The presence of a renovascular abnormality alone does not translate directly into functional importance. Some degree of RVD can be identified in up to 20% to 45% of patients undergoing vascular imaging for other reasons, particularly coronary angiography or lower extremity peripheral vascular disease. ^, Most “incidentally detected” stenoses are of minor hemodynamic and/or clinical significance. The term “renovascular hypertension” refers to a rise in arterial pressure induced by reduced renal perfusion. A variety of lesions can lead to the syndrome of renovascular hypertension, some of which are listed in Box 47.1 . Studies of vascular obstruction using latex rubber casts indicate that between 70% to 80% of lumen obstruction must occur before changes in blood flow or pressure across the lesion can be detected. Measurements of pressure gradients during renal angiography confirm that a pressure gradient of at least 10 to 20 mm Hg between the aorta and poststenotic renal artery is required before measurable changes in renin release occur. ^, When advanced stenosis is present, the pressure and flow drop steeply as illustrated in Fig. 47.2 . When lesions have reached this degree of hemodynamic significance, they are deemed “critical” stenoses.

(A) Measured fall in arterial pressure and blood flow across stenotic lesions induced in experimental animals.

The degree of stenosis was determined using latex casts after completion of the experiment. These data indicate that “critical” lesions require 70% to 80% luminal obstruction before hemodynamic effects can be detected. (B) Effects of a balloon-induced, unilateral, controlled, graded stenosis (expressed as Pd/Pa ratio) on plasma renin concentration in the aorta ( green ), in the vein of the stenotic kidney ( blue ), and in the vein of the non-stenotic kidney ( red ). P _a , Aortic pressure; P _d , distal pressure.

A from May AG, Van de Berg L, DeWeese JA, et al. Critical arterial stenosis. Surgery . 1963;54:250–259; B from De Bruyne B, Manoharan G, Pijls NHJ, et al. Assessment of renal artery stenosis severity by pressure gradient measurements. J Am Coll Cardiol. 2006;48:1851–1855.

Upon developing critical stenosis, a series of events leads to a rise in systemic arterial pressure to restore renal perfusion pressure, as illustrated in Fig. 47.3 . One can view development of rising pressures in this context as an integrated renal response to maintain renal perfusion of the poststenotic kidney. It is important to distinguish between experimental models of “clip” stenosis, at which time a sudden change in renal perfusion is induced, and the more common clinical situation of gradually progressive lumen obstruction. In the latter instance, hemodynamic characteristics change slowly and are likely to produce hypertension over a prolonged time interval. The rise in systemic pressure restores normal renal perfusion, often with normal-sized kidneys and no discernible hemodynamic compromise. If the renal artery lesion progresses further (or is experimentally advanced), the cycle of reduced perfusion and rising arterial pressures repeats until malignant-phase hypertension develops.

Systemic arterial pressure (carotid) and poststenotic renal perfusion pressures (iliac) in an aortic coarctation model with a clip placed between the right and left renal arteries.

Measurements were obtained in conscious animals during development of renovascular hypertension. They illustrate the fact that despite a persistent gradient across the stenosis, renal perfusion pressure (inferred from Iliac pressure) returns to near normal levels as a result of systemic hypertension. A corollary of this pressure gradient is that reduction of systemic pressures lowers poststenotic perfusion pressures, sometimes below the range of autoregulation.

From Textor SC, Smith-Powell L. Post-stenotic arterial pressures, renal haemodynamics and sodium excretion during graded pressure reduction in conscious rats with one- and two-kidney coarctation hypertension. J Hypertens . 1988;6(4):311–319 with permission.

A corollary to “critical” arterial stenosis is that treatment aimed at normalization of elevated systemic pressures in renovascular hypertension reduces renal perfusion pressure beyond the stenotic lesion. Poststenotic pressures may fall to levels where autoregulation can no longer maintain blood flow. This underperfusion of the kidney activates counter-regulatory pathways and leads to a sequence of events again directed toward restoring kidney perfusion.

Reduction in renal perfusion pressures activates release of renin from juxtaglomerular cells within the affected kidneys. Animals genetically modified to lack the angiotensin 1 (AT1) receptor fail to develop 2-kidney-1 clip hypertension. This is illustrated in e Fig. 47.2 . Experiments using kidney transplantation from AT1 receptor knockout mice indicate that both systemic and renal angiotensin receptors participate in blood pressure regulation in additive fashion.

Systolic blood pressures in mice before and after placement of a renal artery clip in experimental two-kidney, one-clip renovascular hypertension (2K1C).

The rise in systolic blood pressure (SBP) after clip placement develops rapidly only in mice with an intact angiotensin 1A receptor (AT _1A+/+ ; blue circles, left panel ). This rise is blocked by administration of an angiotensin receptor blocker (red circles, left panel). A genetic knockout mouse strain with no AT1A receptor (AT _1A-/- ) has a lower SBP and no change after renal artery clipping (blue squares, right panel). No additional effect is noted with an angiotensin receptor blocker (red squares, right panel). These data reinforce the essential role of the renin-angiotensin system and an intact angiotensin 1 receptor for the development of renovascular hypertension.

Modified from Cervenka L, Horacek V, Vaneckova I, et al. Essential role of AT1-A receptor in the development of 2K1C hypertension. Hypertension. 2002;40:735–741.

The role of the renin-angiotensin axis in renovascular hypertension depends, in part, on whether or not a contralateral, nonstenotic kidney is present. Most human renovascular hypertension is considered analogous to 2-kidney-1-clip experimental (“Goldblatt”) hypertension (a clip is applied to one renal artery in the rat to cause stenosis, and the other renal artery is untouched). The contralateral, nonstenotic kidney is subjected to elevated systemic perfusion pressures. Rising perfusion pressure forces natriuresis from the nonstenotic kidney and suppresses renin release. Hence the nonstenotic kidney tends to prevent the rise in systemic pressures, thereby perpetuating reduced perfusion to the stenotic side and promoting continued renin release from the stenotic kidney. Hypertension in these models is angiotensin dependent and is associated with elevated circulating levels of plasma renin activity, as illustrated in Fig. 47.4 . The 2-kidney-1-clip model of renovascular hypertension provided the basis for many of the early functional studies of surgically curable hypertension in which side-to-side function was compared regarding glomerular filtration, sodium excretion, etc. It also forms the basis for comparing kidneys side to side using radionuclide studies, such as captopril renograms, and renal vein renin determinations.

Schematic view of two-kidney (A) and one-kidney (B) renovascular hypertension.

These models differ by the presence of a contralateral kidney exposed to elevated perfusion pressures in two-kidney hypertension. The nonstenotic kidney tends to allow pressure natriuresis to ensue and produces ongoing stimulation of renin release from the stenotic kidney. The one-kidney model eventually produces sodium retention and a fall in renin with minimal evidence of angiotensin dependence unless sodium depletion is achieved.

When no such contralateral kidney is present or able to respond to pressure natriuresis, the mechanisms sustaining hypertension differ. This corresponds to the 1-kidney-1-clip hypertensive model (the rat undergoes unilateral nephrectomy and clipping of the contralateral renal artery) ( Fig. 47.4B ). Although renin release occurs initially, elevated systemic pressures develop with sodium and volume retention due to ineffective natriuresis. Rising pressures eventually restore renin levels to normal. Hypertension in this model is not demonstrably dependent on angiotensin II unless prior sodium depletion is achieved. Clinical examples of this situation include bilateral renal artery stenosis (RAS) or stenosis in a solitary functioning kidney where the entire renal mass is affected, such as occurs with orthotopic renal transplants. In such cases, diagnostic comparison of side-to-side renin release is not possible or has little meaning.

Renin-Angiotensin System

The renin-angiotensin system has effects beyond its vasoconstrictor action in renovascular hypertension, ^, as illustrated in Fig. 47.5 . Activation of this system increases vascular resistance, sodium retention, and aldosterone stimulation. Complex interactions between angiotensin II and tissue and cellular systems occur, leading to vascular remodeling, left-ventricular hypertrophy, and activation of inflammatory and fibrogenic mechanisms.

Schematic view of activation of the renin-angiotensin system beyond a renal artery stenotic lesion.

Generation of circulating and local angiotensin II leads to widespread effects including sodium retention, efferent arteriolar vasoconstriction, and elevated systemic vascular resistance. Additional studies implicate angiotensin II in many other pathways of vascular and cardiac smooth muscle remodeling, activation of inflammatory and fibrogenic cytokines, coagulation factors, and induction of other vasoactive systems. ACE, Angiotensin-converting enzyme.

RVD also leads to disturbances in sympathetic nerve signaling, which may differ between 1-kidney and 2-kidney models. Muscle sympathetic nerve activity is increased in humans with renovascular hypertension, and blood pressure responses to adrenergic inhibition are amplified.

A major transition occurs with altered oxidative stress within the systemic vasculature, leading to increased oxygen free radicals. Experimental animals with 2-kidney-1-clip hypertension develop an increase in oxidative stress that can be reversed, in part, with angiotensin blockade and/or antioxidants. Some of these changes are reversible after revascularization in patients with both atherosclerotic and fibromuscular RVD. Studies in a swine model demonstrate an interaction between “atherosclerosis” induced by cholesterol feeding and RVD. ^, These data are supported by observations of a rise in nitric oxide (NO) and reduction in malondialdehyde within 24 hours of endovascular revascularization in atherosclerotic RVD. In some studies, oxidative stress can be reversed by both infusion of antioxidants and successful revascularization. Experimental infusion of agents that protect mitochondria from reactive oxygen species, by inhibiting opening of the mitochondrial transition pore, is associated with improved recovery of microvascular structures and renal function after revascularization.

The kidney, brain, and heart are all highly perfused with oxygenated blood. Yet unlike brain or cardiac tissue, oxygen extraction by the kidney is much lower, consistent with its function as a filtering organ. Under basal conditions, renal blood flow is among the highest of all organs reflecting its filtration function. Less than 10% of delivered oxygen is sufficient to maintain overall renal metabolic needs. The oxygen consumption that does occur within the kidney reflects solute transport. Measurements of both renal vein oxygen saturation and erythropoietin in patients with high-grade renovascular lesions indicate that whole organ “ischemia” is rarely present. The kidney maintains autoregulation of blood flow in the face of reduced arterial diameters of up to 75%. Imaging using blood-oxygen-level-dependent magnetic resonance (BOLD MR) demonstrates reduced oxygenation in deeper medullary regions in both normal kidneys and patients with RVD despite preserved cortical oxygenation. The renal medulla normally functions at levels close to hypoxia and is therefore sensitive to acute changes in perfusion. Studies of patients with RVD sufficient to reduce blood flow, kidney volume, and GFR indicate remarkable preservation of tissue oxygenation using BOLD MR. This stability of oxygen gradients is due partly to the surplus of oxygenated blood perfusing the cortex and to reduced oxygen consumption as a result of reduced solute filtration leading to reduced reabsorptive work of the affected kidney. When sufficiently severe, however, reduced blood flow leads to accumulation of deoxygenated molecular hemoglobin ( Fig. 47.7 ). ^,

Computed tomography angiogram (A) of high-grade vascular occlusion leading to left kidney atrophy while the right kidney is well perfused beyond an endovascular stent.

T2 signals from magnetic resonance imaging (B) illustrate a gradient of perfusion from cortex to lower levels in the deeper medullary sections, especially in the left kidney. Mapping of the blood-oxygen-level-dependent (BOLD) magnetic resonance R2∗ levels (a function of deoxyhemoglobin) (C and D) illustrates the normal gradient in the right kidney from cortex (low R2∗, blue) to deeper medullary segments that have progressively higher levels of R2∗ (green to red). The R2∗ map of the left kidney (D) illustrates overt cortical hypoxia evident beyond critical vascular occlusion associated with a larger fraction of the slice having high R2∗ values (red) associated with fractional medullary hypoxia.

More severe vascular occlusion produces both cortical and expanded medullary hypoxia as these adaptive measures are overwhelmed and tissue injury ensues. Eventually, structural atrophy of the renal tubules occurs, partly due to necrosis and apoptosis. The latter is an active, programmed cellular death that appears to be closely regulated and differs from tissue necrosis. Tubular atrophy is potentially reversible, and the kidney maintains the capacity for tubular cell regeneration under many conditions. These features support the concept that underperfused kidney tissue sometimes can achieve a “hibernating” state capable of restoring function if blood flow is restored. In late stages, histologic examination demonstrates reduced glomerular volume, loss of tubular structures near underperfused glomeruli, and areas of local inflammation as illustrated in e Fig. 47.5A and B .

(A) General clinical paradigm that a reduction in the renal blood flow related to hypoperfusion of the kidney can be reversible but can undergo a transition to irreversible injury eventually that no longer responds to restoration of blood flow alone. (B) Schematic depiction of the adaptation of tissue oxygenation in the kidney to moderate reductions in blood flow. Lowering renal blood flow by up to 30% to 40% in human subjects (right side) is associated with preservation of both oxygen gradients (lower graph) and tissue histology (upper images). The fact that such adaptation occurs partly explains the stability of kidney function during antihypertensive drug therapy that lowers systemic pressure and renal blood flow in patients with atherosclerotic renal artery stenosis. Eventually, more severe reductions of blood flow overwhelm “adaptation,” leading to overt tissue hypoxia (left side). (Magnification: low power: ×40.)

Modified from Gloviczki ML, Keddis MT, Garovic VD, et al. TGF expression and macrophage accumulation in atherosclerotic renal artery stenosis. Clin J Am Soc Nephrol. 2013;8(4):546–553; and Textor SC, Lerman LO. Paradigm shifts in atherosclerotic renovascular disease: where are we now? J Am Soc Nephrol. 2015;26:2074–2080.

A reduction in renal perfusion leads to diminished “shear stress” distal to the stenosis. This condition reduces production of NO and accelerates release of renin and generation of angiotensin II in the stenotic kidney. A direct consequence of reduced perfusion within the poststenotic kidney is progressive rarefaction of small vessels in both cortex and medulla, eventually producing tubular collapse ( eFig. 47.6 ). Glomerulosclerosis is a late event and usually reflects severe loss of glomerular filtration rate. Experimental studies infusing autologous endothelial progenitor cells and/or vascular endothelial growth factors (VEGF) into the renal artery demonstrate that functional recovery of GFR and restoration of vascular function can sometimes be achieved, suggesting that angiogenesis may be an achievable goal in this vascular bed. ^, Taken together, the kidney is subject to a wide variety of vasoactive and inflammatory mediators, which can be disturbed by loss of blood flow and perfusion pressure. These disturbances appear to activate a variety of fibrogenic and local destructive mechanisms, which can lead to irreversible parenchymal damage within the kidney. For further discussion of vasoactive and inflammatory molecules in the kidney, see Chapter 11.

Upper panels, Microcomputed tomography reconstructions of vessels in experimental atherosclerosis and superimposed large-vessel renovascular disease at an early stage (middle) and after chronic ischemia (right), compared with normal (left). Lower panels, Corresponding renal histology (trichrome stain ×400). Complex microvascular dysfunction and rarefaction develop in poststenotic kidneys. These are accelerated and/or modified by angiogenic stimuli, oxidative stress pathways, and a variety of cytokines, leading eventually to interstitial fibrosis. Studies in experimental animals suggest that angiogenic stimuli such as intrarenal infusion of endothelial progenitor cells or mesenchymal stem cells may offer the potential to repair microvascular injury. MV, Microvascular.

From Lerman LO, Chade AR. Angiogenesis in the kidney: a new therapeutic target? Curr Opin Nephrol Hyper. 2009;18:160–165.

As illustrated in e Fig. 47.6 , restoring renal perfusion can allow recovery of renal function if accomplished when these changes remain reversible. At some point, both inflammatory and fibrogenic mechanisms appear no longer to respond with recovery of renal function.

Manifestations of renal artery disease vary widely across a spectrum illustrated in Fig. 47.1 , Box 47.2 , and Table 47.2 . This spectrum ranges from an incidental finding noted during imaging for other indications to advancing renal failure leading to the need for dialytic support. As lesions progress to more severe levels of occlusion, hypertension develops and multiple manifestations may appear. As described earlier, multiple mechanisms raise systemic arterial pressure and tend to restore renal perfusion pressures to levels close to baseline. Table 47.2 summarizes clinical features associated with ARVD: short duration of hypertension, early age of onset, fundoscopic findings, hypokalemia, etc. Unfortunately, each in isolation has limited discriminatory or predictive value.

As renal artery lesions progress to critical stenosis, they can produce a rapidly developing form of hypertension, which may be severe and associated with polydipsia, hyponatremia, and central nervous system findings. Such cases are most often seen with acute renovascular events, such as sudden occlusion of a renal artery or branch vessel.

More commonly, RVD presents as progressive worsening of preexisting hypertension, often with a modest rise in serum creatinine. Since the prevalence of both hypertension and atherosclerosis increases with age, this disorder must be considered, particularly in older subjects with progressive hypertension. Some of the most striking examples of renovascular hypertension are older individuals whose previously well-controlled hypertension deteriorates with an accelerated rise in systolic blood pressure and target injury, such as stroke. Studies from hypertension referral centers in the Netherlands illustrate this. Of 477 patients undergoing detailed evaluation for RAS because of “treatment resistance,” 107 (22.4%) were identified with RVD (>50% stenosis by angiography). Ambulatory blood pressure recordings indicate exaggerated systolic pressure variability and frequent loss of the circadian pressure rhythm, commonly associated with left-ventricular hypertrophy. Sympathetic nerve traffic recordings indicate heightened adrenergic outflow. A population-based study of 870 subjects older than age 65 indicated that those with RVD had a twofold to threefold increased risk for adverse cardiovascular events during the subsequent 2 years.

Declining renal function during antihypertensive therapy is a common manifestation of progressive renal arterial disease. Not surprisingly, blood flow and perfusion pressures to the kidney fall distal to a “critical” RAS. This can be worsened by reduction in systemic pressure by any antihypertensive regimen. Reduced GFR during antihypertensive therapy has become particularly common since the introduction of ACE inhibitors and angiotensin receptor blockers. A precipitous rise in serum creatinine soon after starting these agents may occur due to decreases in glomerular hydrostatic pressure and accompanying loss of transcapillary filtration pressure produced by removing the efferent arteriolar vasoconstriction elicited by angiotensin II. This particular “functional” loss of GFR is reversible if detected promptly and should lead the clinician to consider large-vessel RVD when it occurs. ^, Clinically important changes in serum creatinine become apparent, mainly when the entire renal mass is affected, such as with bilateral RAS or stenosis to a solitary functioning kidney. Many of these patients tolerate reintroduction of renin-angiotensin blockade when challenged after successful revascularization.

Other syndromes heralding occult RAS are becoming more commonly recognized. Among the most important are rapidly developing episodes of circulatory congestion (“flash” pulmonary edema). This clinical scenario usually arises in patients with hypertension and left-ventricular systolic function, which may be well preserved. Underlying arterial compromise may favor volume retention and resistance to diuretics in such cases. A sudden rise in arterial pressure impairs cardiac function due to rapidly developing diastolic dysfunction. Such episodes tend to be rapid in both onset and resolution. Patients with treatment-resistant congestive cardiac failure, often with reduced arterial pressures, may also harbor unsuspected RVD. Restoration of renal blood flow in such patients can improve volume control and sensitivity to diuretics with lower risk of azotemia during therapy. A similar sequence of events may produce symptoms of “crescendo” angina from otherwise stable coronary disease. Registry data indicate that patients with episodic pulmonary edema with RVD have substantially increased hospitalization and mortality that can be reduced with successful revascularization. ^,

Another clinical presentation of RAS is advanced renal failure, occasionally at end-stage requiring kidney replacement therapy. Studies in patients with bilateral RAS indicate that reduction of systemic pressures to normal levels using sodium nitroprusside can abruptly reduce both renal plasma flow and glomerular filtration rate, indicating that the poststenotic pressures are at critical levels beyond autoregulation ( eFig. 47.4 ). Some estimates suggest that up to 12% to 14% of patients reaching end-stage kidney failure (ESKF) with no other identifiable primary renal disease may have occult, bilateral renal arterial stenosis. ^, A more conservative review of U.S. Renal Data Systems data for patients older than age 67 in the United States starting dialysis suggests that identified RVD may be present between 7.1% and 11.1% of patients, although clinicians caring for such patients attributed their renal failure to RVD in only 5.0%. Importantly, patients with rapidly progressive dysfunction and accelerated hypertension have the potential to recover kidney function and a mortality benefit from revascularization. ^{, ,} Such individuals were rarely included in prospective, randomized trials (see later).

The causal role of vascular impairment in producing renal dysfunction is established most firmly when renal revascularization leads to recovery of renal function. Unfortunately, this does not occur commonly. ^, A subset of patients with more severe or long-standing vascular occlusion (usually defined as peak systolic velocities >385 cm/sec on duplex ultrasound) manifest overt cortical hypoxia using BOLD MR. Such patients demonstrate more advanced tissue histologic injury with loss of tubular structures on biopsy and interstitial cellular infiltrates consistent with inflammatory injury ^, ( e Figs. 47.6 and 47.7 ) . These observations support the concept of transition from a primarily “hemodynamic” reduction in kidney function, one that may be improved by restoring blood flow, to inflammatory-mediated injury that no longer predictably recovers after restoration of vessel patency.

The potential benefit of revascularization regarding salvage, or at least stabilization, of renal function is greatest when serum creatinine is <3 mg/dL. Remarkably, RAS can be associated with proteinuria, occasionally to nephrotic levels. Proteinuria can diminish or resolve entirely following renal revascularization .Although poststenotic kidneys may lose GFR and tissue volume, the contralateral kidney without stenosis undergoes compensatory hypertrophy. These changes mask the damage to the affected kidney, making overall GFR an unreliable marker of the severity and progression of atherosclerotic RAS. ^, Most patients with episodic pulmonary edema have bilateral disease or a solitary kidney. Long-term mortality during follow-up is higher when bilateral disease is present, regardless of whether renal revascularization is undertaken ( eFig. 47.7 ).

Kaplan-Meier survival curve of 160 patients with more than 70% renal artery stenosis managed without revascularization.

Those with bilateral disease had lower survival, primarily due to associated cardiovascular disease. The mean age of death was 79 years. These data underscore the close relationship between the extent of vascular disease and mortality. Less than 10% of these subjects developed advanced kidney disease during follow-up, although long-term survival, even in treated patients, is related to levels of kidney function at the time of intervention. Recent prospective randomized clinical trials indicate that between 16% and 22% of medically treated patients with atherosclerotic renal artery stenosis progress to more advanced renal dysfunction over 3 to 5 years.

From Foster JH, Maxwell MH, Franklin SS, et al. Renovascular occlusive disease: results of operative treatment. JAMA. 975;2231:1043–1198; Textor SC. Renovascular hypertension and ischemic nephropathy. In: Skorecki K, Chertow GM, Marsden PA, et al, eds. Brenner and Rector’s: The Kidney. 10th ed. Philadelphia: Elsevier; 2016:1567–1609.

Atherosclerosis is a progressive disorder, although individual rates of progression vary widely ( Fig. 47.9 ). Clinical manifestations of RVD depend partly on the severity and extent of vascular occlusion. Zierler reported a 20% rate of RVD progression overall with 7% advancing to total occlusion over 3 years. A later report from the same group using different Doppler velocity criteria suggested higher rates of progressive stenosis. Data from medical treatment trials suggest that progressive occlusion can develop silently in up to 16% of treated subjects. These observations are supported by development of renal endpoints (defined as progressive renal deterioration) ranging between 16% and 22% in recent prospective RCTs (ASTRAL and CORAL).

Cumulative rates of anatomic disease progression in atherosclerotic renal artery stenosis, as measured by renal artery Doppler ultrasound.

During a follow-up period of 5 years, overall progression was 31%, but those with the most severe baseline lesion progressed in 60% of cases. The progression of vascular disease was not closely related to changes in serum creatinine or renal atrophy.

Modified from Radermacher J, Weinkove R, Haller H. Techniques for predicting a favourable response to renal angioplasty in patients with renovascular disease. Curr Opin Nephrol Hypertens . 2001;10(6):799–805.

Computed tomography (CT) angiograms illustrating reconstructed views of complex vascular disease.

(A) Aortic endovascular stent extending beyond the origins of the renal arteries. Renal artery stents have been placed through the aortic graft to restore blood flow, although the nephrograms demonstrate patchy defects consistent with small vessel occlusion and/or atheroembolic events. (B) illustrates a CT angiogram with a small aneurysm of the right renal artery that has produced segmental infarction, leading to accelerated hypertension. Although CT angiography requires contrast, current multidetector CT studies allow excellent image resolution at rapid acquisition and less contrast exposure than ever before.

Most series of medically treated patients indicate that despite evident progression of vascular disease, changes in kidney function are modest and uncommon. Results reported during follow-up of 41 patients managed medically for an average of 36 months before the introduction of ACE inhibitors identified a loss of renal length in 35%, while a significant rise in serum creatinine developed in only 8/41 (19.5%). This conclusion is consistent with long-term studies from Europe in which incidental renal artery lesions were rarely associated with progressive renal failure over more than 9 years of follow-up. These data support the observation that renal artery lesions remain stable in some patients over many years without adverse clinical effects or evident progression, as observed in treatment trials including ASTRAL and CORAL.

It is important that the clinician identify the objectives of evaluating RVD before initiating expensive and sometimes ambiguous investigations. As with all tests, the reliability and value of diagnostic studies depend heavily on the pretest probability of disease ( Box 47.3 and eFig. 47.8 ). It is essential to consider from the outset exactly what is to be achieved. Is the major goal to exclude high-grade renal artery disease? Is it to exclude bilateral (as opposed to unilateral) disease? Is it to identify stenosis and estimate the potential for clinical benefit from renal revascularization? Is it to evaluate the role of RVD in explaining deteriorating renal function? The specific approach to diagnosis will differ depending on which of these is the predominant clinical objective.

Probability of identifying renal artery stenosis based on clinical features.

These data were derived from 477 patients in referral centers for treatment-resistant hypertension (HTN) in the Netherlands. Overall prevalence was 22.4%, illustrating that even in “enriched” patient populations, renovascular disease is not present in the majority. Clinical features allowed selection of patients for testing with a relatively high pretest probability of disease, which affects the validity of testing schemes.

From Krijnen P, van Jaarsveld BC, Steyerberg EW, et al. A clinical prediction rule for renal artery stenosis. Ann Intern Med. 1998;129:705–711.

Identification of ARVD fundamentally requires some form of imaging the renal vasculature. Advances in Doppler ultrasound, radionuclide imaging, magnetic resonance arteriography (MRA), and computed tomography (CT) angiography continue to improve renovascular imaging. The details of these methods are discussed further in Chapter 24 . What follows is a discussion of some of the specific merits and limitations of each modality as they apply to application in renovascular hypertension and ischemic nephropathy ( Table 47.3 ).

Current practice favors limiting invasive arteriography to the occasion of endovascular intervention (e.g., stenting and/or angioplasty). While angiography remains the “gold standard” for evaluation of the renal vasculature, its invasive nature, potential hazards, and cost make it most suitable for those in whom intervention is planned. As a result, most clinicians favor preliminary noninvasive studies. Arterial angiography may be warranted to establish the presence of transstenotic pressure gradients, as recommended in treatment trials. ^,