What are the Clinical Success Rates of Renal Intervention?

with good technical results in patients without a hypercoagulable disorder. Studies of Coumadin in the 1990's did not show improved occlusion or restenosis rates relative to ASA, but had more complications. CONCLUSION Current stents and techniques for atherosclerotic renal artery lesions seem to be yielding an angiographic restenosis rate of approximately 20% at close to 1 year, with drop-off after 1 year that is not yet well defined. The association of these restenotic lesions with clinical symptoms is variable, and detection of restenosis is therefore often difficult, and made more difficult by lack of a powerful non-invasive imaging modality. The emphasis of clinical reports has shifted somewhat from patency data to the clinical relevance and complications of the proceudure in general, which has come under fire from non-interventional specialties. Now that stents and implant techniques have been well refined, further reduction of restenosis will most likely require a significant paradigm change. The most imminent possibility seems to be drug-eluting technology, which has been successful in the coronary vessels, but is as yet poorly available for use in renal arteries. Small stent-grafts could potentially be developed for renal vessels, but are currently not well suited for general use. Brachytherapy has been sporadically reported in a few cases, for initial stenting as well as treatment of in-stent restenosis, and at this time may be clinically useful in problematic restenosis cases (9).

References 1. Van de Ven, et al. Arterial stenting a balloon angio-

plasty in ostial atherosclerotic renovascular disease: a randomized trial. Lancet 1999; 353:282-286. 2. Sivamurthy N, et al. Divergent outcomes after percutaneous therapy for symptomatic renal artery stenosis. ] Vasc Surg 2004; 39:565-74. 3. Bakker J, et al. Duplex ultrasonography in assessing restenosis of renal artery stents. CVIR 1999; 22:475480. 4. Mallouhi A, et al. Volume-Remdered multidetector CTAngiography: Noninvasive follow-up of patients treated with renal artery stents. AJR 2003; 180:233239. 5. Shammas NW, et al. Clinical and angiographic predictors of restenosis following renal artery stenting. J Invasive Cardiol. 2004 Jan; 16(1): 13. 6. Gill-Leertouwer, et al. Shrinkage of the distal renal artery 1 year after stent placement as evidenced with serial intravascular ultrasound. Br ] Radiol. 2002 Nov; 75(899):879-83. 7. Lederman R], et al. Primary renal artery stenting: characteristics and outcomes after 363 procedures. Am Heart]. 2001 Aug; 142(2): 314-23 8. Kennedy D], et al. Renal insufficiency as a predictor of

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adverse events and mortality after renal artery stent placement. Am] Kidney Dis. 2003 Nov; 42(5): 926-35. 9. Bakker ], et al. The Erasme study: a multicenter study on the safety and technical results of the Palmaz stent used for the treatment of atherosclerotic ostial renal artery stenosis. Cardiovasc Intervent Radiol. 1999 Nov-Dec; 22(6): 468-74. 10. Bakker], et al. Duplex ultrasonography in assessing restenosis of renal artery stents. Cardiovasc Intervent Radiol. 1999 Nov-Dec; 22(6): 475-80. 11. Bax 1. Repeated intervention for in-stent restenosis of the renal arteries.]VIR 2002; 13:1219-1224 12. Rees, CR. Stents for atherosclerotic renovascular disease. ]VIR 1999; 10:689-705. 13. Cioni R, et al. Renal artery stenting in patients with a solitary functioning kidney. Cardiovasc Intervent Radiol. 2001 Nov-Dec; 24(6): 372-7. 14. Sivamurthy N, et al. Divergent outcomes after percutaneous therapy for symptomatic renal artery stenosis. ] Vasc Surg. 2004 Mar; 39(3): 565-74. 15. Zeller T, et al. Gold coating and restenosis after primary stenting of ostial renal artery stenosis. Catheter Cardiovasc Interv. 2003 Sep; 60(1); 1-6; discussion. 16. Ramos F, Renal function and outcome of PTRA and stenting for atherosclerotic renal artery stenosis. Kidney Int. 2003 Jan; 630): 276-82. 17. Spratt ]C, et al. A case of renal artery brachytherapy for in-stent restenosis: four-year follow-up. ] Invasive Cardiol 2004 16:287-8. 18. Symonides B, et al. Plasma fibrinogen as a risk factor for restenosis after percutaneous transluminal renal angioplasty in patients with atherosclerotic renal artery stenosis. ] Cardiovasc Risk. 1999 Aug;6(4): 269-72 19. Stoeteknuel-Friedli S, et al. Endovascular brachytherapy for prevention of recurrent renal in-stent restenosis. ] Endovasc Ther. 2002 ]un; 9(3): 350-3

8:35 a.m. What are the Clinical Success Rates of Renal Intervention? Julio C. Palmaz, MD

The University of Texas Health Science Center San Antonio, TX Incidence of renovascular disease (RVD) The incidence of end-stage renal disease (ESRD) from RVD is increasing at an average rate of 12.4% per year. This annual increment for RVD is larger than any other cause of ESRD including diabetes mellitus, 0, 2) RVD and particularly atherosclerotic renal artery stenosis (RAS) are included in the category of Hypertension/large vessel disease in the USRDS database.(2) As in previous

reports, the USRDS 2000 report continues to disclose the category of Hypertension/large vessel disease as the second largest cause of ESRD, following diabetes. Despite the magnitude of this category there is no report on the fractional incidence of RAS, which is suspected to be the largest component.(3) Since 425,000 patients are in the USRDS database, in government-supported dialysis or transplant programs, the social and economic impact of RAS is deemed to be large. Epidemiological factors related to RAS include age older than 65, female gender, white race and elevated systolic blood pressure.(4) Clinical suspicion is established on: 1) hypertension before age 30 or after 55 2) malignant or accelerated hypertension 3) uncontrolled hypertension, previously well controlled 4) advanced atherosclerosis 5) epigastric bruit 6) azotemia caused by ACE inhibitor 7) unexplained azotemia 8) unilateral small kidney 9) flash pulmonary edema. (5) Screening by flush aortogram is justified in any patient older than 55 who undergoes diagnostic vascular catheterization for coronary, cerebrovascular or peripheral vascular disease. MRA and duplex US and Captopril renography are adequate screening tools. Besides the usual laboratory screening for renal function, risk factors for RAS and long-term preservation of therapeutic benefit can be further established by high denSity lipoprotein (HDL) cholesterol (4), high serum fibrinogen concentration (6), and the DD phenotype for the angiotensin converting enzyme gene.(7) These parameters are also markers for advanced atherosclerotic disease, of which RAS and ESRD are part of the spectrum. Indications for percutaneous revascularization of RAS

The effect of revascularization on high blood pressure and renal function appear to be dependent on baseline values. Interestingly, the level of severity of systolic BP correlates positively with the degree of improvement 6 months after treatment.(8) In other words, the more severe the systolic hypertension, the better are the expected results. Conversely, high degree of renal functional loss does not respond favorably to revascularization.(9) However, post-revascularization improvement correlates with rapid onset of renal functional deterioration. This is observed in patients with negarive slope values of reciprocal creatinine concentration inversely correlating with post-treatment slope changes. (1 0) Therefore, patients who had sustained renal function loss or slowly deteriorating renal function derive the least benefit from revascularization. Conversely, those who have been loosing renal function over a relatively short period are likely to improve from revascularization. The possibility of atheroembolization caused by aortic or selective catheterization of the renal arteries has been a deterrent to Widespread application of endovascular teChniques. Microvessel embolization of cholesterol crystals produces severe, irreversible renal functional

loss in 1-2% of cases. However, partial undetectable functional loss has not been ruled out in a larger percentage of patients undergoing renal revascularization. Recent evidence indicates that this is not the case, and that glomerular filtration rate consistently improves after catheter-based revascularization techniques.(11) The use of embolic protection techniques to increase the margin of safety against embolization, is being increasingly adopted. However, lack of proof of benefit and appropriate equipment for the renal arteries makes this approach currently debatable. Results of percutaneous treatment of RAS A formal multicenter, randomized study comparing sents and PTRA was never performed. However, review of the current literature indicates an average restenosis rate of 17% for stents and 26% for PTRA.(12) Stenting with bare metal stents has been steadily improving. In 1998, Rees et al reported a restenosis rate of 37%.(13) In 2001 the ASPIRE II trial showed a restenosis rate of 17%.(14) In 2003 the GREAT trial had a restenosis rate of 15%.(15) The GREAT trial compared bare metal against drug eluting stents (DES) in a randomized fashion. The DES had a restenosis rate of 7.5% at 6 months. The difference approached significance but a larger study is necessary to further demonstrate the benefit.

References 1. Fatica RA, Port FK, Young EW. Incidence trends and mortality in end-stage renal disease attributed to renovascular disease in the United States. American Journal of Kidney Diseases [Onlinel. 2001; 37:118490. 2. USRDS. United States Renal Data System. USRDS 1997 Annual Data Report. Bethesda, MD. Uriited States Renal Data System 1997. 3. Mailloux LU, Napolitano B, Bellucci AG, Vernace M, Wilkes BM, Mossey RT. Renal vascular disease causing end-stage renal disease, incidence, clinical correlates, and outcomes: a 20-year clinical experience. American Journal of Kidney Diseases. 1994; 24:622-9. 4. Hansen KJ, Edwards MS, Craven TE, et al. Prevalence of renovascular disease in the elderly: a population-based study. Journal of Vascular Surgery. 2002; 36:443-51. 5. Vashist A, Heller EN, Brown EJ, Jr., Alhaddad lAo Renal artery stenosis: a cardiovascular perspective. American Heart Journal. 2002; 143:559-64. 6. Hicks RC, Ellis M, Mir-Hasseine R, et al. The influence of fibrinogen concentration on the development of vein graft stenoses. European Journal of Vascular & Endovascular Surgery 1995; 9:415-20. 7. Losito A, Parente B, Cao PG, Jeffery S, Afzal AR. ACE gene polymorphism and survival in atherosclerotic

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renovascular disease. American Journal of Kidney Diseases [Online]. 2000; 35:211-5. 8. Burket MW, Cooper CJ, Kennedy DJ, et al. Renal artery angioplasty andstent placement: predictors of a favorable outcome. American Heart Journal. 2000; 139:64-71. 9. Dorros G, Jaff M, Mathiak L, He T, Multicenter Registry P. Multicenter Palmaz stent renal artery stenosis revascularization registry report: four-year follow-up of 1,058 successful patients. Catheterization & Cardiovascular Interventions. 2002; 55: 182-8. 10. Muray S, Martin M, Amoedo ML, et al. Rapid decline in renal function reflects reversibility and predicts the outcome after angioplasty in renal artery stenosis. American Journal of Kidney Diseases [Online]. 2002; 39:60-6. 11. La Batide-Alanore A, Azizi M, Froissart M, Raynaud A, Plouin PF. Split renal function outcome after renal angioplasty in patients with unilateral renal artery stenosis. Journal of the American Society of Nephrology. 2001; 12:1235-41. 12. Leertouwer TC, Gussenhoven EJ, Bosch JL, et al. Stent placement for renal arterial stenosis: where do we stand? A meta-analysis. Radiology 2000; 216:7885. 13. Rees CR. Stents for atherosclerotic renovascular disease.[erratum appears in J Vasc Interv Radiol 1999 Sep;10(8);1118]. [Review] [86 refs]. Journal of Vascular & Interventional Radiology. 1999 Jun;1O(6);6897051999. 14. Raabe R. Use of the Palmaz balloon-expandable stent in the treatment of renal artery stenosis. ASPIRE II trial, SIR, Salt Lake City, 2003. 15. Zaehringer M. GREAT. Renal stenting comparing sirolimus-eluting Genesis stent vs bare Genesis stents, Euro PCR, Paris, France, 2004. 8:45 a.m. How Does Renal Intervention Compare to Medical Management Alone? Timothy P. Murphy, MD Rhode Island Hospital Providence, Rl If one were to examine the increasing annual volume of renal artery interventions performed in the U.S. they would likely conclude that renal artery interventions must provide tremendous benefit (1). Annual volumes of renal artery angioplasty and stent placement increased 2.4 fold in 2000 compared with 1996 (1). Ironically, there is no randomized controlled clinical trial data that shows clinical benefit for renal artery angioplasty or stent placement. There are only 3 randomized controlled clinical trials of renal artery angioplasty (2-4), and none for stent placement.

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The randomized clinical trials compared renal artery angioplasty with medical therapy using blood pressure as a surrogate endpoint (2-4) and overall reported a lack of benefit of renal artery angioplasty to control blood pressure. The largest randomized trial comparing medical treatment and PTRA is the DRASTIC (Dutch Renal Artery Stenosis Intervention Cooperative) Study (2). In this study performed at 26 sites in the Netherlands between 1993 and 1998, 1205 patients with refractory hypertension were referred for evaluation. Of these, 169 patients were found to have at least one renal artery stenosis >50%. One-hundred six went on to randomization, with 56 randomized to PTRA and 50 to medical treatment. The primary endpoints were systolic and diastolic blood pressure analyzed as continuous variables, number and doses of antihypertensive medications, and renal function. At 3 and 12 months, the authors reported "little benefit" of angioplasty over medical therapy for their patients (2). By virtue of the study design medical therapy in the PTRA group was restricted, but refractory patients in the drug-therapy group were allowed to receive balloon angioplasty, and 44% did after 3 months. This heavily biased the 12 month results, in which a substantial number of those in the medical therapy group had received PTRA. Interestingly, secondary analysis of their data reveals that patients in the PTRA group were significantly more likely to have improvement in their blood pressure control (68% v. 38%, P < 0.005), more likely to be cured (7% v. 0%, P = 0.07), and significantly less likely to have either a worsening of their blood pressure control (9% v. 33%, P = 0.002) or renal artery occlusion (0% v. 16%, P = 0.002) during the twelve months of follow-up (2). A smaller randomized study compared 26 patients with medications and 23 with angioplasty (3). Fifteen of the 23 patients in the PTRA group had been managed with a single drug, and therefore they would not be considered resistant to drug therapy according to the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) (5). Less than half had lateralizing captopril scans and only 35% had severe renal artery stenosis (>75%), which raises the question as to whether many of the patients in this study even had renal artery hypertension (3). Although the study was felt to be negative in that blood pressures in both treatment groups were similar at 6 months, 7 (27%) patients in the medication group crossed-over to PTRA during the study, and angioplasty reduced the likelihood of requiring 2 or more antihypertensive medications by 60% (3). Another study of 55 patients randomized to PTRA or medical therapy, blood pressure improvement with PTRA was shown to be limited to those with bilateral renal artery stenosis (4). However, patients were included using angiographic criteria of 50% stenosis (28,61), usually not a threshold of narrowing associated with clinical disease (6,7). This study was small and only 12 patients with unilateral renal artery stenosis received PTRA (4). Of 135 patients eligi-