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- W1991906068 abstract "Occlusion of the renal arteries can threaten the viability of the kidney when severe, in addition to accelerating hypertension and circulatory congestion. Renal artery stenting procedures have evolved from a treatment mainly for renovascular hypertension to a maneuver capable of recovering threatened renal function in patients with ‘ischemic nephropathy’ and improving management of congestive heart failure. Improved catheter design and techniques have reduced, but not eliminated, hazards associated with renovascular stenting. Expanded use of endovascular stent grafts to treat abdominal aortic aneurysms has introduced a new indication for renal artery stenting to protect the renal circulation when grafts cross the origins of the renal arteries. Although controversial, prospective randomized trials to evaluate the added benefit of revascularization to current medical therapy for atherosclerotic renal artery stenosis until now have failed to identify major benefits regarding either renal function or blood pressure control. These studies have been limited by selection bias and have been harshly criticized. While studies of tissue oxygenation using blood-oxygen-level-dependent (BOLD) magnetic resonance establish that kidneys can adapt to reduced blood flow to some degree, more severe occlusive disease leads to cortical hypoxia associated with microvascular rarefaction inflammatory injury, and fibrosis. Current research is directed toward identifying pathways of irreversible kidney injury due to vascular occlusion and to increase the potential for renal repair after restoring renal artery patency. The role of nephrologists likely will focus upon recognizing the limits of renal adaptation to vascular disease and identifying kidneys truly at risk for ischemic injury at a time point when renal revascularization can still be of benefit to recovering kidney function. Occlusion of the renal arteries can threaten the viability of the kidney when severe, in addition to accelerating hypertension and circulatory congestion. Renal artery stenting procedures have evolved from a treatment mainly for renovascular hypertension to a maneuver capable of recovering threatened renal function in patients with ‘ischemic nephropathy’ and improving management of congestive heart failure. Improved catheter design and techniques have reduced, but not eliminated, hazards associated with renovascular stenting. Expanded use of endovascular stent grafts to treat abdominal aortic aneurysms has introduced a new indication for renal artery stenting to protect the renal circulation when grafts cross the origins of the renal arteries. Although controversial, prospective randomized trials to evaluate the added benefit of revascularization to current medical therapy for atherosclerotic renal artery stenosis until now have failed to identify major benefits regarding either renal function or blood pressure control. These studies have been limited by selection bias and have been harshly criticized. While studies of tissue oxygenation using blood-oxygen-level-dependent (BOLD) magnetic resonance establish that kidneys can adapt to reduced blood flow to some degree, more severe occlusive disease leads to cortical hypoxia associated with microvascular rarefaction inflammatory injury, and fibrosis. Current research is directed toward identifying pathways of irreversible kidney injury due to vascular occlusion and to increase the potential for renal repair after restoring renal artery patency. The role of nephrologists likely will focus upon recognizing the limits of renal adaptation to vascular disease and identifying kidneys truly at risk for ischemic injury at a time point when renal revascularization can still be of benefit to recovering kidney function. ‘It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity…’Charles Dickens, A Tale of Two Cities Rarely have competing technical advances in medicine, as in the case of managing renal artery stenosis (RAS) by endovascular stenting or antihypertensive medical therapy, become so successful over precisely the same time interval. On one hand, restoring blood flow to an ischemic kidney beyond vascular occlusion seems to provide an obvious means to restore kidney function and improve blood pressure, sometimes significantly. On the other hand, prospective trials seeking to define the role for renal revascularization up to now have failed to establish a compelling added benefit for endovascular stenting when added to effective medical regimens.1.Steichen O. Amar L. Plouin P.F. Primary stenting for atherosclerotic renal artery stenosis.J Vasc Surg. 2010; 51: 1574-1580Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar,2.Textor S.C. Lerman L. McKusick M. The uncertain value of renal artery interventions: where are we now?.JACC Cardiovasc Interv. 2009; 2: 175-182Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Clinicians caring for patients with renovascular disease understandably find themselves confused by ambiguous clinical observations and disappointing results from prospective randomized trials. Many argue that the trials have been flawed and potentially misleading.3.Mann S.J. Sos T.A. Misleading results of randomized trials: the example of renal artery stenting.J Clin Hypertens. 2010; 12: 1-2Crossref Scopus (10) Google Scholar,4.White C.J. The need for randomized trials to prove the safety and efficacy of parachutes, bulletproof vests, and percutaneous renal intervention.Mayo Clinic Proc. 2011; 86: 603-605Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar Issues of patient selection, statistical quirks, professional bias, and flawed study designs continue to leave the role of stenting a matter of active debate and sometimes obscure basic truths that interfere with optimal patient care. To complicate matters further, newer aortic procedures for the treatment of abdominal aneurysms introduce a new potential source of renal artery occlusion that can threaten kidney viability. The purpose of this review is to place the role of renal revascularization into context as a tool for management of atherosclerotic renal disease threatening renal function and blood pressure control. It has been nearly 80 years since landmark studies of Goldblatt et al.5.Goldblatt H. Lynch J. Hanzal R.E. et al.Studies on experimental hypertension I: the production of persistent elevation of systolic blood pressure by means of renal ischemia.J Exp Med. 1934; 59: 347-379Crossref PubMed Google Scholar and Loesch et al.6.Loesch J. Ein Beitrag zur experimentellen Nephrtis und zum arteriellen Hochdruck III. Die Veranderungen in den Geweben.Zentralblatt Inn Med. 1933; 7: 177-185Google Scholar established that sustained reduction of renal blood flow can raise systemic arterial pressure. Since then, renovascular occlusion has been among the most extensively studied forms of experimental hypertension. Indeed, the premise that signals originating from the kidney could not only affect urine formation and solute excretion but could also modify systemic hemodynamics, endocrine systems, central and peripheral nervous system pathways, vascular structure, cardiac function, and systemic resistance provides the foundation for whole systems of understanding of animal and human physiology.7.Guyton A.C. Dominant role of the kidneys in long-term regulation of arterial pressure and hypertension: the integrated system for pressure control, chap. 19.in: Guyton A.C. Textbook of Medical Physiology. 8 edn. W.B. Saunders Company, Philadelphia1991: 205-220Google Scholar,8.Basso N. Terragno N.A. History about the discovery of the renin-angiotensin system.Hypertension. 2001; 38: 1246-1249Crossref PubMed Google Scholar From a clinical perspective, recognition that reduced renal blood flow sometimes triggers renovascular hypertension and can impair glomerular filtration provides a prototype for ‘secondary hypertension’ that can sometimes be ‘cured’ or ‘improved’ after restoring kidney perfusion by revascularization. It should be emphasized that before surgical revascularization was technically possible in the 1960s, clinicians had few effective treatments to reverse malignant phase hypertension. These sometimes included surgical thoracoabdominal sympathectomy and/or nephrectomy to remove a ‘pressor’ kidney.9.Stanley J.C. Surgical treatment of renovascular hypertension.Am J Surg. 1997; 174: 102-110Abstract Full Text PDF PubMed Scopus (28) Google Scholar Since then, progress regarding imaging of the vascular anatomy, identification of pressor hormones from the kidney, and restoration of blood supply through endovascular methods has been stunning.10.Textor S.C. Lerman L.O. Renovascular hypertension and ischemic nephropathy: state of the art.Am J Hypertens. 2010; 23: 1159-1169Crossref PubMed Scopus (64) Google Scholar The ability to safely reach the vascular bed of major renal arteries and to restore blood flow allows endovascular intervention for many patients who would never be considered for open surgical procedures. Vascular surgical techniques in the 1960s developed sufficiently to allow control and successful operative intervention on the abdominal aorta for acute renal artery occlusion.11.Morris G.C. DeBakey N.E. Cooley D.A. Surgical treatment of renal failure of renovascular origin.JAMA. 1962; 182: 609-612Crossref Google Scholar Partly because of these developments, intravascular contrast agents and vascular imaging became important to establish the diagnosis and anatomy of vascular disease. Early imaging of the abdominal aorta was undertaken through translumbar placement of a needle for contrast injection. Success at developing flexible catheters that could be introduced via a guidewire placed into the femoral artery came later and has been attributed to the successful use of the ‘Seldinger technique.’12.King B.F. Diagnostic imaging evaluation of renovascular hypertension.Abdom Imaging. 1995; 20: 395-405Crossref PubMed Scopus (22) Google Scholar This was followed by a remarkable series of technical innovations in catheter design to allow selective imaging of vascular structures and selective venous sampling, including measurement of renal vein renin levels.13.Rossi G.P. Cesari M. Chiesura-Corona M. et al.Renal vein renin measurements accurately identify renovascular hypertension caused by total occlusion of the renal artery.J Hypertens. 2002; 20: 975-984Crossref PubMed Scopus (23) Google Scholar Initial success at surgically restoring renal function after acute occlusion was followed by attempts to treat RAS to improve blood pressure control. Detailed studies of individual kidney function based on measuring inulin clearance and para-aminohippurate testing could identify when blood flow to the kidney had been reduced sufficiently to reduce urine flow and increase sodium reabsorption, but continue to have glomerular filtration.14.Stamey T.A. Nudelman J.J. Good P.H. et al.Functional characteristics of renovascular hypertension.Medicine (Baltimore). 1961; 40: 347-394Crossref PubMed Google Scholar The potential morbidity—and mortality—associated with renal artery surgery also led to concerns about the risks of surgical reconstruction and emphasized the need to carefully select patients who might benefit. In this context, early studies supported by the National Institutes of Health were undertaken to define clinical features, optimal imaging, diagnostic patterns, and outcomes of surgery for renovascular disease.15.Simon N. Franklin S.S. Bleifer K.H. et al.Clinical characteristics of renovascular hypertension.JAMA. 1972; 220: 1209-1218Crossref PubMed Google Scholar, 16.Bookstein J.J. Maxwell M.H. Abrams H.L. et al.Cooperative study of radiologic aspects of renovascular hypertension: bilateral renovascular disease.JAMA. 1977: 1706-1709Crossref Google Scholar, 17.Franklin S.S. Young J.D. Maxwell M.H. et al.Operative morbidity and mortality in renovascular disease.JAMA. 1975; 231: 1148-1153Crossref PubMed Google Scholar This landmark study provided a registry of more than 500 patients, but was limited by the lack of sampling for pressor hormones of the renin–angiotensin system. These studies provided a series of seminal papers regarding clinical features and comorbidity with atherosclerotic renal arterial disease.17.Franklin S.S. Young J.D. Maxwell M.H. et al.Operative morbidity and mortality in renovascular disease.JAMA. 1975; 231: 1148-1153Crossref PubMed Google Scholar These studies also identified a mortality risk above 6% associated with aortic surgery that limited the range of candidates most centers would consider for surgery. Renovascular surgery became a highly specialized clinical skill limited to high-volume centers with focused interest, as Novick18.Novick A.C. Management of renovascular disease: a surgical perspective.Circulation. 1991; 83: I167-I171PubMed Google Scholar reviewed. It remains so today. In view of the complexity and potential risks, the decision to undertake surgical revascularization routinely included multiple clinicians, including hypertension specialists, nephrologists, cardiovascular specialists, radiologists, and surgeons. Determining the likelihood of clinical improvement in blood pressure control was an overriding concern, more so than any potential recovery of kidney function. In the 1970s, measurement of the putative pressor signal for renovascular hypertension, plasma renin activity, became widely available and led to a series of seminal papers regarding lateralization of renin secretion from the affected kidneys,19.Maxwell M.H. Marks L.S. Lupu A.N. et al.Predictive value of renin determinations in renal artery stenosis.JAMA. 1977; 238: 2617-2620Crossref PubMed Google Scholar contralateral suppression of renin release, and additional maneuvers to reveal the role of the renin–angiotensin system for individual patients.20.Vaughan E.D. Buhler F.R. Laragh J.H. et al.Renovascular hypertension: renin measurements to indicate hypersecretion and contralateral suppression, estimate renal plasma flow and score for surgery.Am J Med. 1973; 55: 402-414Abstract Full Text PDF PubMed Scopus (135) Google Scholar Early experiences with surgical revascularization cast doubt that patients with reduced glomerular filtration rate (GFR) would gain much benefit regarding blood pressure control from restoring blood supply. Such patients were routinely excluded from consideration for renovascular surgery, based on both experimental and clinical data suggesting that parenchymal damage to the ‘contralateral’ kidney opposite the stenotic kidney would obviate a benefit regarding blood pressure control.21.Palmer J.M. Prognostic value of contralateral renal plasma flow in renovascular hypertension.JAMA. 1971; 217: 794-802Crossref PubMed Google Scholar Remarkably, the concept that chronic vascular occlusion might be a reversible cause of renal insufficiency surfaced only in the 1980s, and was greeted with skepticism.22.Novick A.C. Pohl M.A. Schrieber M. et al.Revascularization for preservation of renal function in patients with atherosclerotic renovascular disease.J Urol. 1983; 129: 907-912Abstract Full Text PDF PubMed Google Scholar,23.Schreiber M.J. Pohl M.A. Novick A.C. Preserving renal function by revascularization.Annu Rev Med. 1990; 41: 423-429Crossref PubMed Google Scholar Recognition that atherosclerotic disease poses a risk of progressive vascular occlusion that could be stabilized or reversed regarding renal failure gradually led some centers to shift from ‘cure of hypertension’ to ‘preservation of renal function’ as a primary indication for revascularization.24.Schreiber M.J. Pohl M.A. Novick A.C. The natural history of atherosclerotic and fibrous renal artery disease.Urol Clin North Am. 1984; 11: 383-392PubMed Google Scholar,25.Novick A.C. Atherosclerotic ischemic nephropathy.Urol Clin North Am. 1994; 21: 195-200PubMed Google Scholar Identification of the concept of ‘critical perfusion pressure’ for continued renal function that could be reversed by restoring renal blood flow supported this premise.26.Textor S.C. Novick A. Tarazi R.C. et al.Critical perfusion pressure for renal function in patients with bilateral atherosclerotic renal vascular disease.Ann Intern Med. 1985; 102: 309-314Crossref Google Scholar Several authors raised the possibility that unsuspected atherosclerotic renal arterial occlusion may contribute to advancing renal insufficiency more commonly than previously thought and coined the term ‘ischemic nephropathy.’27.Jacobson H.R. Ischemic renal disease: an overlooked clinical entity.Kidney Int. 1988; 34: 729-743Abstract Full Text PDF PubMed Google Scholar, 28.Breyer J.A. Jacobson H.R. Ischemic nephropathy.Curr Opin Nephrol Hypertens. 1993; 2: 216-224Crossref PubMed Google Scholar, 29.Scoble J.E. Maher E.R. Hamilton G. et al.Atherosclerotic renovascular disease causing renal impairment- a case for treatment.Clin Nephrol. 1989; 31: 119-122PubMed Google Scholar, 30.Scoble J.E. Hamilton G. Atherosclerotic renovascular disease: remediable cause of renal failure in the elderly.BMJ. 1990; 300: 1670-1671Crossref PubMed Google Scholar, 31.O’neil E.A. Hansen K.J. Canzanello V.J. et al.Prevalence of ischemic nephropathy in patients with renal insufficiency.Am Surg. 1992; 58: 485-490PubMed Google Scholar In 1978, Gruentzig et al.32.Gruentzig A. Kuhlmann U. Vetter W. et al.Treatment of renovascular hypertension with percutaneous transluminal dilatation of a renal artery stenosis.Lancet. 1978; 1: 801-802Abstract PubMed Google Scholar,33.Kuhlmann U. Gruentzig A. Vetter W. et al.Percutaneous translumial dilatation: a new treatment of renovascular hypertension?.Klin Wochenschr. 1978; 56: 703-707Crossref PubMed Scopus (0) Google Scholar extended the practice of peripheral vascular dilation to the kidney in a seminal paper on renal artery balloon angioplasty, followed a year later by a description of initial experience with renal artery angioplasty in the United States.34.Katzen B.T. Chang J. Knox W.G. Percutaneous transluminal angioplasty with the Gruntzig balloon catheter. A review of 70 cases.Arch Surg. 1979; 114: 1389-1399Crossref PubMed Google Scholar Subsequent reports confirmed the potential for renal artery angioplasty to improve management of uncontrolled hypertension.35.Sos T.A. Saddekni S. Sniderman K.W. et al.Renal artery angioplasty: techniques and early results.Urol Radiol. 1981; 3: 223-231Crossref PubMed Scopus (0) Google Scholar,36.Tegtmeyer C.J. Ayers C.A. Wellons H.A. The axillary approach to percutaneous renal artery dilatation.Radiology. 1980; 135: 775-776Crossref PubMed Google Scholar Technical success for angioplasty was generally good.37.Canzanello V.J. Millan V.G. Spiegel J.E. et al.Percutaneous transluminal renal angioplasty in management of atherosclerotic renovascular hypertension: results in 100 patients.Hypertension. 1989; 13: 163-172Crossref PubMed Google Scholar An obvious major benefit from these endovascular techniques was the potential for restoring kidney blood flow for many patients for whom the risks of surgical revascularization would be otherwise prohibitive. One shortcoming of renal artery angioplasty was the tendency for elastic recoil to occur, which narrowed the lumen again immediately after balloon dilatation. This posed a major problem for ostial lesions, which usually develop as an extension of aortic plaque into the renal artery. To prevent elastic recoil after angioplasty, Palmaz and colleagues in 1987 developed expandable metallic stents for renal arteries in a porcine model.38.Palmaz J.C. The current status of vascular intervention in ischemic nephropathy.J Vasc Interv Radiol. 1998; 9: 539-543Abstract Full Text PDF PubMed Google Scholar Initial reports of stents being placed in the renal artery in patients were positive.39.Mali W.P. Follow-up of endovascular stented renal artery.Am J Roentgenol. 1990; 154: 902Crossref PubMed Google Scholar,40.Joffre F. Bernadet P. Rousseau H. et al.Usefulness of a percutaneous endoprosthesis in the treatment of renal artery stenoses.Arch Mal Coeur Vaiss. 1989; 82 (1204): 11991Google Scholar These were followed by evaluation of the Palmaz stent in a clinical study,41.Rees C.R. Palmaz J.C. Becker G.J. et al.Palmaz stent in atherosclerotic stenoses involving the ostia of the renal arteries: preliminary report of a multicenter study.Radiology. 1991; 181: 507-514Crossref PubMed Google Scholar followed by a randomized trial comparing angioplasty with stenting that established significantly higher primary patency rates with the use of stents.42.van de Ven P.J. Kaatee R. Beutler J.J. et al.Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial.Lancet. 1999; 353: 282-286Abstract Full Text Full Text PDF PubMed Scopus (492) Google Scholar Today, primary stent placement for ostial RAS has become the standard (Figure 1a and b). Since the original description of the procedure, additional improvements in the technology have occurred, including the development of low-profile catheters and semicompliant balloon technology.43.Nolan B.W. Schermerhorn M.L. Rowell E. et al.Outcomes of renal artery angioplasty and stenting using low-profile systems.J Vasc Surg. 2005; 41: 46-52Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar The original balloon catheters were constructed on a larger platform (0.038inches), but are currently being delivered using smaller (0.014inches) guidewire technology. These lower-profile catheters help reduce periprocedural complications including embolization and vessel dissection that can occur during the introduction of the stent across the stenosis. Restenosis of treated vessels has been a practical limitation. Typically, one renal artery supplies each kidney and most renal arteries are 5mm in diameter or larger. A recent study using computed tomography angiography of the renal arteries demonstrated that 30% of patients have more than one renal artery supplying each kidney and that the average renal artery diameter is 5.6 to 6.0mm.44.Thatipelli M.R. Sabater E.A. Bjarnason H. et al.CT angiography of renal artery anatomy for evaluating embolic protection devices.J Vasc Interv Radiol. 2007; 18: 842-846Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Restenosis rates for stents placed in vessels >5mm in diameter are 15–20% at 9 months when measured by duplex ultrasound.45.Bakker J. Beutler J.J. Elgersma O.E. et al.Duplex ultrasonography in assessing restenosis of renal artery stents.Cardiovasc Intervent Radiol. 1999; 22: 468-474Crossref PubMed Scopus (49) Google Scholar,46.Girndt M. Kaul H. Maute C. et al.Enhanced flow velocity after stenting of renal arteries is associated with decreased renal function.Nephron Clin Pract. 2007; 105: c84-c89Crossref PubMed Scopus (7) Google Scholar Target vessel restenosis warranting reintervention for clinical indications such as recurrent hypertension, deteriorating kidney function (rise in creatinine by more than 20%), or recurrent pulmonary edema developed in 88 of 877 arteries (10.0%) from 748 patients followed longitudinally for a mean of 46 months.47.Bates M.C. Rashid M. Campbell J.E. et al.Factors influencing the need for target vessel revascularization after renal artery stenting.J Endovasc Ther. 2007; 13: 569-577Crossref Scopus (24) Google Scholar Vessels <5mm were twice as likely to restenose as compared with larger vessels.48.Sapoval M. Zharinger M. Pattynama P. et al.Low-profile stent system for treatment of atherosclerotic renal artery stenosis: the GREAT trial.J Vasc Interv Radiol. 2005; 16: 1195-2002Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Other predictors for restenosis include advanced age, a solitary functioning kidney, and extensive peripheral vascular disease. Restenosis for symptomatic patients after stent placement can be treated by restenting or with angioplasty. Newer technologies continue to be developed, such as drug-eluting stents (DESs), drug-coated balloons, and cutting balloons.49.Misra S. Sturludottir M. Matthews V. et al.Treatment of complex stenoses involving renal artery bifurcations using drug-eluting stents.J Vasc Interv Radiol. 2008; 19: 272-278Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar, 50.Misra S. Thatipelli M.R. Hunt C. et al.Preliminary study of the use of drug-eluting stents in atherosclerotic renal artery stenoses 4 mm in diameter or smaller.J Vasc Interv Radiol. 2008; 19: 833-839Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 51.Zeller T. Sixt S. Rastan A. et al.Treatment of reoccurring instent restenosis following reintervention after stent-supported renal artery angioplasty.Catheter Cardiovasc Interv. 2007; 70: 296-300Crossref PubMed Scopus (38) Google Scholar DESs have been available to treat coronary arteries since early 2000.52.Morice M.C. Serruys P.W. Sousa J.E. for RAVEL Study Group et al.A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization.N Engl J Med. 2002; 346: 1773-1780Crossref PubMed Scopus (3235) Google Scholar The major advantage of DESs is reduced risk for restenosis when compared with bare-metal stents, particularly in smaller vessels. Several groups have used DESs in small-diameter vessels such as accessory renal arteries, and some have observed patency rates of 70% in an average vessel diameter of 3.5mm as compared with 47% with bare-metal stents.53.Misra S. Thatipelli M.R. Howe P.W. et al.Preliminary study of the use of drug-eluting stents in atherosclerotic renal artery stenoses 4 mm in diameter or smaller.J Interv Radiol. 2008; 19: 833-839Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Some trials have not observed major benefits from DESs.54.Zahringer M. Sapoval M. Pattynama P.M. et al.Sirolimus-eluting versus bare-metal low profile stent for renal artery treatment (GREAT Trial): angiographic follow-up after 6 months and clinical outcome up to 2 years.J Endovasc Ther. 2007; 14: 460-468Crossref PubMed Scopus (68) Google Scholar,55.Kiernan T.J. Yan B.P. 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- W1991906068 title "Percutaneous revascularization for ischemic nephropathy: the past, present, and future" @default.
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