Endovascular treatment of renal artery stenosis (RAS)
Arterial hypertension and RAS
There is a Cochrane Review from 2014 comparing balloon angioplasty (with and without stenting) with drug treatment in patients with arterial hypertension and RAS.[1] Based on the reported cardiovascular and renal clinical outcomes of 7 randomized trials with more than 2000 patients, no differences were found between angioplasty and drug treatment. However, the Cochrane Review did reveal that balloon angioplasty improved diastolic blood pressure only mildly and reduced the need for antihypertensives only slightly. Balloon angioplasty was found to be a safe procedure and resulted in a similar number of cardiovascular and renal adverse events as drug treatment.
Mohan and Bourke provided another interpretation of the studies hitherto available in 2015.[2] According to their systematic review, intervention is warranted in cases including:
- Patients with RAS >80% and significant translesional pressure gradient
- Patients whose hypertension is difficult to control even with more than three antihypertensives, especially in younger patients
- Patients with truncal stenosis of the renal artery manifesting as stenosis at the ostium
- Patients with rapid deterioration of renal function
- Renal artery stenosis in kidney transplants
The most comprehensive presentation to date of treatment outcome in RAS was published by the Agency for Healthcare Research and Quality (AHRQ) in 2016.[3] This systematic review of studies published through March 2016 compared the efficacy of drug treatment, revascularization by PTA + stenting (PTAS), and surgical revascularization in patients with arteriosclerotic renal artery stenosis, including 78 studies and 20 case series. According to the authors, evidence from controlled trials suggested that PTAS offers no benefit compared with drug treatment alone in patient groups in which both interventional modalities were balanced. Observational studies suggest that patients with extended PTAS indication - particularly poorer renal function (defined differently) or higher blood pressure (also defined differently) - are more likely to experience improved renal function and improved blood pressure with PTAS. It remains unclear whether such "high-risk" patients benefit from PTAS in terms of survival, prevention of cardiovascular events, and renal replacement therapy compared with patients who remain on drug treatment. Finally, while there is a subset of patients benefitting from revascularization, the evidence does not clearly define this, except that case series demonstrate that some acutely decompensated patients do benefit from revascularization. The AHRQ review shows how assessments vary depending on whether the study was a controlled trial, observational study, or just a case series.
To what extent stenting is of clinical benefit in arteriosclerotic RAS was studied in the randomized controlled Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial.[4] The trial enrolled a total of 947 patients suffering either from systolic hypertension in severe RAS and optimized drug treatment or from severe RAS in chronic kidney failure. A mean follow-up period of 43 months revealed no significant differences in the combined end point (death from cardiovascular or renal causes; myocardial infarction; stroke; hospitalization for congestive heart failure; progressive renal failure; need for renal replacement therapy) between the stented treatment arm and patients treated by medication alone. The authors concluded that stenting in arteriosclerotic RAS does not offer clinical benefit if patients receive adequate drug treatment.
Another analysis of the CORAL trial studied the effect of stenting on estimated glomerular filtration rate (eGFR) in RAS patients after a follow-up of 3 years.[5] It revealed that stenting did not affect the eGFR in RAS patients receiving renin-angiotensin system inhibitors. Stenting in patients with optimized drug treatment neither improved nor worsened renal function, and also did not modify the risk of clinically unfavorable events associated with chronic kidney failure.
Another analysis of the CORAL trial focused on subgroups of patients who may have benefited better from stenting than the overall cohort.[6] Based on degree of stenosis, hemodynamic significance of the lesion, and higher baseline blood pressure, the data from the CORAL trial did not suggest any benefit of stenting.
Ischemic nephropathy and RAS
Ischemic nephropathy is one of the more common causes of progressive chronic renal failure, which may result in end-stage renal disease (ESRD). It is usually caused by higher-grade arteriosclerotic bilateral RAS or unilateral stenosis in functional single kidneys (luminal narrowing at least 70%); other causes such as fibromuscular dysplasia are rare.[7, 8]
The finding of bilateral RAS or unilateral stenosis in functional single kidney does not necessarily imply ischemic nephropathy because despite stenosis, renal function is not always impaired. Ischemic nephropathy is usually not diagnosed until there is progressive renal function loss in the presence of proven stenosis, for which other causes have been ruled out (e.g., diabetic nephropathy). Hence, the clinical picture amounts to a clinical diagnosis underpinned by diagnostic imaging and does not require histopathological evidence.[8] Angiography usually demonstrates proximal or ostial bilateral RAS and marked arteriosclerotic mural changes in the abdominal aorta.
Ischemic nephropathy is a disease of the elderly patient. In the international literature, its prevalence ranges from 1.9% to 27%.[9, 10, 11, 12, 13] Data from the United States Renal Data System show that the incidence of ischemic nephropathy more than doubled during the observation period from 1991 to 1997.[11] There is no more recent data available for Germany either. Risk factors for the development of ischemic nephropathy include older age; hypertension; nicotinic abuse; diabetes mellitus; and hyperlipidemia.
Arteriosclerotic changes in the renal artery usually follow a progressive course and may culminate in complete stenotic occlusion of the artery.[14, 15] Lumen narrowing by around 70-80% and above results in a drop in perfusion pressure, which is accompanied by cortical hypoxia. This leads to rarefaction of microvessels and, via complex mechanisms, irreversible interstitial fibrosis of the affected kidney.[16, 17] Mechanisms independent of perfusion expose the non-stenosed or marginally stenosed contralateral kidney to increased systemic pressure.[18]
The 5-year mortality of patients with ischemic nephropathy is reported to be almost 50%.[10, 19] If patients require dialysis because of ischemic nephropathy, 5-year mortality increases even further.[20, 21] In vascular surgery and soon after the introduction of endovascular procedures, it became clear that even with technically successful revascularization, renal function does not always improve.
If optimized drug treatment for weeks and months proves unsuccessful, revascularization in 70% luminal narrowing may be performed in some patients after careful consideration.[22] Long-standing procedures in revascularization include percutaneous stent angioplasty and the different types of surgical vascular repair.[23] Patients with the following conditions are candidates for consideration:
- Progressive chronic renal failure in the preceding 6-12 months [24]
- Noncardiac recurrent pulmonary edema (esp. bilateral stenosis, RAS in single/transplant kidneys [25,26])
- Refractory hypertension, even in the absence of impaired renal function (at least 3 antihypertensives including diuretic) [27]
In about 25-30% of cases, revascularization improves and even normalizes renal function; in about 50% of cases, it remains stable, and in the remaining 20% of patients, deterioration to the point of ESRD is observed.[23]
Fibromuscular dysplasia (FMD) with RAS
FDM involves fibrotic thickening of the arterial wall, which may arise in the renal arteries but also in the mesenteric and cerebral arteries and those of the extremities, resulting in stenosis.[28] Most commonly affected are the renal arteries, in particular the right renal artery.[29] Young women below age 35 are disproportionately affected.[29, 30] FMD may explain acutely deteriorating hypertension in young individuals. The cause of the disease is unknown.
While PTA of FMD-mediated RAS has good technical success rates, about 25% of patients show signs of restenosis after 6 months to 2 years. The surgical outcomes in pretreated patients are no worse than those in patients without such prior treatment.[31]