atherosclerotic renal artery hypertension is reported in almost 7% of adults older than 65 years1 ) and is associated with cardiovascular events , and may double risk of mortality2 ) . in the 1990s , radiological angioplasty began to replace surgical revascularization .
galaria et al . showed that percutaneous and open renal revascularization had equivalent long - term functional outcomes3 ) . over time , the less - invasive procedure became more accessible .
most cases of atherosclerotic renovascular disease ( arvd ) are located in the ostium , and are extensions of calcified aortic plaques4 ) .
stent placement might also provide additional force to increase the rates of technical success5 ) and to reduce the rate of restenosis at 6 months after the initial procedure6 ) .
intervention with stents has become a standard procedure ; in patients with stenosis of the renal artery , placement of a stent is likely to be the initial form of treatment .
however , there is limited evidence to support revascularization over medical therapy for patients with atherosclerotic renal artery stenosis7 , 8) .
retrospective studies previously reported that renal artery lesions might progress to severe stenosis and ultimately to renal artery occlusion9 ) .
michael et al . performed a prospective study that reported that the progression of renal artery disease was a frequent occurrence with an annual rate of progression of renal artery lesions reported to be 7%10 ) .
however , at the time of these studies , statins were being used in fewer patients .
a retrospective study of the effects of statins on the progression of arvd has shown that the use of statins reduces the risk of progression and the development of arvd11 ) .
another prospective population - based study reported that the progression to significant arvd was observed in only 4.0% during 8 years of follow - up ( annualized rate , 0.5% per year ) , and no case of arvd progressed to occlusion12 ) .
essential hypertension and clinically silent renal artery stenosis often coexist , and essential hypertension also coexists with renovascular hypertension13 ) .
renal injury distal to an atherosclerotic renovascular obstruction is due to multiple intrinsic factors producing parenchymal tissue injury ( fig .
non - traditional mediators of arvd such as inflammatory pathways , reactive oxygen species production , ischemia / reperfusion damage and modulation of matrix turnover have been proposed as causes of the renal failure related to arvd15 ) .
this complexity of the pathophysiology might explain why the severity of the stenosis is not correlated with renal dysfunction .
clinical data support dissociation of improved renal artery patency from clinical outcome in patients with atherosclerotic renal artery stenosis ; this may illustrate the effects of irreversible injury on the post stenotic kidney . a prospective clinical study reported by wright et al . showed absence of a correlation between renal artery anatomy and baseline renal function or functional outcome , and a good correlation between renal functional outcome and proteinuria
; these findings suggest that renal parenchymal damage is a major determinant of renal dysfunction and outcome rather than the severity of the renal artery stenosis in arvd16 ) .
reported that the mean arterial pressure did not decrease by 10 mmhg or more after revascularization and renal function declined in most patients with arvd that had high resistance - index values before revascularization17 ) .
chrysochou et al . showed a correlation between baseline proteinuria and decline in estimated glomerular filtration rate ( gfr ) with time after revascularization18 ) .
therefore , post stenotic renal injury can lead to renal parenchymal injury reflected by high intrarenal resistance and/or the presence of proteinuria .
proteinuria and other factors involved in intrarenal resistance are predictors of a poor outcome after renal revascularization in arvd
. when patients with chronic kidney disease undergo renal angioplasty with / without stent placement , the response with regard to renal function can be negative as well as positive .
positive responses include improvement of renal function , and stabilization or attenuation of declining renal function , as expected .
possible causes of these adverse outcomes include contrast induced nephropathy , atheroembolism , and restenosis or stent thrombosis19 )
. the administration of contrast might increase the risk of acute renal dysfunction , especially in patients that have preexisting renal impairment .
an ex vivo study reported that each manipulation of atheroma specimens , from simply advancing the guidewire through the atherosclerotic lesion to positioning and deploying the wallstent , releases thousands of fragments , and that these atherosclerotic fragments are of sufficient size to create vascular occlusion and initiate significant renal parenchymal damage20 ) .
the nature of this disorder suggests that a systemic approach is necessary to provide cardiovascular protection .
previously , statin therapy was discussed as a method of altering the natural history of arvd11 ) .
angiotensin - converting enzyme inhibitors and angiotensin receptor blockers effectively reduce blood pressure in patients with renovascular disease . in addition , a population - based cohort study of over 3,500 patients with arvd in canada found that angiotensin inhibitors could cause acute renal toxicity in a small subset of vulnerable patients ; however , they still improved the cardiovascular and renal outcomes in patients with arvd , but at the expense of acute renal toxicity21 ) . recently
three randomized controlled trials have been performed : the stent placement and blood pressure and lipid - lowering for the prevention of progression of renal dysfunction caused by atherosclerotic ostial stenosis of the renal artery ( star ) trial , the angioplasty and stenting for renal artery lesions ( astral ) trial , and the cardiovascular outcomes in renal artherosclerotic lesions ( coral ) trial ( table 1 ) .
two large randomized trials of intervention vs. medical therapy showed negative results for the intervention .
the star trial was a european multicenter trial that enrolled 140 patients with ostial renal artery stenosis greater than 50% , blood pressure controlled to less than 140/90 mmhg , and creatinine clearance 15 to 80 ml / min7 ) .
all patients received angiotensin blocking agents and a statin , regardless of their lipid levels .
after a 2-year interventional period , no difference was observed in the decline of renal function , the degree of blood pressure control , and the rates of cardiovascular morbidity and death .
investigators in the astral trial enrolled 806 patients with at least one stenotic renal artery considered suitable for balloon angioplasty , stenting , or both in their international , multicenter trial8 ) .
the mean estimated gfr was 40 ml / min , and most of the patients were on statin and angiotensin blocking therapy . at a mean follow - up of 33.6 months
, no difference was noted between the treatment groups in the decline of renal function or blood pressure control , and the renal function worsened slightly in both groups .
most of the enrolled patients in the two clinical trials had relatively asymptomatic atherosclerotic renal artery stenosis .
therefore , the practice of indiscriminately performing revascularization , without strong evidence , is no longer acceptable .
the coral trial is an ongoing multicenter randomized controlled trial in the united states22 ) .
it is still enrolling patients that have drug - resistant hypertension or a gfr < 60 ml / min .
it is using a standardized medical protocol to control blood pressure , and embolic protection devices during procedures are encouraged .
thus far , intervention has not been recommended if renal function has remained stable over the past 6 to 12 months and if hypertension can be controlled medically . according to a clinical classification of atherosclerotic renal artery stenosis with guidelines for vascular intervention of surveillance published in 2008 by the atherosclerotic peripheral vascular symposium23 ) , additional recommendations favoring medical therapy were as follows : very advanced age and/or limited life expectancy , extensive co - morbidities that make revascularization too risky , high risk for or previous experience with atheroembolic disease , and other concomitant renal parenchymal diseases that cause progressive renal dysfunction ( e.g. , interstitial nephritis , diabetic nephropathy)23 ) .
they also recommended factors favoring medical therapy and intervention as follows : progressive decline in gfr during treatment of systemic hypertension , failure to achieve adequate blood pressure control with optimal medical therapy ( medical failure ) , rapid or recurrent decline in the gfr in association with a reduction in systemic pressure , decline in the gfr during therapy with angiotensin - converting enzyme inhibitors or angiotensin receptor blockers , and recurrent congestive heart failure in a patient in whom the adequacy of left ventricular function does not provide an explanation23 ) .
the best evidence supporting intervention is for bilateral stenosis with " flash " pulmonary edema , but the evidence is from retrospective studies24 - 26 ) .
the aim of treatment for arvd should include the prevention of cardiovascular and/or renal events .
treatment of patients with arvd should include consideration of the following factors : age , co - morbidity , blood pressure , renal function , and kidney size .
the results of two recent studies suggest that patients with arvd and stable renal function can be controlled medically .
intervention should be considered only in patients with arvd and rapidly progressive cardiac or renal dysfunction .
the results of the coral and the post hoc analysis of astral might provide additional evidence for revascularization .
 atherosclerotic renovascular hypertension is a form of secondary hypertension due to renal artery stenosis . after the introduction of medical therapy such as with statins and angiotensin blocking agents 
 , it has been considered a very slowly progressive disease . in the 1990s , 
 surgical methods were compared to radiological intervention and showed no additional benefits . 
 recent clinical data also demonstrate that in cases of relatively stable atherosclerotic renovascular disease , medical therapy is as effective as other interventions with regard to patient outcomes . in this paper 
 the recent clinical outcomes are reviewed . 
Introduction
Natural history
Dissociation between arterial patency and function
Factors favoring medical therapy
Conclusion