Indications

The indications for renal artery revascularization are controversial in light of the absence of level I data demonstrating the efficacy of such therapy in improving adverse event–free survival among patients with renovascular disease. As described in Chapter 144, two recent clinical trials conducted in Europe, the ASTRAL (Angioplasty and Stenting for Renal Artery Lesions) trial¹¹ and the STAR (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) trial,¹² and the recently reported CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) trial^12a demonstrated no evidence to support the widespread application of renal stents to patients with renovascular hypertension or ischemic nephropathy. Both of the European trials have been criticized for methodologic shortcomings that limit the generalizability of their results and conclusions. Those limitations aside, the data presented in ASTRAL (and to a lesser extent in STAR) strongly suggest that the application of renal revascularization therapy to patients without strong clinical indications (i.e., prophylactic or “drive-by” revascularization) lacks demonstrable benefit for the patient. The results from the CORAL trial, which was more scientifically rigorous and robust, also demonstrated no clinical benefit for the widespread application to patients with renal artery stenosis and significant hypertension with or without associated renal dysfunction.

The initial results from the CORAL trial, also demonstrated no benefit from RA-PTAS in patients with significant hypertension with or without associated renal dysfunction. Although no interactions were observed for bilateral renal stenosis, degree of stenosis, or other clinical factors in terms of clinical benefit; additional analyses are planned for the CORAL data that may be of assistance in identifying patient subgroups more likely to benefit from RA-PTAS. Until those analyses are complete, guidance can be provided by existing consensus documents for severely affected patients or patients not representative of the CORAL study population. In general, those consensus reports state that decisions to perform renal revascularization should be based on the presence of hemodynamically significant renal artery stenosis in the setting of severe, difficult to control hypertension with or without associated renal dysfunction or in the setting of clinical congestive heart failure.¹⁴

Hypertensive indications and manifestations of renovascular disease include a spectrum of clinical presentations, such as chronic, severe hypertension that is refractory to pharmacologic management; renovascular hypertension associated with cardiovascular disturbance (especially in the setting of clinical congestive heart failure); and more acute hypertensive emergencies, which refer to acute blood pressure elevations associated with target organ damage, including flash pulmonary edema, hypertensive encephalopathy, myocardial infarction, and acute renal failure. Given the recent findings of ASTRAL and CORAL,¹¹ which demonstrated no reduction in adverse cardiovascular or renal events despite significant blood pressure decreases after RA-PTAS, as well as other large case series demonstrating a lack of survival benefit in association with blood pressure improvement alone,^5,7,8,15,16 many authorities on renovascular disease are advocating the application of renal revascularization to cases of truly refractory hypertension and those cases of hypertension complicated by defined end-organ effects.^17,18

Renal dysfunction in patients with hemodynamically significant atherosclerotic renovascular disease is commonly referred to as ischemic nephropathy,^3,19 although definitive establishment of a causal relationship between anatomic renovascular disease and renal dysfunction can be challenging in an individual patient despite extensive diagnostic testing. The diagnostic evaluation and pathophysiology of atherosclerotic renovascular disease are discussed in detail in Chapter 144. Conditions that would support a causative relationship between anatomically defined renal artery stenosis and disease manifestations are primarily based on reported predictors of response to intervention and include the precipitous decline in renal function during a short time, the severity of hypertension, and the presence of anatomic disease affecting perfusion to the entirety of the functioning renal mass (i.e., bilateral renovascular disease or renovascular disease affecting a solitary kidney).^7,20–24 In truth, though, a causative relationship can be proved only by a physiologic response after revascularization. Available data from numerous authors suggest that documented improvement in renal function after renal revascularization is the most important predictor of improvements in adverse event–free survival, suggesting that renovascular disease associated with renal dysfunction may represent the most appropriate contemporary indication for RA-PTAS.^5,7,25–27

Contraindications

Contraindications to the treatment of renovascular disease by endovascular means can be broadly classified into anatomic reasons, cases in which open revascularization is optimal, and prophylactic treatment. Anatomic contraindications involve situations in which the disease exists in renal arteries not easily treated with currently available endovascular devices or, more commonly, those arteries unable to be treated with any reasonable expectation of durable result. Renovascular disease extending into the terminal portion of a main renal artery and that involving a very short main renal artery represent two instances in which treatment with currently available technology may be a problem (Fig. 146-1). Renovascular disease existing in the branch arteries beyond the main bifurcation, lesions in multiple small renal arteries (Fig. 146-2), and lesions in children (most commonly hypoplastic lesions) are poor candidates for endovascular treatment because of durability concerns. When encountered, these situations are likely to be best treated with open surgical revascularization unless the patient represents a prohibitive surgical risk. Surgical revascularization is also preferred in patients with indications for renal revascularization who require open aortic surgery.

With regard to prophylactic revascularization, the high rate of technical success and low incidence of periprocedural complications associated with endovascular renal artery revascularization have led to increasingly aggressive application of this technique with rapid growth in utilization in recent years. There is currently no evidence supporting prophylactic renal revascularization (i.e., endovascular treatment of renal artery stenosis in patients with normal renal function and hypertension that is well controlled with conventional medical therapy). Furthermore, the results of ASTRAL,¹¹ the conduct of which approximated prophylactic treatment in a large percentage of its participants, confirmed the lack of efficacy for such an approach in terms of blood pressure control, renal function protection, reduction of cardiac events, or improved survival.

The natural history of atherosclerotic renal artery stenosis is associated with anatomic progression in only 10% to 30% of patients and progression to occlusion in 0% to 7%.^28–32 When anatomic disease progression does occur, it is not consistently associated with increases in blood pressure or serum creatinine concentration.³⁰ Considering the benign clinical course of asymptomatic renal artery stenosis in the majority of patients together with the risk of procedure-associated deterioration in renal function with intervention (discussed further later) and the recent results from the CORAL trial, we support a nonoperative, noninterventional management strategy for asymptomatic patients with anatomic renovascular disease and normal renal function and normal or easily controlled blood pressure.

Definitions of Success

Criteria for procedural technical success include reduction in stenosis as assessed by completion angiography and, when endoluminal stenting has been performed, complete coverage of the stenotic lesion by the deployed stent. Post-intervention residual stenosis of less than 30% has been suggested as a threshold for technical success versus failure.³³ When contrast angiography demonstrates anatomically successful treatment of the stenotic lesion, these findings should be further confirmed with transduced pressure measurement immediately proximal and distal to the treated lesion. We consider a persistent systolic pressure gradient of 10 mm Hg or more to be suggestive of inadequate treatment and will repeat angioplasty in this setting in the absence of a significant residual stenosis on the completion angiogram.

Whereas technical success implies delivery of the intended treatment with satisfactory anatomic and hemodynamic results, determination of whether patient benefit has been derived requires consideration of the indications for intervention and the clinical responses observed. Approaches to the assessment of hypertension response have evaluated systolic, diastolic, and mean blood pressure and a number of antihypertensive medications both as continuous outcome measures and in a categorical fashion using a combination of blood pressure and medication criteria.³³ The categorical definitions generally describe hypertension responses as cured, improved, or failed. Serum creatinine, cystatin C, estimated glomerular filtration rate (eGFR), and renal length and volume all represent continuous outcome measures indicative of renal function response to intervention. Categorization of renal response based on these measures has generally been determined as improved, unchanged, or worsened on the basis of post-intervention change within a predefined range. We have generally used an increase or decrease of 20% or more in eGFR to define improvement or worsening in renal function, respectively, with all other patients categorized as unchanged. Alternative analytic approaches have evaluated the impact of renal revascularization on the rate of decline in renal function, defining worsened or unchanged rates of eGFR decline as failure and attributing procedure-related benefit to patients experiencing improvement, stabilization, or slowed rate of decline in eGFR.

Unfortunately, none of the previously discussed parameters assesses the impact of intervention on patient morbidity or survival. Survival free from dialysis or cardiovascular morbidity represents an outcome that provides the most direct means of assessing the true benefit of intervention and likely represents the outcome of greatest importance in measuring the true value of renal revascularization to the patient.

Early Outcomes

Table 146-1 summarizes outcomes associated with primary RA-PTAS from select contemporary case series of adult patients.* Technical success rates ranged from 88% to 100% and exceeded 95% in the majority of reports. Periprocedural 30-day mortality was 0% to 5% in most recent series (Table 146-1). Procedure-related complications associated with RA-PTAS occurred in 0% to 43% of patients and were most commonly related to arterial access, contrast-induced nephropathy, or atheroembolization. In general, these early results mirror those of ASTRAL and STAR.^11,12

Survival

Long-term survival data for patients undergoing RA-PTAS are presently limited to retrospective studies and limited data from ASTRAL.¹¹ Dorros et al⁴⁷ observed a 74% 3-year survival rate after RA-PTAS; although renal failure was not a frequent cause of death, they observed decreased survival among patients with both baseline renal dysfunction and bilateral disease. Similar overall survival was reported by Kashyap et al,³⁴ who also observed a 63% rate of dialysis-free survival; lack of post-intervention improvement in renal function was associated with subsequent dialysis in that series. Similar relationships between baseline renal dysfunction, renal function response, and survival have been described by Kennedy et al.²⁶ Survival benefit associated with angiotensin-converting enzyme treatment⁷⁵ and statin use after RA-PTAS has also been described,^26,76 whereas preoperative congestive heart failure, coronary artery disease, and chronic obstructive pulmonary disease are additional factors that adversely affect post-intervention survival.^26,38,76

Similar data have come from ASTRAL and STAR.^11,12 In ASTRAL,¹¹ 5-year survival was 58% for the entire study sample, with no improvement demonstrated for those undergoing RA-PTAS. Improvement in diastolic blood pressure and reduced medication use observed for the stent arm participants were not demonstrated to have any effect on survival. As previously stated, no differences were observed in renal function, rate of renal function decline, or systolic blood pressure. In the results from STAR,¹² 2-year survival was slightly in excess of 80%, with no differences observed according to post-revascularization blood pressure control or renal function.