Serum potassium and phosphate levels were not significantly elevated after TAE. Despite renal arterial embolization, renovascular hypertension did not develop. Serum renin concentration (normal, 3.4 to 21.3 pg/mL) was 5.0 ⫾ 7.6 pg/mL before TAE and 7.3 ⫾ 12.7 pg/mL at 3 months, 9.4 ⫾ 13.3 pg/mL at 6 months, and 10.4 ⫾ 14.1 pg/mL at 12 months after TAE. No difference was seen among these values. Nutritional Status Levels of insulin-like growth factor-1, an index of nutritional status, increased significantly to 257.6 ⫾ 108.1 ng/mL (range, ⬃113 to 489 ng/mL), 282.0 ⫾ 118.0 ng/mL (range, ⬃122 to 571 ng/mL), and 273.8 ⫾ 125.4 ng/mL (range, ⬃126 to 664 ng/mL) after 3, 6, and 12 months, respectively (P ⱕ 0.001) compared with the pretreatment value of 205.5 ⫾ 74.2 ng/mL (range, ⬃68 to 435 ng/mL). Serum albumin levels were 3.02 ⫾ 0.34 g/dL (range, ⬃2.0 to 3.6 g/dL) before TAE and 3.20 ⫾ 0.32 g/dL (range, ⬃2.3 to 3.8 g/dL) at 3 months, 3.30 ⫾ 0.30 g/dL (range, ⬃2.7 to 3.9 g/dL) at 6 months, and 3.40 ⫾ 0.31 g/dL (range, ⬃3.0 to 3.9 g/dL) at 12 months after TAE. All serum albumin levels after TAE were significantly (P ⱕ 0.001) greater than the preinterventional level. Total cholesterol levels were 150.3 ⫾ 34.6 mg/dL (range, ⬃83 to 239 mg/dL) before TAE and 163.2 ⫾ 40.6 mg/dL (range, ⬃100 to 248 mg/dL) at 3 months, 171.9 ⫾ 40.0 mg/dL (range, ⬃129 to 250 mg/dL) at 6 months, and 177.9 ⫾ 33.6 mg/dL (range, ⬃132 to 246 mg/dL) at 12 months after TAE. All postinterventional values were significantly (P ⱕ 0.001) greater than the value before therapy. Complications After Renal TAE Severe flank pain occurred 1 hour after the procedure in all patients. Pain peaked the next day and subsided by day 5 in the majority of patients. For the first 14 patients, nonsteroidal anti-inflammatory drugs (NSAIDs) and/or pentazocine were administered to control the pain. For the remaining 50 patients, an epidural catheter was inserted into the 10th or 11th thoracic spine. From the start of TAE, local anesthesia was achieved using 0.24% bupivacaine and 1% lidocaine injected continuously and titrated to the
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degree of pain. NSAIDs and/or pentazocine were added in case of severe pain. The catheter was removed approximately 4 days after TAE. Fever occurred within 6 hours after the start of TAE in all patients. Temperatures increased to a maximum of 38.3°C ⫾ 0.7°C and persisted for 8.2 ⫾ 4.3 days. All patients were treated with antibiotics, and NSAIDs were administered to control fever. One patient remained febrile for 28 days. None of the patients developed new renal cyst infections, and there were no relapses in patients with a history of infection. No major complications have occurred. Technical Points Several technical issues are crucial for the successful performance of renal TAE. 1. Renal TAE was especially effective in patients older than 60 years and/or those with severe arteriosclerosis. However, when performed on patients younger than 60 years and/or patients with mild arteriosclerosis, many branches of the renal artery became recanalized soon after TAE, leading to poorer results. Because renal arteries in the latter patients are more elastic, they can swell easily in width even after TAE, thus leading to recanalization. To avoid this, coils at first were inserted into smaller branches of the renal arteries as peripherally as possible. 2. Centrally located renal arteries should not be embolized at first because this makes repeated renal TAE difficult to perform. 3. It is desirable to embolize as many arterial branches of both kidneys as possible, including renal capsular arteries, all at once because blood flow may rush into the remaining arteries, increasing the risk for hemorrhage secondary to volume overload. 4. Great care should be taken not to drop the coil into the abdominal aorta. DISCUSSION
According to a survey by the Japanese Society for Dialysis Therapy, 206,134 patients in Japan were on dialysis therapy in 2000. Patients with ADPKD totaled 6,404, accounting for 3.2% of all dialysis patients that year.11 Intracranial aneurysm rupture is a well-known complication of
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ADPKD, but symptoms even more particular to ADPKD are caused by compression of the digestive tract, lungs, and heart by enlarged kidneys. These symptoms include dysphagia, gastroesophageal reflux, early satiety, severe changes in bowel habits, dyspnea, and orthopnea. All of them may result in death from ischemic colitis, peritonitis with intestinal perforation, or cachexia. To reduce the size of enlarged kidneys, several methods have been reported: (1) needle aspiration of the cyst, followed by injection of sclerosing agents; (2) cyst decompression surgery; (3) laparoscopic fenestration; (4) laparoscopic nephrectomy; and (5) surgical nephrectomy. After aspiration of cystic fluid through ultrasound guidance, such sclerosing agents as 95% ethanol and minocycline are injected into the cysts.1,2 Serious complications with this method include perirenal hemorrhage, arteriovenous fistula formation, and infection.3 The effect is temporary, and recurrence has been reported in 6 of 11 patients within 3 to 6 months.1 However, no study of hemodialysis patients with enlarged kidneys has been reported. Many studies have shown that surgical decompression is effective in relieving pain. This method is primarily used before the initiation of hemodialysis therapy. Such complications as upper urinary collecting system injury, urinary tract infection, bleeding, incisional hernia, and smallbowel obstruction have been reported.1,4,5 Cysts can be fenestrated using laparoscopic techniques. Although short-term results of the laparoscopic method suggest that it is safe and effective, the long-term effect remains unknown. Laparoscopy is contraindicated in patients with a bleeding diathesis or history of peritonitis or extensive intestinal surgery.3,6 A report was recently published on nine symptomatic patients with nephromegaly who underwent laparoscopic nephrectomy.6,7 Expected benefits of this approach were minimal intraoperative blood loss, minimal postoperative pain, brief hospitalization, and rapid convalescence. However, such complications as the need for blood transfusion and venacavotomy were encountered. The fifth method, surgical nephrectomy, is usually indicated for patients with a short duration of hemodialysis therapy before renal trans-
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plantation.8,9 Nephrectomy usually is unilateral, and removal of bilateral kidneys is very rare. Surgeons frequently have technical difficulties removing the markedly enlarged kidneys of patients on long-term hemodialysis therapy. The literature on these surgical cases is spare.10 These five methods may be called external treatments because they are performed by a transabdominal approach. Moreover, these methods usually are not safe. A safer and more effective therapy needs to be developed. In 1999, we reported a case in which the size of an enlarged kidney could be reduced by obstructing renal arteries.12 We call this method internal treatment, or renal TAE. TAE has been a popular therapy for hepatocellular carcinoma because vessels that feed this cancer are highly dependent on the hepatic artery. Kidneys of patients with ADPKD mostly continue to grow, even after the initiation of dialysis therapy, because renal parenchyma is replaced by numerous cysts. On angiographic study, renal arteries become large, prolonged, and well developed in proportion to the size of the kidney, with peripheral branches encircling the cysts. Doppler ultrasonography shows well-developed vascularity along cyst walls (Fig 7). On histological examination, the remaining interstitium between cysts is replaced by fibrous tissue, but remains well vascularized (Fig 8). As renal failure progresses, the role of renal arteries appears to shift from supporting renal function to supplying fluid to multiple renal cysts. In this disease, the mechanism of angiogenesis might develop and
Fig 7. On Doppler ultrasonographic study, welldeveloped vascularity is observed along cyst walls.
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Fig 8. Histological examination of a kidney in a patient with ADPKD shows well-vascularized interstitium and multiple cysts. Abbreviations: A, small renal artery; V, small renal vein; C, renal cyst. (Hematoxylin eosin staining, original magnification ⴛ 100.)
provide a feeding artery to the cysts. Thus, we hypothesized that procedures designed to obstruct the well-developed renal arteries may lead to shrinkage of renal cysts. TAE therapy first was reported by Harley et al13 in 1980 for a patient with ADPKD. Although the procedure was effective in controlling intractable hemorrhage, the investigators did not emphasize an effect in lessening renal mass. Since then, this therapy has been used solely to treat renal hemorrhage caused by trauma, arteriovenous fistula formation, and polyarteritis nodosa.14-16 Since our first report, we have performed this therapy on 64 patients and obtained renal shrinkage in almost all of them. In contrast to reported outcomes using external methods, our patients have not experienced major complications. With diminution of renal mass, many symptoms disappeared, improving both quality of life and nutritional status. This therapy is expected to become even more effective as embolization materials and techniques are improved further in the future. ACKNOWLEDGMENT The authors thank Professor Masahiko Ishibashi, College of Environmental Health, Azabu University, and Yoshiki Nishizawa, Second Department of Internal Medicine, Osaka City University, for advice throughout the course of this study.
REFERENCES 1. Bennett WM, Elzinga L, Golper TA, Barry JM: Reduction of cyst volume for symptomatic management of autosomal dominant polycystic kidney disease. J Urol 137:620622, 1987 2. Uemasu J, Fujiwara M, Munemura C, Tokumoto A, Kawasaki H: Effects of topical instillation of minocycline hydrochloride on cyst size and renal function in polycystic kidney disease. Clin Nephrol 39:140-144, 1993 3. Segura TW, King BF, Towsey SG, Martin P, Zincke H: Chronic pain and its medical and surgical management in renal cystic diseases, in Watson ML, Torres VE (eds): Polycystic Kidney Disease. Oxford, NY, Oxford, 1996, pp 462-480 4. Elzinga LW, Barry JM, Bennett WM: Surgery in the management of autosomal dominant polycystic kidney disease. Am J Kidney Dis 19:89-92, 1992 5. Elzinga LW, Barry JM, Torres VE, Zincke H, Wahner HW, Swan S, Bennett WM: Cyst decompression surgery for autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2:219-226, 1992 6. Elashry OM, Nakada SY, Wolf JS, McDougall EM, Clayman RV: Laparoscopy for adult polycystic kidney disease: A promising alternative. Am J Kidney Dis 27:224-233, 1996 7. Dunn MD, Portis AJ, Elbahnsy AM, Shalhav AL, Rothstein M, McDougall EM, Clayman RV: Laparoscopic nephrectomy in patients with end-stage renal disease and autosomal dominant polycystic kidney disease. Am J Kidney Dis 35:720-725, 2000 8. Mandelsson DC, Harding ME, Cardella CJ, Cook GT, Uldall PR: Management of end-stage autosomal dominant polycystic kidney disease with hemodialysis and transplantation. Clin Nephrol 30:315-319, 1988 9. Cassuto-Viguier E, Quintens H, Chevallier D, Derrier
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M, Jambou P, Toubol J, Duplay H: Transplantation and nephrectomy in autosomal dominant polycystic disease. Clin Nephrol 36:105-106, 1991 10. Milutinovic J: Massive growth of kidneys in patients with autosomal polycystic kidney disease treated with chronic hemodialysis. Am J Kidney Dis 16:365-368, 1989 11. Akiba T: An Overview of Regular Dialysis Treatment in Japan (as of December 31, 2000). Tokyo, Japan, Japanese Society for Dialysis Therapy, 2000, pp 434-440 12. Ubara Y, Katori H, Tagami T, Tanaka T, Yokota M, Matsusita Y, Takemoto F, Imai T, Inoue S, Kuzuhara K, Hara S, Yamada A: Transcatheter renal arterial enbolization therapy on a patient with polycystic kidney disease on hemodialysis. Am J Kidney Dis 34:926-931, 1999
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13. Harley JD, Shen FH, Carter SJ: Transcatheter infarction of a polycystic kidney for control of recurrent hemorrhage. AJR Am J Roentgenol 134:818-820, 1980 14. Bookstein JJ, Goldstein HM: Successful management of post biopsy arteriovenous fistula with selective arterial embolization. Radiology 109:535-536, 1973 15. Silber SJ, Collins E, Clark R: Treatment of hemorrhage from renal trauma by angiographic injection of clot. J Urol 116:15-19, 1976 16. Sautter T, Trinkler FB, Susler T, Schopke W, Hauri D: Spontaneously perirenal hemorrhage after rupture of an aneurysm in a case of polyarteritis nodosa along with anuric renal failure. Urol Int 59:188-190, 1997