Identification of Renovascular Syndromes

There are five interrelated renovascular syndromes associated with RAS that can be broadly classified as anatomical RAS, renin-dependent hypertension, essential hypertension, reversible renal ischemic dysfunction, and irreversible ischemic nephropathy. These syndromes may occur alone or in combination with each other and with other nonvascular renal diseases. Furthermore, although the type of RAS (FMD, ARAS) is influenced by age, gender, and other patient-related risk factors for atherosclerosis, clinical manifestations (regarding effects on the kidney, heart, and brain) may be similar. Renin-dependent hypertension is much more likely to be caused by FMD in young patients, whereas ARAS in elderly patients is more likely to be associated with essential hypertension. Although both FMD and ARAS can be associated with similar manifestations of injury to the kidneys, heart, and brain (Table 24-2), renal revascularization is more likely to cure hypertension in FMD patients, whereas ARAS patients are likely to require lifelong antihypertensive medical therapy, despite revascularization. The key point is that patients with anatomical RAS without other clinical manifestations may be treated conservatively without revascularization. Prior to revascularization, patients with RAS and other clinical manifestations should undergo assessment of renal perfusion and the extent of parenchymal disease to determine the likelihood of clinical benefit.²

^{Table 24-2} Vital Organ Injury That May Be Caused by Hemodynamically Significant Renal Artery Stenosis

Evaluation of Renal Perfusion

As is true in the coronary circulation, there is poor correlation between angiographic RAS severity and hemodynamic significance, even when quantitative angiography is used.³ As a result, angiography alone is insufficient to establish the presence of renal hypoperfusion, regardless of stenosis severity. Several noninvasive and invasive methods are available to assess the physiological impact of ARAS and identify renal hypoperfusion (Box 24-1; also see Chapter 23). Nuclear scintigraphy and direct glomerular filtration rate (GFR) measurements can assess single- and total-kidney blood flow; diminished renal blood flow ipsilateral to a stenotic renal artery provides reliable evidence of renal hypoperfusion.^4–6 Invasively, renal hypoperfusion can be identified with fractional flow reserve or translesional pressure gradients.^3,7,8

In patients with FMD, angiography alone is nearly useless for assessment of stenosis severity before or after revascularization, or for assessment of renal perfusion. In FMD patients, translesional pressure gradients are extremely useful for localizing the site of critical stenosis and assessing results after intervention (Fig. 24-2). Intravascular ultrasound (IVUS) can also be used to assess intraluminal and vessel dimensions, which are nearly impossible to assess by angiography alone.

Figure 24-2 A 71-year-old female with refractory hypertension was found to have right renal artery stenosis (RAS) by noninvasive imaging.

Selective renal angiography demonstrated fibromuscular dysplasia (FMD) of the right renal artery, but stenosis severity was difficult to assess (A). Intravascular ultrasound (IVUS) revealed complex intraluminal webs (not shown), and the translesional pressure gradient across the diseased segment (black arrows) was 15 mmHg at rest and 20 mmHg after administration of intrarenal dopamine. Angioplasty of the right renal artery (B) did not result in a significant change in appearance by angiography (C) or (IVUS). After initial balloon angioplasty, the hyperemic translesional pressure gradient remained 20 mmHg. A guidewire pullback revealed a pressure gradient limited to a focal segment of FMD at the leading edge (black arrowhead). Repeat angioplasty in the proximal right renal artery did not alter the appearance of the artery by angiography (D), but resulted in complete resolution of the translesional pressure gradient.

Evaluation of Nephropathy

Assessment of baseline parenchymal disease is essential in selecting patients for renal revascularization (Table 24-3), since the presence of parenchymal disease prior to intervention is the most important predictor of adverse outcome. Even if renal hypoperfusion is present, identification of advanced parenchymal disease suggests that renal dysfunction maybe irreversible regardless of revascularization.⁹ The exception is the patient with advanced parenchymal disease, bilateral RAS, and recent dialysis, in whom a small increase in renal blood flow may permit separation from dialysis.^2,10

^{Table 24-3} Clinical Evaluation of Renal Parenchymal Disease

Adapted from Safian RD, Madder RD: Refining the approach to renal artery revascularization. JACC Cardiovasc Interv 2:161–174, 2009.²

Initial clinical evaluation of parenchymal disease includes serum creatinine (Cr), urinalysis for proteinuria, and renal duplex ultrasound to measure renal resistive index (RRI) and kidney dimensions. When evaluating baseline renal function in patients with ARAS, it is important to realize that serum creatinine–based GFR estimates demonstrate good sensitivity but only modest specificity for identifying a measured GFR below 60 mL/min/1.73 m² in individuals with ARAS.¹¹ As a result, additional testing besides serum Cr should be performed to evaluate the presence of underlying nephropathy. Renal resistive index is obtained by averaging values obtained in the upper, middle, and lower intrarenal segmental arteries according to the formula 100 × [1 − (EDV/PSV)], where EDV and PSV are Doppler-derived end-diastolic and peak-systolic velocities, respectively. Compared to patients with RRI less than 80, those with RRI above 80 are older and have more extensive atherosclerosis and worse baseline renal function, consistent with more parenchymal disease. Additionally, baseline RRI greater than 80 is associated with inadequate blood pressure control, worsening Cr clearance, more frequent progression to dialysis, and higher mortality after renal revascularization.⁹ Several factors (renal dimensions, serum creatinine, presence of collaterals, and intact glomeruli by renal biopsy) have been proposed to suggest reversible renal failure, but the predictive value of these factors has not been validated, and renal biopsy is rarely employed for this purpose. Factors that identify irreversible dysfunction include severe diffuse intrarenal arteriopathy, proteinuria greater than 1 g/24 h (especially in a diabetic patient), and marked atrophy of the renal cortex.²

The nephrogram is often overlooked during selective renal arteriography, since many operators tend to focus on the renal artery itself. However, there are several arteriographic features that can indicate the presence of nephropathy, including intrarenal arteriolar narrowing, pruning (cut-off) of interlobar arterioles, and diminished cortical blood flow (Fig. 24-3). It is important to understand that it is best to use all the variables discussed to obtain a “nephropathy profile” because individual variables alone are not sufficiently reliable to assess the degree of nephropathy.²

Figure 24-3 Arteriographic patterns of progressive hypertensive nephropathy.

A, Normal renal arteriogram and nephrogram (left), showing excellent cortical blood flow extending into renal pyramids. In mild hypertensive nephropathy (right), cortical blood flow into renal pyramids is preserved, but there is diffuse intrarenal arteriolar narrowing (AA). B, This is a more advanced stage of hypertensive nephropathy (left) characterized by diminished cortical blood flow, some circulation to renal pyramids (P), and pruning (*) of several lobar arteries. In end-stage hypertensive nephropathy (right), cortical blood flow is absent (CBF), and there is generalized pruning (*) of most lobar vessels.