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Renal Artery Stenosis: The Case for Conservative Management
Mayo Clinic Proceedings
May 2000 Volume 7S NumberS
Renal Artery Stenosis: The Case for Conservative Management
A
therosclerotic renal vascular disease is a well-recognized cause of hypertension and renal failure, particularly in the elderly and in populations with diffuse vascular disease. Ischemic renal disease, defined as a clinically important reduction in glomerular filtration rate in patients with hemodynamically important obstruction to renal blood flow, has been reported to account for 5% to 15% of patients requiring renal replacement therapy. 1,2 In 1992, we initially characterized the prevalence of renal vascular disease in a group of patients referred for diagnostic cardiac catheterization at our institution.' A total of 1235 patients were enrolled in the study and underwent aortography at the time of diagnostic cardiac catheterization to assess for renal vascular disease. Renal vascular disease was identified in a full 30%. Stenoses less than 50% were noted in 15%, and severe renal vascular disease (>50% stenosis) was noted in another 15% (188/1235). The extent of coronary disease, peripheral vascular disease, and congestive heart failure predicted renal vascular disease. Surprisingly, the presence of hypertension was not predictive of renal vascular disease, occurring in fewer than half of patients. Thus, renal artery stenosis (RAS) was often clinically silent, and the exact prevalence and natural history remained largely unknown. Our ability to intervene in this disease process has dramatically improved over the last several years, coinciding with technical improvements in surgical and endovascular approaches. Previously, subjecting this patient population with coronary artery and cerebral vascular disease to extensive abdominal aortic surgery was fraught with complications. Novick and colleagues' first stressed the additional morbidity of entering the aorta and reported improved outcomes with hepatorenal or splenic-renal bypass. Unfortunately, angioplasty of these lesions has been met with limited success due to the ostial nature of these lesions and the high rate of restenosis. More recently, endovascular
stent placement has been shown to have a superior rate of technical success along with a low rate of complications. Recently, van de Ven et al' reported the results of a randomized trial comparing percutaneous transluminal angioplasty (PTA) with stent deployment (PTAS) to PTA alone. Primary success (88% vs 57%) and 6-month patency (75% vs 29%) was higher for PTAS compared with PTA alone. Blum et al" described 74 patients with renal artery stents and a mean follow-up of 27 months. The procedure was technically successful in all with minor complications occurring in few and major complications in none. Frequency of restenosis was low at 10%. Dorros et aF reported similar technical success with mean stenosis decreasing from 81% to 4% and long-term clinical patency with stent placement. Thus, technical advancements have decreased the risks of intervention in patients with RAS, but on which patients to intervene and the expected clinical benefits remain to be determined. In this issue of Proceedings, Chabova et al" describe their experience with 68 patients with high-grade RAS (>70%) who were treated medically without vascular intervention. Their patient population was older and the stenosis was of higher grade than described previously. Patients were identified between 1989 and 1993 with an average follow-up of more than 3 years. Almost all patients (66/68) had known disease in other vascular beds, and a large percentage (31%) had disease affecting both kidneys or obstruction to a single functioning kidney. End points were need for revascularization, nephrectomy, dialysis, or death. See also page 437. Over the course of follow-up there was some decline in renal function with the creatinine level rising from 1.4 mg/ dl. to 2.0 mg/dl., and although there was no change in blood pressure, slightly more medications were required. Eighty-five percent had stable renal function through the 3 years offollow-up. Remarkably, we think, even in patients with bilateral RAS, the majority (81%) had no deterioration in renal function. The risk of progressive renal failure was only 12.8% in the group with unilateral disease and
Address reprint requests and correspondence to Steve J. Schwab, MD, Division of Nephrology, Department of Medicine, Duke University Medical Center, Box 3014, Durham, NC 27710.
Mayo Clin Proc. 2000;75:435-436
435
© 2000 Mayo Foundation for Medical Education and Research
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Mayo Coo Proc, May 2000, Vol 75
19% in the group with bilateral disease. Although a total of 6 (8.8%) of 68 reached end-stage renal disease (ESRD), other causes of renal failure were identified in the majority. In total, only 2 of 68 advanced to ESRD from progressive renal artery occlusion. Prior studies evaluating the natural history have quoted between 29% and 71% risk for progression with between 8% and 15% developing total occlusion.l-' All of these studies have been done in small numbers of selected patients making generalizability to the patient population difficult. Recently, Caps et a19,10 reported on duplex ultrasonographic follow-up in 295 kidneys of 170 patients followed up for a mean of 33 months. Progression based on duplex determination was 35% at 3 years and 51% at 5 years. Nine renal artery occlusions (3%) occurred over the course of the study. Occlusion was not a common course and occurred most frequently in patients with high-grade stenosis, severe hypertension, and diabetes mellitus. Additionally, all occlusions occurred in patients with greater than60% stenosis on the study prior to occlusion. At our institution, disease progression was assessed in 1189 patients undergoing follow-up cardiac catheterization with aortography." Mean duration between angiograms was 2.6 years. Eleven percent (133/1189) had severe progression. Not surprisingly these vessels tended to progress in a time-dependent fashion with fully 25% of patients demonstrating progressive disease by the 5-year mark. Although radiographic progression was demonstrable, there was little clinical change. Mortality over the course of follow-up was high in the patient population described by Chabova et a1. Nineteen (27.9%) of 68 died, with the major cause being cardiovascular mortality. Conlon et al 12 reported on mortality in our original cohort with renal vascular disease discovered at catheterization. Four-year mortality was 35% in patients with RAS compared with 14% in patients without disease. Patients with RAS were more likely to have severe coronary artery disease and a depressed ejection fraction, and RAS was a strong independent predictor of mortality. The major cause of death in patients with or without RAS was cardiovascular disease. Similarly, Dorros et al? described 163 patients with stent placement for poorly controlled hypertension or progressive renal failure with follow-up of 4 years. Cumulative mortality was 26% at 3 years. Those with poor initial glomerular filtration rate had the highest 3-year mortality-48%. The combination of impaired renal function and renal vascular disease was a strong predictor of mortality, despite intervention. In the present study, the 3-year mortality of patients without intervention was similar to that of previously reported groups undergoing vascular stenting. This suggests, as Conlon et al 12 noted, that the presence of RAS is a predictor of severity of disease in other vascular beds. Correction of the RAS itself mayor may not
Editorial
436
affect mortality. Therefore, although RAS may progress, death often occurs from coronary or cerebral vascular disease before decline in renal function has any effect. In conclusion, the study by Chabova et al offers longterm follow-up in a large group of patients observed without vascular intervention. The level of disease in this population was relatively severe and the population was older than that in previous reports. The renal outcome was surprisingly good. Only 2 of 68 patients progressed to ESRD from renal ischemia, and 1 of those was prospectively identified but refused intervention. The overall mortality in this group of patients is high, and mortality is largely attributable to cardiovascular death. Although vascular and endovascular intervention is low risk, these data argue that the benefits are likewise modest. The authors argue compellingly that careful follow-up, with early intervention in patients with progression, may be the best course of action. Thus, cautious selection of patients for early intervention along with meticulous follow-up, saving intervention for those with demonstrable progression, may offer the best course at present. David W. Butterly, MD Steve 1. Schwab, MD Duke University School of Medicine Durham,NC REFERENCES 1. Jacobson HR. Ischemic renal disease: an overlooked clinical entity? Kidney Int. 1988;34:729-743. 2. Rimmer JM, Gennari FJ. Atherosclerotic renovascular disease and progressive renal failure. Ann InternMed. 1993;1l8:712-719. 3. Harding MB, Smith LR, Himmelstein SI, et al. Renal artery stenosis: prevalence and associated risk factors in patients undergoing routine cardiac catheterization. J Am Soc Nephrol. 1992;2:1608-1616. 4. Novick AC, Straffon RA, Stewart BH, Gifford RW, Vidt D. Diminished operative morbidity and mortality in renal revascularization. JAMA. 1981;246:749-753. 5. van de Ven PJ, Kaatee R, Beutler Ll, et al. Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial. Lancet. 1999;353:282-286. 6. Blum D, Krumme B, Flugel P, et al. Treatment of ostial renal-artery stenosis with vascular endoprostheses after unsuccessful balloon angioplasty. N Engl J Med. 1997;336:459-465. 7. Dorros G, JaffM, Mathiak L, Lowe A, Murphy K, He T. Four-year follow-up ofPalmaz-Schatz stent revascularization as treatment for atherosclerotic renal artery stenosis. Circulation. 1998;98:642-647. 8. Chabova V, Schirger A, Stanson AW, McKusick MA, Textor SC. Outcomes of atherosclerotic renal artery stenosis managed without revascularization. Mayo Clin Proc. 2000;75:437-444. 9. Caps MT, Zierler RE, Polissar NL, et al. Risk of atrophy in kidneys with atherosclerotic renal artery stenosis. Kidney Int. 1998;53:735742. 10. Caps MT, Perissinotto C, Zierler RE, et al. Prospective study of atherosclerotic disease progression in the renal artery. Circulation. 1998;98:2866-2872. 11. Crowley Ll, Santos RM, Peter RH, et al. Progression of renal artery stenosis in patients undergoing cardiac catheterization. Am Heart J. 1998;136:913-918. 12. Conlon PJ, Athirakul K, Kovalik E, et al. Survival in renal vascular disease. JAm Soc Nephrol. 1998;9:252-256.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
May 2000 Volume 7S NumberS
Renal Artery Stenosis: The Case for Conservative Management
A
therosclerotic renal vascular disease is a well-recognized cause of hypertension and renal failure, particularly in the elderly and in populations with diffuse vascular disease. Ischemic renal disease, defined as a clinically important reduction in glomerular filtration rate in patients with hemodynamically important obstruction to renal blood flow, has been reported to account for 5% to 15% of patients requiring renal replacement therapy. 1,2 In 1992, we initially characterized the prevalence of renal vascular disease in a group of patients referred for diagnostic cardiac catheterization at our institution.' A total of 1235 patients were enrolled in the study and underwent aortography at the time of diagnostic cardiac catheterization to assess for renal vascular disease. Renal vascular disease was identified in a full 30%. Stenoses less than 50% were noted in 15%, and severe renal vascular disease (>50% stenosis) was noted in another 15% (188/1235). The extent of coronary disease, peripheral vascular disease, and congestive heart failure predicted renal vascular disease. Surprisingly, the presence of hypertension was not predictive of renal vascular disease, occurring in fewer than half of patients. Thus, renal artery stenosis (RAS) was often clinically silent, and the exact prevalence and natural history remained largely unknown. Our ability to intervene in this disease process has dramatically improved over the last several years, coinciding with technical improvements in surgical and endovascular approaches. Previously, subjecting this patient population with coronary artery and cerebral vascular disease to extensive abdominal aortic surgery was fraught with complications. Novick and colleagues' first stressed the additional morbidity of entering the aorta and reported improved outcomes with hepatorenal or splenic-renal bypass. Unfortunately, angioplasty of these lesions has been met with limited success due to the ostial nature of these lesions and the high rate of restenosis. More recently, endovascular
stent placement has been shown to have a superior rate of technical success along with a low rate of complications. Recently, van de Ven et al' reported the results of a randomized trial comparing percutaneous transluminal angioplasty (PTA) with stent deployment (PTAS) to PTA alone. Primary success (88% vs 57%) and 6-month patency (75% vs 29%) was higher for PTAS compared with PTA alone. Blum et al" described 74 patients with renal artery stents and a mean follow-up of 27 months. The procedure was technically successful in all with minor complications occurring in few and major complications in none. Frequency of restenosis was low at 10%. Dorros et aF reported similar technical success with mean stenosis decreasing from 81% to 4% and long-term clinical patency with stent placement. Thus, technical advancements have decreased the risks of intervention in patients with RAS, but on which patients to intervene and the expected clinical benefits remain to be determined. In this issue of Proceedings, Chabova et al" describe their experience with 68 patients with high-grade RAS (>70%) who were treated medically without vascular intervention. Their patient population was older and the stenosis was of higher grade than described previously. Patients were identified between 1989 and 1993 with an average follow-up of more than 3 years. Almost all patients (66/68) had known disease in other vascular beds, and a large percentage (31%) had disease affecting both kidneys or obstruction to a single functioning kidney. End points were need for revascularization, nephrectomy, dialysis, or death. See also page 437. Over the course of follow-up there was some decline in renal function with the creatinine level rising from 1.4 mg/ dl. to 2.0 mg/dl., and although there was no change in blood pressure, slightly more medications were required. Eighty-five percent had stable renal function through the 3 years offollow-up. Remarkably, we think, even in patients with bilateral RAS, the majority (81%) had no deterioration in renal function. The risk of progressive renal failure was only 12.8% in the group with unilateral disease and
Address reprint requests and correspondence to Steve J. Schwab, MD, Division of Nephrology, Department of Medicine, Duke University Medical Center, Box 3014, Durham, NC 27710.
Mayo Clin Proc. 2000;75:435-436
435
© 2000 Mayo Foundation for Medical Education and Research
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Mayo Coo Proc, May 2000, Vol 75
19% in the group with bilateral disease. Although a total of 6 (8.8%) of 68 reached end-stage renal disease (ESRD), other causes of renal failure were identified in the majority. In total, only 2 of 68 advanced to ESRD from progressive renal artery occlusion. Prior studies evaluating the natural history have quoted between 29% and 71% risk for progression with between 8% and 15% developing total occlusion.l-' All of these studies have been done in small numbers of selected patients making generalizability to the patient population difficult. Recently, Caps et a19,10 reported on duplex ultrasonographic follow-up in 295 kidneys of 170 patients followed up for a mean of 33 months. Progression based on duplex determination was 35% at 3 years and 51% at 5 years. Nine renal artery occlusions (3%) occurred over the course of the study. Occlusion was not a common course and occurred most frequently in patients with high-grade stenosis, severe hypertension, and diabetes mellitus. Additionally, all occlusions occurred in patients with greater than60% stenosis on the study prior to occlusion. At our institution, disease progression was assessed in 1189 patients undergoing follow-up cardiac catheterization with aortography." Mean duration between angiograms was 2.6 years. Eleven percent (133/1189) had severe progression. Not surprisingly these vessels tended to progress in a time-dependent fashion with fully 25% of patients demonstrating progressive disease by the 5-year mark. Although radiographic progression was demonstrable, there was little clinical change. Mortality over the course of follow-up was high in the patient population described by Chabova et a1. Nineteen (27.9%) of 68 died, with the major cause being cardiovascular mortality. Conlon et al 12 reported on mortality in our original cohort with renal vascular disease discovered at catheterization. Four-year mortality was 35% in patients with RAS compared with 14% in patients without disease. Patients with RAS were more likely to have severe coronary artery disease and a depressed ejection fraction, and RAS was a strong independent predictor of mortality. The major cause of death in patients with or without RAS was cardiovascular disease. Similarly, Dorros et al? described 163 patients with stent placement for poorly controlled hypertension or progressive renal failure with follow-up of 4 years. Cumulative mortality was 26% at 3 years. Those with poor initial glomerular filtration rate had the highest 3-year mortality-48%. The combination of impaired renal function and renal vascular disease was a strong predictor of mortality, despite intervention. In the present study, the 3-year mortality of patients without intervention was similar to that of previously reported groups undergoing vascular stenting. This suggests, as Conlon et al 12 noted, that the presence of RAS is a predictor of severity of disease in other vascular beds. Correction of the RAS itself mayor may not
Editorial
436
affect mortality. Therefore, although RAS may progress, death often occurs from coronary or cerebral vascular disease before decline in renal function has any effect. In conclusion, the study by Chabova et al offers longterm follow-up in a large group of patients observed without vascular intervention. The level of disease in this population was relatively severe and the population was older than that in previous reports. The renal outcome was surprisingly good. Only 2 of 68 patients progressed to ESRD from renal ischemia, and 1 of those was prospectively identified but refused intervention. The overall mortality in this group of patients is high, and mortality is largely attributable to cardiovascular death. Although vascular and endovascular intervention is low risk, these data argue that the benefits are likewise modest. The authors argue compellingly that careful follow-up, with early intervention in patients with progression, may be the best course of action. Thus, cautious selection of patients for early intervention along with meticulous follow-up, saving intervention for those with demonstrable progression, may offer the best course at present. David W. Butterly, MD Steve 1. Schwab, MD Duke University School of Medicine Durham,NC REFERENCES 1. Jacobson HR. Ischemic renal disease: an overlooked clinical entity? Kidney Int. 1988;34:729-743. 2. Rimmer JM, Gennari FJ. Atherosclerotic renovascular disease and progressive renal failure. Ann InternMed. 1993;1l8:712-719. 3. Harding MB, Smith LR, Himmelstein SI, et al. Renal artery stenosis: prevalence and associated risk factors in patients undergoing routine cardiac catheterization. J Am Soc Nephrol. 1992;2:1608-1616. 4. Novick AC, Straffon RA, Stewart BH, Gifford RW, Vidt D. Diminished operative morbidity and mortality in renal revascularization. JAMA. 1981;246:749-753. 5. van de Ven PJ, Kaatee R, Beutler Ll, et al. Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial. Lancet. 1999;353:282-286. 6. Blum D, Krumme B, Flugel P, et al. Treatment of ostial renal-artery stenosis with vascular endoprostheses after unsuccessful balloon angioplasty. N Engl J Med. 1997;336:459-465. 7. Dorros G, JaffM, Mathiak L, Lowe A, Murphy K, He T. Four-year follow-up ofPalmaz-Schatz stent revascularization as treatment for atherosclerotic renal artery stenosis. Circulation. 1998;98:642-647. 8. Chabova V, Schirger A, Stanson AW, McKusick MA, Textor SC. Outcomes of atherosclerotic renal artery stenosis managed without revascularization. Mayo Clin Proc. 2000;75:437-444. 9. Caps MT, Zierler RE, Polissar NL, et al. Risk of atrophy in kidneys with atherosclerotic renal artery stenosis. Kidney Int. 1998;53:735742. 10. Caps MT, Perissinotto C, Zierler RE, et al. Prospective study of atherosclerotic disease progression in the renal artery. Circulation. 1998;98:2866-2872. 11. Crowley Ll, Santos RM, Peter RH, et al. Progression of renal artery stenosis in patients undergoing cardiac catheterization. Am Heart J. 1998;136:913-918. 12. Conlon PJ, Athirakul K, Kovalik E, et al. Survival in renal vascular disease. JAm Soc Nephrol. 1998;9:252-256.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.