percutaneous transcatheter renal ablation with absolute ethanol for uncontrolled hypertension or...

Percutaneous Transcatheter Renal Ablation with Absolute Ethanol for Uncontrolled Hypertension or Nephrotic Syndrome: Results in 11 Patients with End-Stage Renal is ease'

Daniel H. Golwyn, Jr, MD PURPOSE: Retrospective review of authors' experience with per- William D. Routh, MD cutaneous transcatheter renal ablation in patients with uncon- Michael Y.M. Chen, MD trolled hypertension andlor nephrotic syndrome. William B. Lorentz, MD Raymond B. Dyer, MD MATERIALS AND METHODS: Between April 1987 and September

1995, renal ablation was performed on 11 patients aged 10 months to 21 years. All patients had end-stage renal disease (ESRD) with

Index Alcohol . Hypertension . uncontrolled hypertension (10 patients) andlor nephrotic syn- Kidney, interventional procedure drome (four patients). Uncontrolled hypertension was defined as Renal arteries, therapeutic blockade diastolic pressure greater than 90 mm Hg despite multidrug anti- JVIR 1997; 8:527-533 hypertensive therapy. Nephrotic syndrome was defined as protein-

uria exceeding 960 mg/m2 per day, serum albumin level less than 3 Abbreviation: ESRD = end-stage renal disease

g/dL, and generalized edema. Embolization was performed with absolute ethanol from a common femoral artery approach. In most cases, a balloon catheter was used to prevent alcohol reflux into the aorta or nontarget renal artery branches, such as the adrenal arteries. Angiographic stasis of contrast material in the renal arteries was the endpoint.

RESULTS: All patients experienced a postembolization syndrome of 3-5 days duration, clinically manifested by variable degrees of nausea, vomiting, fever, and pain. Long-term improvement in hypertension was observed in nine patients. Improvement in hypertension was defined as diastolic blood pressure below 90 mm Hg while the patient received the same or fewer antihypertensive medications. The four patients with nephrotic syndrome were cured of their proteinuria and edema.

CONCLUSIONS: Transarterial renal ablation with alcohol is effica- cious for treatment of uncontrolled hypertension and nephrotic

* From the Departments Of syndrome in patients with ESRD. The morbidity and mortality in (D.H.G., W.D.R., M.Y.M.C., R.B.D.) and Pediatrics (W,B,L,), Bowman Gray School our series were less than those reported for surgical nephrectomy. of Medicine, Medical Center Blvd, Wins- ton-Salem, NC 27157. From the 1996 SCVIR annual meeting. Received June 4, 1996; revision requested July 15; revision IN patients with end-stage soma1 dominant polycystic kidney received January 22, 1997; accepted disease (ESRD), nephrectomy may disease, andlor malignancy. Trans- January 23. Address correspondence be indicated for uncontrolled hyper- arterial renal ablation has been to D.H.G. tension, nephrotic syndrome, reflux successfully performed for the same o SCVIR, 1997. nephropathy, florid infection, auto- indications with the exception of

527

528 . Journal of Vascular and Interventional Radiology

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Table 1 Preablation Clinical Status and Method of Percutaneous Transcatheter Renal Ablation

Patient Age Primary Ablation No. (y)lSex Disease BUNlCr Indication Date Method

1 15/M Focal 5119.5 HTN uncontrolled x 2 years 10121193 Absolute alcohol-right 4.5 segmental (1701120 on three mL, left 4 mL; 4-mm glomerulo- antihypertensives) HA, N N angioplasty balloon sclerosis

2 10 mo/F Dysplastic 7114.1 HTN, failure to thrive 8/01/95 Absolute alcohol-right 2 mL, kidneys (1801130 on three left 3.5 mL; Simmons 1,

antihypertensives) Fierstein for accessory right renal artery

3 5/M Focal 2412.5 Nephrotic syndrome, HTN 02120195 (1st) absolute alcohol-right segmental (albumin 1.5 gldL) (135196 02/13/96 2.5 mL, left 2.5 mL; 4 mm glomerulo- on two antihypertensives) angioplasty balloon, 3 x sclerosis 5-mm coils

(2nd) right upper pole branch 2 mL, left main 5 mL; 5-F Cobra

4 4/F Focal 10918.4 Nephrotic syndrome, HTN 03101194 Absolute alcohol-right 1.3 segmental (albumin 1.5 gldL) (labile mL, left 1.6 mL; balloon glomerulo- BP on three occlusion sclerosis antihypertensives)

5 16/F Fanconi's 4013.0 HTN (1501115 on four 09/07/95 Absolute alcohol-right 3 mL, syndrome antihypertensives) left 6 mL; viper balloon (chronic rejection of transplant)

6 13/M Alport's 99111.1 HTN, seizures (labile BP on 04121187 Absolute alcohol-right 2 mL, syndrome three antihypertensives) left 3 mL; balloon occlusion,

small accessory branch to right lower pole not embolized

7 18/F SLE 4619.4 HTN, seizures (150190 on 08/22/88 Absolute alcohol-25 mL three antihypertensives) total, single renal arteries;

balloon occlusion 8 3/F Necrotizing 4111.0 Nephrotic syndrome, HTN 07126194 Absolute alcohol-right 10

glomerulo- (albumin 1.4 gldL) (1501100 mL, left 10 mL; balloon nephritis on four antihypertensives) occlusion

anasarca, CHF on ventilator

9 15/M Focal 4613.3 Nephrotic syndrome, HTN 06/05/91 Absolute alcohol-right 6 mL, segmental (albumin 1.4 gldL) (120190 accessory right 2 mL, left 6 glomerulo- on three antihypertensives) mL; balloon occlusion (PTA sclerosis (transplant 1119191) transplant vessel)

10 17/M Henoch-Schonlein 6314.2 HTN, CHF (1801120 on three 11130189 Absolute alcohol-right 1.5 purpura antihypertensives) mL, left 2 mL (chronic rejection of transplant)

11 21/F Focal 54113.1 HTN (1751110 on three 07118195 Absolute alcohol-right 6.5 segmental antihypertensives) mL, left 2 mL; angioplasty glomerulo- balloon sclerosis

Note.-BUN = blood urea nitrogen, CHF = congestive heart failure, Cr = creatinine, HTN = hypertension, HA = headache, NN =

nausealvomiting, SLE = systemic lupus erythematosus, PTA = percutaneous transluminal angioplasty.

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Table 2 Results and Clinical Follow-Up of Percutaneous Transcatheter Renal Ablation

Duration of Patient Age Postprocedural Hospitalization

No. (y)/Sex Course Complications Postprocedure Follow-up

1 1 5 N Pain, fever x 3 days None 7 days 20 months, 1601110, two antihypertensives, noncompliant

2 10 mo/F NN, fever x 3 days, Left CFA absent pulse 4 days 7 months, 94/40, 0 leukocytosis x 2 days, normal antihypertensives

a t follow-up 3* 5 N Pain, fever x 3 days, None 6 days-1st Rx 13 months, 110165, two

leukocytosis 28 days-2nd Rx antihypertensives, albumin recurrent HTN a t (HDPD 3.4 gldL, NS resolved 12 months difficulties)

4 4/F NNID, pain, fever x None 14 days (PD 16 months, 100160, three 10 days, difficulties) antihypertensives, albumin leukocytosis, labile 4.3 gIdL, NS resolved, BP transplant 6/94

5 16/F Pain, fever x 3 days None 3 days 4 months, 135180, two antihypertensives, rejected transplant not ablated

6 1 3 N NN, pain, fever x 3 None 10 days 91 months, 109163, one days (peritonitis) antihypertensive,

transplant 1190 7 18/F Pain x 8 days, fever None 12 days 87 months, 143179, four

x 3 days antihypertensives, transplant 7/89, childbirth (SVD) 4194, rejection with transplant nephrectomy 11/94

8 3/F Pain x 5 days, fever None 12 days 14 months, 110170, three antihypertensives, albumin 2.4 gldL, NS resolved

9 1 5 N Pain, fever x 4 days, None 4 days 47 months, 120185, two leukocytosis hypertensives, albumin 4.8

gIdL, NS resolved 10 1 7 N NN, pain, fever, None 17 days (HDPD 61 months, 130160, one

labile BP difficulties, antihypertensive, urinary retention) transplant 6182, rejected

6/89, 2nd transplant 6191 11 21/F NN, pain x 2 days, None 7 days 5 months, 108180, one

fever x 3 days antihypertensive

Note.-NNID = nausea, vomiting, diarrhea, HDPD = hemodialysis, peritoneal dialysis, NS = nephrotic syndrome, SVD = sponta- neous vaginal delivery. " Required 2nd ablation procedure.

malignancy and possibly infections (1-4). Some authors believe that there is an increased risk of abscess formation when renal ablation is performed in patients who have pyelonephritis or urinary tract infection (4,5).

Transarterial alcohol ablation of the kidneys is an alternative to surgical nephrectomy. We describe our experience with 11 consecutive patients undergoing renal ablation for uncontrolled hypertension and/ or nephrotic syndrome.

I MATERIALS AND METHODS Between April 1987 and Septem-

ber 1995, 11 patients underwent percutaneous transarterial renal ablation (Table 1). The patients ranged in age from 10 months to 21 years, with a median age of 14 years. All patients had ESRD with uncontrolled hypertension and/or nephrotic syndrome. Uncontrolled hypertension was defined as diastolic blood pressure greater than 90 mm Hg despite multidrug antihy-

pertensive therapy (6). Nephrotic syndrome was defined as proteinuria exceeding 960 mg/m2 per day, serum albumin level less than 3g/dL, and generalized edema. Two of the three patients who had previ- ously received renal transplants had chronic rejection. Only one patient had a functioning renal transplant at the time of ablation. The remaining 10 patients were dialysis dependent prior to treatment.

Although all patients were hy-

530 Journal of Vascular and Interventional Radiology

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a. b. Figure 1. Patient 3. (a) Note the small right upper pole branch arising from the inferior phrenic artery. An embolization coil is present in the main right renal artery. (b) There is partial recanalization of the left main renal artery with a parenchymal blush present.

pertensive (10 uncontrolled), the primary indication for renal ablation was nephrotic syndrome in four patients. All patients were referred by the pediatric nephrology service. Anesthesia was provided by the anesthesiology service in most cases. Five patients received general anesthesia. The remainder received local anesthesia and intravenous conscious sedation.

Abdominal aortography and selective renal arteriography were initially performed in all patients. A careful search was made for nontarget vessels, particularly adrenal and gonadal branches. After diag- nostic arteriography, the preferred method of ablation involved posi- tioning a 5-F balloon occlusion catheter (Medi-techBoston Scien- tific, Natick, MA) in the main renal artery. A manual test injection of contrast material was performed with the balloon inflated to assess the approximate volume of alcohol necessary to fill the arterial vasculature of the kidney. This volume of alcohol (usually between 0.5 and 2 mL) was then slowly injected manu- ally, with the balloon inflated. The balloon was deflated after 10 minutes, and a manual test injection of contrast material was performed to assess flow. Embolization was considered complete when there was angiographic stasis of

contrast material in the renal arteries without flow into peripheral branches. Angioplasty balloons (PEMT: Medi-tecWBoston Scientific) were used by some of the operators instead of balloon occlusion catheters. End-hole catheters (4-F Frier- stein and 5-F Simmons 1; Cook, Bloomington, IN) were used in the 10-month-old child due to the small size of the vessels embolized. Al- though the test injection method followed by injection of nonopacified alcohol has been reliable and safe. we have recently begun to mix the alcohol with metrizamide powder (0.3-0.5 g of metrizamide per mL of absolute alcohol) to allow fluoro- scopic visualization of the alcohol during embolization.

Clinical success in patients with uncontrolled hypertension was defined as diastolic blood pressure less than 90 mm Hg while the patient received the same or fewer antihypertensive medications (1).

The results of renal ablation and clinical follow-up are summarized in Table 2. In nine of 11 cases, all renal arteries were embolized. Patient 3 presented approximately 11 months after his initial renal ablation with peritonitis and diffi-

cult to control hypertension. Suc- cessful embolization of a recana- lized left main renal artery and a cryptic right upper pole branch (Figs 1 ,2 ) was performed almost 1 year after the original renal ablation. This child's nephrotic syndrome has not recurred, and his hypertension is again under control. Patient 6 had an accessory branch to the right lower pole, which was not embolized. This patient's hypertension has been well controlled without a second ablation procedure.

After the ablation, all patients experienced a postembolization syndrome lasting from 3-5 days. The syndrome was characterized by fever, nausea, vomiting, and pain. This is a normal sequela of alcohol ablation that has been well de- scribed in the literature (2,3). Pain was managed with intravenous morphine. No patients with active infection underwent renal ablation. When patients experienced spiking temperatures after embolization, they uniformly had urine and blood cultures obtained. The only organ- ism recovered was Staphylococcus epidermidis from one patient's peritoneal fluid. This patient had an indwelling peritoneal dialysis catheter and had recentlv been treated for peritonitis.

The length of hospitalization was prolonged in six patients because of dialysis access problems rather than postembolization complications.

Nephrotic syndrome resolved in the four patients with this disorder. Urine production (and therefore protein loss) ceased completely after renal ablation in all four patients.

Clinical success was achieved in nine of 11 patients. Six patients had documented sustained blood pressure control (diastolic < 90 mm Hg) while receiving fewer antihypertensive medications. Hyperten- sion was controlled in two patients by continuing similar medications and one patient remained normotensive without antihypertensive medication at 7-month follow-up. Patient 3 required a second ablation procedure to control recurrent hypertension due to residual viable

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Figure 2. Patient 3. (a) The native kidneys are shrunken and calcified. However, there is a small amount of remaining enhancing renal tissue in the right upper pole. (b) There is residual enhancing renal parenchyma in the left posterior midpole. Embolization coils in the main renal arteries are visible.

renal parenchyma. The patient's hypertension was controlled but his course may be considered a failure of the technique because he required repeated ablation. Patient 1 continued to have uncontrolled hypertension but was noncompliant with his medications, low-salt diet, and fluid restriction. The mean follow-up was 33 months with a range of 4-91 months.

Complications included an absent left femoral pulse in patient 2 (10- month-old child) immediately after the procedure (Fig 3). This was managed with a 3-day course of intravenous heparin with restora- tion of a normal pulse.

I DISCUSSION

Hypertension affects approximately 80% of patients with ESRD and approximately 50% of renal transplant recipients remain hypertensive (7). The most common causes of post-transplant hypertension are chronic rejection and cyclo- sporine-induced hypertension. Re- tained native kidneys are a less common cause of persistent, difficult-to-control hypertension via the renin-angiotensin system (8). Hy-

L 1 #

a. b. Figure 3. Patient 2. (a) The postablation aortogram demonstrates occlusion of the renal arteries with bilateral renal parenchymal staining. Note the bilateral common iliac artery vasospasm with minimal flow around the 4-F sheath. (b) The subtracted image better demonstrates the vasospasm.

pertension is an important risk factor for cardiovascular and cere- brovascular disease-the leading causes of death for both dialysis and renal transplant patients. Hypertension also diminishes the survival of the transplanted kidney.

Historically, surgical nephrectomy was a routine procedure per-

formed prior to renal transplantation. This strategy has been dis- carded primarily because of the high morbidity (40%-87%) and mortality (3%-12'%) (9,101. Preser- vation of the native kidneys may also aid in maintenance of fluid balance and provide some vitamin D synthesis and erythropoietin

532 Journal of Vascular and Interventional Radiology

July-August 1997

production. Nephrectomy is indicated in pediatric patients with ESRD and uncontrolled hypertension andlor nephrotic syndrome. Several authors have recently pro- posed that criteria for nephrectomy in patients with ESRD once again be expanded (1,ll-13). The authors acknowledge the fact that dialysis patients who are anephric are more sensitive to volume and electrolyte disturbances and must be fluid restricted. However, improved blood pressure control after nephrectomy may improve morbidity and mortality rates in these patients.

There are a number of studies reporting the low morbidity and mortality of percutaneous renal ablation with absolute alcohol in the setting of ESRD (1-4,14,15). In our patient population, including patients who were ventilator dependent with congestive heart failure and uncontrolled hypertension, surgical intervention would have been extremely hazardous. Such patients are poor surgical candi- dates for standard nephrectomy (9,10), and newer surgical techniques, such as laparoscopic nephrectomy (16-18), remain techni- cally difficult. Although the propo- nents of these newer surgical techniques espouse a lower morbidity and mortality than standard nephrectomy, there is only a single report of mortality related to alcohol ablation of the kidneys (19). This death remains unexplained, but several authors have theorized that alcohol refluxed into the adrenal arteries, despite the use of a balloon occlusion catheter.

In our series of 11 patients with ESRD, transarterial alcohol ablation proved to be effective in con- trolling hypertension and halting nephrotic syndrome. There was no mortality and the morbidity rate was 9%, substantially lower than that in standard surgical series (9,101.

Concentrated ethanol is directly cytotoxic as well as thrombogenic but is rendered harmless by dilu- tion once it traverses the renal vasculature and enters the vena cava (14). Nontarget embolization remains a concern; therefore, a

meticulous search for adrenal, I gonadal, and phrenic branches of the renal arteries is always under- taken ~ r i o r to embolization. There are reports of colonic infarction due to reflux of alcohol into the aorta and streaming into the inferior

L,

mesenteric artery during embolization of renal cell carcinomas (20,21). In these cases, end-hole catheters were used and boluses of 18-25 mL of absolute alcohol were injected. To prevent these complications, we recommend use of a balloon catheter advanced distal to nontarget vessels and slow, fluoroscopically monitored manual injection of alcohol opacified with metrizamide.

In our population, only one patient had a functional renal transplant at the time of renal ablation. Angioplasty of an iliac arteryltransplant renal artery anas- tomotic stenosis was performed at the same setting. Of interest in our series is the fact that the youngest patient (10 months) to undergo renal ablation is the only patient whose hypertension has resolved. We speculate that early intervention may improve the chances of rendering the patient normotensive by limiting the duration of systemic hypertension. Prolonged hypertension may cause an irreversible increase in peripheral vascular resistance resulting from arterial structural adaptation (14).

Renal ablation was very difficult to perform on the 10-month-old child because of the size of the arteries embolized, as well as the degree of vasospasm. Another limi- tation of the procedure was incom- plete embolization in patient 3, which resulted in recurrent hypertension requiring repeated ablation. Despite these limitations and based on our experience plus review of the literature, we believe that transcatheter renal ablation with absolute alcohol should be considered a viable alternative to surgical nephrectomy in patients with ESRD and uncontrolled hypertension or nephrotic syndrome.

Acknowledgment: The authors thank Donna McCain for help in prepa- ration of the manuscript.

References 1. Thompson JF, Wood RFM, Taylor

HM, et al. Control of hypertension after renal transplantation by em- bolisation of host kidneys. Lancet 1984; 2:424-427.

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3. Millard FC, Hemingway AP, Cumber- land DC, Brown CB. Renal embolization for ablation of function in renal failure and hypertension. Postgraduate Med J 1989; 65:72%734.

4. Borge MA, Jaques PF, Mauro MA, Morris CR. Percutaneous renal ablation in children with end-stage renal disease. JVIR 1992; 3:467-474.

5. Tupper TB, Cronan J J , Wald LM, Dorfman GS. Renal abscess: a complication of ethanol ablation. Radiology 1986; 161:35-36.

6. Simon N, Franklin SS, Bleifer KH, Maxwell MH. Clinical characteris- tics of renovascular hypertension. JAMA 1972; 220:1209-1218.

7. Curtis J J . Hypertension and kidney transplantation. Am J Kidney Dis 1986; 7:181-196.

8. Luke RG. Pathology and treatment of post transplant hypertension. J Am Soc Nephrol 1991; 2: 537-544.

9. Matas AJ, Simmons RL, Buselmeier TJ, Najarian JS, Kjellstrand CM. Lethal complications of bilateral nephrectomy and splenectomy in hernodialyzed patients. AJS 1975; 129:616-620.

10. Yarimizu SN, Susan LP, Straffon RA, Stewart BH, Magnusson MO, Nakamoto SS. Morbidity and mortality in prestransplant bilateral nephrectomy: analysis of 305 cases. Urology 1978; 12:55-58.

11. Curtis J J , Luke RG, Whelchel JD, Diethelm AG, Jones P. Benefits of removal of native kidneys in hypertension after renal transplant. Lancet 1985; 2:739-742.

12. Darby CR, Cranston D, Raine AEG, Morris P J Bilateral nephrectomy before transplantation: indications, surgical approach, morbidity and mortality. Br J Surg 1991; 78:305-307.

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percent ethyl alcohol. J Urol 1982; 127:873-875.

15. Klimberg IW, Locke DR, Hawkins IF, Drylie DM. Absolute ethanol renal angioinfarction for control of hypertension. Urology 1989; 33: 153-158.

16. Gill IS, Kavoussi LR, Clayman RV, et al. Complications of laparoscopic nephrectomy in 185 patients: a multi-institutional review. J Urol 1995; 154:479-483.

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18. Novick AC. Posterior surgical approach to the kidney and ureter. J Urol 1980; 124:192-195.

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20. Cox GG, Lee KR, Price HI, Gunter K, Nobel M, Mebust WK. Colonic infarction following ethanol embolization of renal cell carcinoma. Radi- ology 1982; 145343-345.

21. Teetstra HJ, Winter WA, Frensdorf EL. Ethanol embolization of a renal tumor complicated by colonic infarction. Diag Imag Clin Med 1984; 53:250-254.

percutaneous transcatheter renal ablation with absolute ethanol for uncontrolled hypertension or...

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