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Revascularization in atherosclerotic renovascular disease: Problems beyond the obstruction

2006; Elsevier BV; Volume: 70; Issue: 5 Linguagem: Inglês

10.1038/sj.ki.5001765

1523-1755

Alejandro Chade,

Peripheral Artery Disease Management

The main goal in the treatment of obstructive atherosclerotic renovascular disease (ARVD) is to preserve or recover renal function. The ARVD kidney continues to deteriorate in 20–40% of cases despite restoration of blood flow. Holden et al. report that renal function stabilized or improved in up to 97% of patients with the use of a distal embolic protection device. The main goal in the treatment of obstructive atherosclerotic renovascular disease (ARVD) is to preserve or recover renal function. The ARVD kidney continues to deteriorate in 20–40% of cases despite restoration of blood flow. Holden et al. report that renal function stabilized or improved in up to 97% of patients with the use of a distal embolic protection device. The patient population with end-stage renal disease has been growing at a rate of 8%–14% per year for the past two decades.1.United States Renal Data System.in: 2005 Annual Data Report: Atlas of End-Stage Renal Disease in the United States National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA2005Google Scholar In almost one-third of those cases, atherosclerotic renovascular disease (ARVD) has been the cause of end-stage renal disease. Atherosclerotic lesions account for more than 90% of cases of renal artery lesions and are the cause of end-stage renal disease in up to 27% of patients over 45 years of age at the start of dialysis. The main goal in the treatment of obstructive ARVD is to recover or preserve renal function. Underlining this concept is the notion that ARVD is a progressive disorder. Major advances in revascularization techniques have emerged during the past 20 years. Percutaneous transluminal renal angioplasty (PTRA) and stenting have become the common treatments for patients with clinically significant renal artery stenosis and reversible renal disease. PTRA has a high success rate, long-term patency, and a low complication rate. Nevertheless, these treatments often fail to improve blood pressure or renal function despite successful renal revascularization. Post-PTRA deterioration of renal function may occur in 20–40% of patients, which limits the immediate benefits of the technique.2.Henry M. Henry I. Polydorou A. et al.Renal angioplasty and stenting: long-term results and the potential role of protection devices.Expert Rev Cardiovasc Ther. 2005; 3: 321-334Crossref PubMed Scopus (28) Google Scholar Indeed, the complex nature of ARVD, marked by deterioration of renal function and increasing morbidity and mortality of cardiovascular disease, is the impetus for ongoing clinical studies seeking adequate therapy (for example, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL), Regional Angiogenesis with Vascular Endothelial Growth Factor (RAVE), and Prospective Randomized Study Comparing Renal Artery Stenting (RESIST) trials). Angioplasty and stenting of the renal atherosclerotic lesion constitute the most emboligenic part of the procedure as demonstrated both in vivo3.Holden A. Hill A. Jaff M.R. Pilmore H. Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy.Kidney Int. 2006; 70: 948-955Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar,4.Henry M. Henry I. Klonaris C. et al.Renal angioplasty and stenting under protection: the way for the future?.Catheter Cardiovasc Interv. 2003; 60: 299-312Crossref PubMed Scopus (121) Google Scholar and ex vivo.5.Hiramoto J. Hansen K.J. Pan X.M. et al.Atheroemboli during renal artery angioplasty: an ex vivo study.J Vasc Surg. 2005; 41: 1026-1030Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar Tsao et al.6.Tsao C.R. Lee W.L. Liu T.J. et al.Delicate percutaneous renal artery stenting minimizes postoperative renal injury and protects kidney in patients with severe atherosclerotic renal artery stenosis and impaired renal function.Int Heart J. 2005; 46: 1061-1072Crossref PubMed Scopus (7) Google Scholar treated significant ARVD with delicate PTRA plus stenting without distal protection. This approach requires minimal device manipulation in both the pre-dilatation and the stenting stages to minimize potential injuries to dilated vessels as well as vessels distal to the obstruction due to atheroembolism. In the study, more than 90% of the patients stabilized or improved their renal function (results similar to those reported by Holden et al.3.Holden A. Hill A. Jaff M.R. Pilmore H. Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy.Kidney Int. 2006; 70: 948-955Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar in this issue) in the absence of any clinical signs or symptoms of atheroembolism. PTRA plus stenting, which showed major improvements in renal function, may offer an alternative treatment for ARVD, considering the challenge of using a distal protection device relative to its size or to renal artery anatomy. Nevertheless, this approach may not exclude the possibility of renal atheroembolism. Cholesterol emboli are thought to occur in approximately 50% of percutaneous interventions, most of them clinically silent.7.Mwipatayi B.P. Beningfield S.J. White L.E. et al.A review of the current treatment of renal artery stenosis.Eur J Vasc Endovasc Surg. 2005; 29: 479-488Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Furthermore, atheroemboli may not only occlude smaller vessels distal to the stenosis but may produce local vascular inflammation and cause substantial damage to the renal parenchyma. It is possible that atherogenic lipoproteins (for example, oxidized low-density lipoprotein) present in those debris as well as circulating cytokines may induce endothelial- and epithelial-cell dysfunction and vascular damage distal to the stenosis and infiltrate the mesangium and blood vessels,8.Abrass C.K. Cellular lipid metabolism and the role of lipids in progressive renal disease.Am J Nephrol. 2004; 24: 46-53Crossref PubMed Scopus (193) Google Scholar subsequently inducing secretion of growth factors that lead to glomerular and vascular remodeling and proliferation of extracellular matrix. It is worth noting that PTRA plus stenting is a delicate procedure that demands expertise by the operator, which may restrict its application. Holden et al.3.Holden A. Hill A. Jaff M.R. Pilmore H. Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy.Kidney Int. 2006; 70: 948-955Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar (this issue) address the potential problem of PTRA-induced embolisms in ARVD by reporting the results of a prospective study performed in patients with ARVD and blunted renal function (glomerular filtration rate below 50 ml per minute per 1.73 m2). They evaluated the impact on renal function using a dual therapeutic approach: aggressive balloon dilatation and stenting in combination with a distal embolic protection device. Preliminary results suggest the feasibility and safety of using distal protection devices during PTRA and stenting to protect the distal renal parenchyma against atheroembolism and renal-function deterioration.4.Henry M. Henry I. Klonaris C. et al.Renal angioplasty and stenting under protection: the way for the future?.Catheter Cardiovasc Interv. 2003; 60: 299-312Crossref PubMed Scopus (121) Google Scholar,9.Holden A. Hill A. Renal angioplasty and stenting with distal protection of the main renal artery in ischemic nephropathy: early experience.J Vasc Surg. 2003; 38: 962-968Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar On the other hand, limitations on the use of these devices include the characteristics of the atherosclerotic lesions (for example, tortuosity), anatomic variants of the renal arteries (for example, early branching), and reduced maneuverability of integrated filter-guidewire systems.10.Mauri L. Rogers C. Baim D.S. Devices for distal protection during percutaneous coronary revascularization.Circulation. 2006; 113: 2651-2656Crossref PubMed Scopus (54) Google Scholar The aggressive PTRA technique performed by Holden et al.3.Holden A. Hill A. Jaff M.R. Pilmore H. Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy.Kidney Int. 2006; 70: 948-955Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar (stent dilated up to 7 mm) may have improved kidney function if done without distal protection. Atheroembolic renal failure is one of the most common complications of PTRA, and the use of intrarenal distal protection devices may limit this risk. Therefore, the absence of a control group treated without embolic protection represents a limitation of the study.3.Holden A. Hill A. Jaff M.R. Pilmore H. Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy.Kidney Int. 2006; 70: 948-955Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar Indeed, the outcome of the ischemic kidney in ARVD is probably determined not only by narrowing of the large arteries but also by the prevention, or potential for reversibility of intrarenal small-vessel compromise. Atheroembolism to distal renal beds is more frequent when PTRA is performed on long critical lesions with a large atheroma load. Notably, Holden et al.3.Holden A. Hill A. Jaff M.R. Pilmore H. Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy.Kidney Int. 2006; 70: 948-955Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar found that macroscopic embolic material was present in 60% of the filters, and that renal function stabilized or improved in more than 90% of patients, an outcome that was more evident when baseline renal insufficiency was mild and recent. Furthermore, the study also showed a strikingly low rate of re-stenosis (8% of the patients) as compared with that found in the literature (15%–20%); this probably represents an additional benefit of this dual approach. Although these results seem promising, unresolved issues remain regarding the responses of the ARVD kidney to revascularization that are probably responsible for the 20%–40% of patients whose renal function continues to deteriorate (Figure 1). It is possible that part of the problem may be due to damage of the renal parenchyma, which can progress as ARVD evolves. The mixed responses to revascularization in ARVD are possibly related to existent and progressive renal damage distal to the stenosis, or as a consequence of intervention in up to 20% of cases. Deterioration of renal function in ARVD after intervention may not only represent an acute complication but also disclose deleterious mechanisms that progressively harm the ARVD kidney during the evolution of atherosclerosis. The consequences of this problem may be unmasked after an additional sudden insult. Therefore, minimizing the risk of potential complications such as atheroembolism should be considered in the treatment of the stenotic kidney. Therapeutic strategies such as those described by Holden et al.3.Holden A. Hill A. Jaff M.R. Pilmore H. Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy.Kidney Int. 2006; 70: 948-955Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar give us hope for rescuing the ischemic kidney and may bring us one step closer to defining an adequate therapeutic strategy to halt the progression of renal damage in patients with ARVD.