A 61-year-old man with ischemic cardiomyopathy with an ejection fraction of 10% to 15%, revascularized multivessel coronary artery disease, type 2 diabetes mellitus, and a history of smoking presented with recurrent episodes of heart failure exacerbations and pulmonary edema. He was on maximally tolerated medical therapy including aspirin, prasugrel, spironolactone, torsemide, and simvastatin. Prior attempts at initiation of β-blockers and angiotensin-­converting enzyme inhibitors were limited by hypotension. On presentation, the patient had a heart rate of 96 bpm, respiratory rate of 22 breaths/min, blood pressure of 84/68 mm Hg, and jugular venous pulsations to 18 cm H₂O. His cardiac exam showed evidence of a laterally displaced apical impulse with a parasternal heave and an S₃ gallop on auscultation. There were bibasilar rales, and his lower extremities were cool with 3+ pitting edema. Admission labs demonstrated an elevated creatinine of 4.3 mg/dL (baseline 1.0 mg/dL). The patient was placed on inotropic support for cardiogenic shock and ultimately started on continuous venovenous hemofiltration (CVVH) for anuric renal failure. As workup for renal failure, a renal artery ultrasound was performed that showed isoechoic kidneys both approximately 11.0 cm in size without hydronephrosis. Duplex evaluation of the renal arteries was suggestive of bilateral renal artery stenosis >60% (Figure 33-1A). The patient underwent renal artery angiography showing >90% ostial stenosis for both renal arteries (Figure 33-1B). Given the clinical scenario, decision was made to perform renal artery stenting as salvage therapy for anuric renal failure and recurrent heart failure. Postintervention angiogram showed well-expanded bilateral stents with no residual stenosis (Figure 33-1C) and improved renal parenchymal blushing (Figure 33-1D). Within hours of the procedure, the patient started generating urine at a rate of >100 mL/h. His creatinine continued to improve even with cessation of renal replacement therapy (Figure 33-1E). At his 1-year follow-up, the patient continued to have stable New York Heart Association class II symptoms and an outpatient creatinine level of 1.28 mg/dL.

ATHEROSCLEROTIC

• 
  

  Most common etiology of renal artery stenosis (90%)¹

  
  
• 
  

  Affects the proximal one-third of the renal artery

  
  
• 
  

  Present in up to 5% of those with essential hypertension^2,3

  
  
• 
  

  40% prevalence in those with coexisting coronary artery disease^2,3

NONATHEROSCLEROTIC

• 
  

  Fibromuscular dysplasia (FMD; 10%; Figure 33-2)^1,4

  
  
  
  
  • 
    

    Affects the distal two-thirds of the renal artery

    
    
  • 
    

    Typically a disease of young, African American females

    
    
  • 
    

    May be familial

    
    
  • 
    

    Affects the tunica media (85% of the time)¹

    
    
    
    
    • 
      

      Multiple forms; medial fibroplasia accounts for 80% of cases (Table 33-1)⁵

    
    
  • 
    

    Involves extracranial cerebrovascular arteries 25% to 30% of the time⁴

    
    
  • 
    

    Accounts for 5% to 10% of hypertension in those >60 years old

    
    
  • 
    

    “String of pearls” appearance of the renal artery on angiography

    
    
  • 
    

    Complicated by aneurysms and dissections of the affected artery

  
  
• 
  

  Vasculitis

  
  
• 
  

  Embolic phenomenon

  
  
• 
  

  Trauma

  
  
• 
  

  Malignant/cystic compression

  
  
• 
  

  Spasm

UNILATERAL RENAL ARTERY STENOSIS

• 
  

  Renal hypoperfusion stimulates the juxtaglomerular apparatus (JGA) resulting in renin-angiotensin-aldosterone system (RAAS) activation (FIGURE 33-3).⁶

  
  
• 
  

  RAAS activation results in increased sodium and volume retention.

  
  
• 
  

  Angiotensin causes peripheral vasoconstriction.

  
  
• 
  

  The cumulative effect of RAAS activation is to increase the mean systemic arterial pressure and perfusion to the stenotic kidney so as to ensure adequate glomerular filtration rate (GFR).

  
  
• 
  

  This consequently increases filtration through the nonstenotic kidney as well, resulting in a pressure natriuresis and a subsequent normalization of systemic blood pressures.

  
  
• 
  

  This causes hypoperfusion of the stenotic kidney and further stimulation of RAAS.

  
  
• 
  

  Chronic, unilateral stenosis may result in unregulated RAAS activation and, subsequently, dysfunctional RAAS that results in hypertension and volume overload.

  
  
• 
  

  The positive feedback loop in unilateral stenosis can be interrupted by use of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).

BILATERAL RENAL ARTERY STENOSIS

• 
  

  Both kidneys have hypoperfusion, resulting in stimulation of bilateral JGA and activation of RAAS. Neither kidney has the ability to increase filtration given bilateral stenoses, resulting in unchecked fluid retention.^6-8

  
  
• 
  

  Excess sodium, volume, and vasoconstriction result in clinical syndromes of malignant hypertension, angina/coronary ischemia, or pulmonary edema.

  
  
• 
  

  Use of an ACE inhibitor or ARB to block the RAAS mechanism will lead to detrimental impairment in perfusion pressure to the bilateral kidneys, resulting in azotemia.

  
  
• 
  

  Similar effects can be seen in those with a solitary functioning kidney or sole remaining kidney with renal artery stenosis.

ATHEROSCLEROTIC

Atherosclerotic renal artery stenosis (ARAS) should be suspected in those with resistant hypertension or recurrent flash pulmonary edema. Bilateral ARAS typically results in global renal ischemia that causes renal dysfunction and GFR reduction that is visible on laboratory evaluation. Patients with atherosclerotic disease in other vascular beds are at increased risk of ARAS compared to the general population.² Examination typically focuses on the abdomen for a thrill or bruit located above and lateral to the umbilicus, although the absence of such finding does not clinically exclude ARAS.

NONATHEROSCLEROTIC

Non-ARAS is rare but should be evaluated for thorough history and physical exam. The presence of vasculitic conditions should prompt renal artery evaluation in the correct clinical scenario. Trauma to the abdomen may cause laceration or hematoma in the region of the renal artery, resulting in extrinsic compression and stenosis.

Significant and sudden costovertebral pain can be a clue for an embolic phenomenon with resultant renal infarct. Prompt evaluation with computed tomography angiography can be vital for proper diagnosis. Subsequent workup should entail evaluation for thrombotic conditions, atrial fibrillation, valvular lesions, or paradoxical embolus.

FMD represents the second most common cause of renal artery stenosis.⁴ Evaluation of the history may reveal that the patient has a history of FMD in other vascular beds. Thrill and bruit on exam are typically present and affects both renal arteries. FMD should be suspected in cases where there is resistant hypertension; early hypertension; severe/persistent headache; pulsatile tinnitus; transient ischemic attack, stroke, or peripheral arterial disease in those <60 years old; and spontaneous coronary artery dissection. Exam findings are otherwise nonspecific, and a high index of suspicion is necessary to establish the diagnosis.

NONINVASIVE TESTING

Renal Artery Duplex Ultrasound

Use of ultrasound as the initial workup poses minimal risk to the patient. However, image quality can be affected by unfavorable body habitus, presence of bowel gas, and technical expertise. Despite this, with current sonographic technology, there is a 90% success rate in attaining a complete examination.^9,10 Measuring peak systolic velocities (PSV) and end-diastolic velocities (EDV) provides evidence of hemodynamically significant stenosis. The presence of PSV ≥200 cm/s and EDV ≥150 cm/s is suggestive of ≥60% and ≥80% stenosis, respectively. In addition, if velocities are affected due to cardiac dysfunction, a renal–aortic ratio (RAR = PSV_{renal artery}/PSV_aorta) >3.5 indicates the presence of a hemodynamically significant lesion.^9,11 The resistive index [RI = (PSV – EDV)/PSV] is a parameter derived to measure the intra-renal arterial impedance. Those with high indices (>0.8) may have parenchymal dysfunction from causes other than reduced renal arterial blood flow and are unlikely to benefit from ARAS intervention.⁹

Captopril Radionuclide Renography

Captopril radionuclide renography is rarely performed but is used to elucidate the functional and hemodynamic significance of stenotic lesions. An ACE inhibitor is administered and blocks the RAAS, which prevents adequate perfusion of the unilaterally stenotic kidney, thus producing a larger gap between perfusion pressures of the stenotic and normal kidney. In the case of bilateral disease, the use of an ACE inhibitor is likely to produce progressive renal dysfunction for similar reasons but does not allow for any renal augmentation.¹² Ultimately, a renogram (time–activity curve) demonstrating renal uptake and excretion is produced of a predefined compound and compared to the pre–ACE inhibitor curves. This test reportedly provides a 90% sensitivity (50% specificity) for predicting a significant response to revascularization.^13,14

Computed Tomography Angiography

Computed tomography angiography generates a reconstructed vessel evaluation in longitudinal, sagittal, and cross-sectional planes that provides clarity on the location and degree of stenosis. Precontrast images can provide information on concomitant pathology such as renal stones, cysts, or unsuspected masses. The disadvantage of this imaging modality is the lack of hemodynamic evaluation and the use of iodinated contrast, a known nephrotoxin. However, the use of contrast not only highlights the renal arteries, but also allows for evaluation of the aorta, iliac, and femoral systems that provide information for preintervention planning. Sensitivity is 90% to 100% and specificity is 97% to 99% for diagnosis of a luminal stenosis ≥50%.¹⁵

Magnetic Resonance Angiography

Magnetic resonance angiography (MRA) is typically reserved for those with intolerance to iodinated contrast, as the distal renal arteries are incompletely evaluated by MRA. Gadolinium-enhanced gradient-echo MRA has a sensitivity and specificity of 93% to 100% and 90% to 98%, respectively, for diagnosing luminal stenosis ≥50%.^15,16 With only proximal pathology truly elucidated, FMD may be missed. However, an advantage of this modality is the possibility of evaluating hemodynamic significance through various MRA flow-sequencing techniques. Nonetheless, in patients with a priori severe renal dysfunction, gadolinium is a contraindication due to the risk of developing nephrogenic systemic fibrosis.

INVASIVE TESTING

Angiography

Angiography continues to be the gold standard for diagnosis and is primarily advantageous because it allows for concomitant therapeutic interventions. In addition, the invasive nature of the test allows for lesion-specific assessment of hemodynamic significance using fractional flow reserve (FFR; Figure 33-4).^17-19 Again, the risk of iodinated contrast reaction and secondary nephropathy is a concern and should be weighed against the need for definitive diagnosis.