Endovascular treatment of renal artery stenosis (RAS)
Arterial hypertension and RAS
There is a Cochrane review from 2014 addressing the question of balloon angioplasty, with and without stenting, versus drug treatment in patients with arterial hypertension and RAS [1]. Based on the results of 7 randomised trials with more than 2000 participants reporting on cardiovascular and renal clinical outcomes, no differences could be established in this respect between angioplasty and drug treatment. However, the Cochrane review found that balloon angioplasty led to a small improvement in diastolic blood pressure and a slight reduction in the need for antihypertensives. Balloon angioplasty was classified as a safe procedure and was reported to result in a similar number of cardiovascular and renal adverse events as drug treatment.
A further interpretation of the studies available to date was provided by Mohan and Bourke in 2015 [2]. According to their systematic review, intervention is warranted in cases including:
- Patients with RAS >80% and a 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 rather than stenosis at the ostium
- Patients with rapid deterioration of renal function
- Renal artery stenosis in a transplant kidney.
The most comprehensive presentation to date of treatment outcomes in RAS was published by the Agency for Healthcare Research and Quality (AHRQ) in 2016.[3] This systematic review with comparative effectiveness analysis of drug treatment, revascularization by PTA + stenting (PTAS), and surgical revascularization in patients with arteriosclerotic renal artery stenosis included 78 studies and 20 case series published through March 2016. According to the authors, evidence from controlled trials suggests that PTAS offers no benefit compared with drug treatment alone in patient groups in which both interventions were compared in a balanced manner. Observational studies suggest that patients with an extended PTAS indication - particularly poorer renal function (variously defined) or higher blood pressure (also variously defined) - are more likely to achieve 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. Ultimately, there is a subset of patients who benefit from revascularization, but the evidence does not allow these to be clearly defined, except that case series demonstrate that some patients with acute decompensation do benefit from revascularization. The AHRQ review shows how differently the assessments turn out depending on whether the evidence came from a controlled trial, observational studies, or merely case series.
The question of the extent to which stenting is of clinical benefit in arteriosclerotic RAS was investigated in the randomized controlled Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial.[4] The trial enrolled a total of 947 participants who either had systolic hypertension in severe RAS with optimal drug treatment or had severe RAS combined with chronic kidney disease. Over a mean follow-up period of 43 months, no significant differences were found 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 group and patients treated by medication alone. The authors concluded that stenting of an arteriosclerotic RAS offers no clinical benefit if patients receive adequate drug treatment.
Another analysis of the CORAL trial investigated the effect of stenting on the estimated glomerular filtration rate (eGFR) in patients with RAS over 3 years [5]. It was able to demonstrate that stenting did not affect the eGFR in patients with RAS receiving therapy based on renin-angiotensin system inhibition. Stent treatment neither improved nor worsened renal function in patients with concurrent optimal medical treatment, and stent treatment did not modify the risk of clinically unfavourable events associated with chronic kidney disease.
A further analysis of the CORAL trial sought subgroups of patients who might benefit better from stent placement than the overall cohort [6]. The data from the CORAL trial did not reveal any benefit of stenting on the basis of degree of stenosis, haemodynamic significance of the lesion, or higher baseline blood pressure.
Ischaemic nephropathy and RAS
Ischaemic nephropathy is one of the more common causes of progressive chronic renal failure, which may lead to end-stage renal disease. It is usually caused by higher-grade arteriosclerotic bilateral RAS or unilateral stenosis in a functional single kidney (luminal narrowing of at least 70%); other causes such as fibromuscular dysplasia are rare [7, 8].
The finding of bilateral RAS or unilateral stenosis in a functional single kidney does not necessarily imply ischaemic nephropathy, since despite stenosis renal function is not impaired in every case. Ischaemic nephropathy is usually not diagnosed until there is progressive loss of renal function in the presence of proven stenosis, for which other causes have been excluded (e.g. diabetic nephropathy). The clinical picture is therefore a clinical diagnosis underpinned by diagnostic imaging but does not require histopathological evidence [8]. Angiography usually demonstrates a proximal or ostial bilateral renal artery stenosis as well as marked arteriosclerotic mural changes in the region of the abdominal aorta.
Ischaemic nephropathy is a disease of the elderly patient. Its prevalence in the international literature ranges from 1.9% to 27% [9, 10, 11, 12, 13]. Data from the United States Renal Data System show that the incidence rate of ischaemic 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 ischaemic nephropathy include older age, hypertension, nicotine abuse, diabetes mellitus, and hyperlipidaemia.
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 of around 70-80% and above results in a drop in perfusion pressure, which is accompanied by cortical hypoxia. This leads to rarefaction of the microvessels and, via complex mechanisms, irreversible interstitial fibrosis of the affected kidney.[16, 17] Perfusion-independent mechanisms expose the non-stenosed or marginally stenosed contralateral kidney to increased systemic pressure.[18]
The 5-year mortality of patients with ischaemic nephropathy is reported to be almost 50%.[10, 19] If patients require dialysis because of ischaemic nephropathy, the 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 revascularisation, renal function does not improve in every case.
If optimised drug treatment over weeks and months proves unsuccessful, a revascularising procedure may be performed in individual cases after careful consideration, provided that a 70% luminal narrowing is present.[22] Percutaneous stent angioplasty and the various types of surgical vascular reconstruction have been established revascularising measures for years.[23] Candidates for consideration are patients with:
- progressive chronic renal failure in the preceding 6-12 months [24],
- recurrent pulmonary oedema of non-cardiac origin (esp. bilateral stenosis, stenosed single kidney or transplant artery) [25, 26],
- refractory hypertension, even in the absence of impaired renal function (at least 3 antihypertensives including a diuretic) [27].
In about 25-30% of cases, revascularisation leads to an improvement up to normalisation of renal function; in about 50% of cases it remains stable, and in the remaining 20% of patients a deterioration up to dialysis dependence is observed.[23]
RAS due to fibromuscular dysplasia (FMD)
FMD involves a fibrotic thickening of the arterial wall, which may arise in the renal arteries but also in the arteries of the extremities and in the mesenteric and cerebral arteries, and may result in stenosis.[28] Most commonly affected are the renal arteries, and here in particular the right renal artery.[29] Young women below the age of 35 are disproportionately affected.[29, 30] FMD may explain acutely deteriorating hypertension in young individuals. The cause of the disease is unknown.
Endovascular treatment of FMD-mediated RAS by PTA has good technical success rates; however, a quarter of patients show signs of restenosis after 6 months to 2 years. The surgical treatment of these pretreated patients shows no worse outcomes than in patients without such prior treatment.[31]