CHAPTER 34 Renovascular Hypertension
True/False: Renal artery occlusive disease is the most common form of surgically correctable hypertension.
True. Systemic BP elevations in these patients follow reductions in renal perfusion with activation of the renin-angiotensin system. While this tends to restore renal circulation to normal, it does so in a pathological manner producing systemic hypertension (Greenfield’s Surgery: Scientific Principles and Practice, 2nd ed.).
Renovascular hypertension is caused by hypoperfusion leading to renin release, renin converts angiotensinogen to angiotensin I, which is subsequently converted to angiotensin II by angiotensin-converting enzyme (ACE). List at least 3 physiologic effects of angiotensin II.
1. Direct systemic vasoconstriction.
2. Stimulation of aldosterone secretion resulting in extracellular volume expansion.
3. Preferential glomerular efferent arteriolar vasoconstriction, thus maintaining glomerular filtration despite renal artery hypoperfusion.
4. Recent studies have also revealed additional mechanisms including sympathetic nervous system activation and formation of reactive oxygen species (Garovic and Textor, 2005).
How does the stimulation of aldosterone by the renin–angiotension system contribute to systemic hypertension?
Increased aldosterone levels lead to increased retention of sodium and water. This increased water retention can be compensated for if the patient has unilateral renal artery stenosis (RAS) and a normal second kidney, but the patient will still be hypertensive due to the vasoconstrictive effects of angiotension II. In patients with bilateral RAS, or patients with single kidney and RAS, they are unable to achieve the pressure diuresis required to handle the aldosterone-induced sodium and water retention so they will have volume component to their hypertension.
What percentage of renovascular disease is due to atherosclerosis?
It is estimated that 70% to 90% of renal arterial lesions are due to atherosclerosis, making it the most common form or renovascular disease resulting in hypertension. These lesions more often affect the ostium and proximal third of the renal artery. The adjacent aorta is also affected. Fibromuscular dysplasia frequently involves the distal two-thirds of the main renal artery as well as its branches (Kim et al., 2007).
What is the second most common type of renal artery disease resulting in hypertension and how common is it?
Arterial fibrodysplasia (AF) accounts for up to 25% of renovascular hypertension. AF can be secondary to intimal fibroplasia (which affects children and young adults more than the elderly and makes up 5% of fibrodysplasia cases). AF can be secondary to medial fibroplasias (almost all women and makes up 85% of AF cases). AF can be secondary to perimedial dysplasia (which is also most common in women and makes up 10% of AF cases).
True/False: Pulmonary edema is not a clinical feature of atherosclerotic RAS.
False. Clinical features most suggestive of renovascular hypertension include rapid onset of hypertension after age 50 or development of hypertension in childhood, malignant hypertension or hypertension difficult to manage with 3 or more medications, sudden worsening of mild-to-moderate essential hypertension, and initial diastolic BPs > 115. Additional suggestive clinical findings include peripheral vascular disease, severe retinopathy, azotemia (particularly in patients utilizing an ACE inhibitor or angiotensin II receptor antagonist), hypokalemia, renal atrophy, systolic and diastolic upper abdominal bruits, and pulmonary edema.
True/False: The absence of an abdominal bruit essentially rules out RAS.
False. In patients with angiographically proven RAS, abdominal bruits were audible with a sensitivity range of 39% to 63% and a specificity range of 90% to 99%. Thus, the presence of an abdominal bruit is highly indicative of RAS, but the absence of an abdominal bruit should not rule it out (Kim et al., 2007).
What percentage reduction in renal artery cross-sectional area induces a pressure gradient sufficient to cause increased renin release from the kidneys?
80%. Renin production and release from the kidneys is a complex process wherein renal baroreceptors, acting as stretch receptors, affect the release of renin from juxtaglomerular cells.
Which 2 classes of antihypertensive medications precisely manage renovascular hypertension?
ACE inhibitors and angiotensin II receptor antagonists. Most renovascular hypertension can be managed with these and other antihypertensive medications introduced over the past 2 decades. Previously, less than half of the patients with renovascular hypertension were adequately controlled by medications available at that time. It is arguable whether individuals with well-controlled blood pressure benefit much from revascularization (Garovic and Textor, 2005).
True/False: Renal failure is a side effect of ACE inhibitors.
True. Insofar as ACE inhibitors cause dilation of the glomerular efferent arteriole, there may be a decrease in glomerular filtration rate (GFR). In unilateral RAS, the change in total GFR is usually minimal due to compensatory increase in GFR by the contralateral kidney. However, vascular stenoses that involve both kidneys or a solitary kidney are more likely to be affected by ACE inhibitors resulting in acute renal failure. In 1 study, this occurred in 8 of 136 patients (6%) within 1 month of therapy. Discontinuation of the ACE inhibitor resulted in reversal of the acute renal failure in all, but 1 patient (Garovic and Textor, 2005).
True/False: Endovascular stent placement is more often utilized in the elderly with at least grade 3 chronic kidney disease (QFR 45.5 mL/min/1.73 m2) versus younger patients or those with lesser degrees of chronic kidney disease.
True. In 1 study of 258 patients undergoing endovascular stenting, the mean age was 71 years and 85% of these patients had at least grade 3 chronic renal disease. These patients typically have additional cardiovascular problems and require additional risk-intervention strategies (reduction of cholesterol, discontinuation of smoking, and intensive hypertension control with medications) both before and after revascularization (Garovic and Textor, 2005).
True/False: Restenosis is common following endovascular stenting of the renal arteries when compared with renal artery angioplasty alone.
False. Endovascular stents have greatly improved the patency rates compared with angioplasty alone. Current studies report restenosis following endovascular stent placement as occurring in the range of 12% to 14% (complication rate 7%–9%). Endovascular procedures to restore patency to the renal arteries have increased quite remarkably since the mid-1990s. One reason maybe the number of “drive-by” renal angiographies performed during another catheterization, especially coronary angiography (Garovic and Textor, 2005).
True/False: Randomized controlled prospective studies have clearly demonstrated the benefit of endovascular stents over medication alone.
False. Currently, there is a lack of consensus regarding intervention with endovascular stents. Many nephrologists advocate the use of medication only, whereas interventional subspecialties, especially cardiologists, argue the potential benefits of stent placement. The cardiovascular outcomes in renal atherosclerotic lesions (CORAL) trial is an ongoing NIH-multicenter clinical trial whose enrollment ended in 2010. This trial, like several others before it, including the DRASTIC and the STAR trials, looks at 2 major groups, one treated by medication only, the other with medications and an endovascular stent. Hopefully, through such prospective trials, the true value of endovascular stenting will be determined (Garovic and Textor, 2005).
How often is a clear abdominal bruit heard in RAS?
Forty-six percent of patients.
When does renovascular disease secondary to atherosclerosis most commonly present?
Sixth decade of life. Men are affected twice as often as women. The lesions tend to affect the proximal one-third of the vessel (concentric or eccentric stenosis). 80% of the time, these lesions occur as continuation of diffuse atherosclerosis of the aorta. These lesions are bilateral in 75% of patients in whom they occur. When the lesion is unilateral there is no predilection toward right or left side.
Do nonsteroidal anti-inflammatory drugs (NSAIDs) have any effect on plasma renin levels?
Yes, they cause a decrease.
True/False: Renal accessory arteries are better visualized with Gadolinium-DTPA–enhanced magnetic resonance angiography compared to nonenhanced images.
True. Contrast images allow better visualization of accessory renal arteries. Studies are highly accurate in detecting RAS >50%, with a sensitivity of 93% and specificity of 98%. MRA is particularly useful in patients with impaired renal function who are at increased risk for contrast-induced nephropathy though nephropathy can occur with MRA-associated contrast materials. Additionally, it is important to remember that gadolinium, in approximately 5% of patients with renal insufficiency, has been associated with rare but serious conditions known as nephrogenic systemic fibrosis (NSF) and nephrogenic fibrosing dermopathy (NFD).
Given a group of hypertensive patients on at least 3 antihypertensive medications with a diastolic BP ≥95 mm Hg, what is the prevalence of RAS?
It is 25%. This may be a simple but useful set of criteria to select patients for diagnostic studies. Renovascular hypertension accounts for approximately 5% of all hypertensive patients, yet it is the most common cause of secondary hypertension. Not only can RAS cause hypertension, but it may also lead to progressive renal failure. Modern, less invasive diagnostic techniques, combined with percutaneous transluminal angioplasty and renal stenting, have stimulated a renewed interest in this subject.
True/False: Ischemic nephropathy accounts for >5% of patients with ESRD on dialysis.
True. Seventeen percent of patients are dialysis-dependent because of ischemic nephropathy. Significant RAS has been demonstrated in >50% of patients with a creatinine clearance <50 mL/min. Particularly at risk are patients with DM, hypertension, and generalized atherosclerosis. Median survival of patients on dialysis due to ischemic nephropathy is 27 months versus 56 months for other etiologies.
True/False: Fibromuscular dysplasia rarely progresses to occlusion in cases of renal artery involvement.
True. Nonatheromatous causes of RAS do not commonly progress to occlusion; conversely, 15% of atherosclerotic RAS cases progress to occlusion. The time to occlusion is brief (13 months) in patients presenting with >75% occlusion.
True/False: Atherosclerotic RAS progresses from less than 60% to greater than 60% within 1 year in 30% of patients.
True. The lumen narrows most rapidly from <60% to >60%; 44% of patients progress by 2 years and 48% by 3 years. The progression occurs bilaterally in 20% to 50% of these patients.
In patients undergoing cardiac catheterization, risk factors for RAS include each of the following except which one: extent of CAD, female sex, smoking, or hypertension?
Hypertension. Both multivariate and univariate analysis of patients undergoing cardiac catheterization failed to identify hypertension as a risk factor for significant RAS. Other risk factors that were identified include increasing age, CHF, PVD, and creatinine > 1.06 mg/dL.
True/False: Renal angiography is the gold standard for diagnosing RAS.
True. Although angiography remains the gold standard for identifying RAS, risks include nephrotoxicity and possible complications of arterial puncture (hematoma, cholesterol embolization). Digital subtraction angiography may preclude the need for arterial puncture, but in so doing, requires a larger dose of contrast. CO2 angiography obviates the need for iodinated contrast but is not readily available and is more operator-dependent. Lastly, conventional angiography may miss stenoses en face, requiring oblique imaging to project stenoses (as opposed to CT or MRI).
True/False: A decrease in renal length of > 1 cm is seen in most patients with RAS >60%.
False. Renal dimensional changes of this magnitude are seen in only 26% of such patients. More important is Doppler interrogation of the extrarenal and intrarenal (segmental, interlobar) arteries. Extrarenal Doppler parameters include peak systolic velocity >200 cm/s, renal aortic ratio >3.3 to 3.5, and end-diastolic velocity > 150 cm/s. Intrarenal Doppler parameters include a resistive index <0.45 to 0.59, difference of resistive index with contralateral kidney >0.05 to 0.08, pulsatility index <0.93 (difference of PI with contralateral kidney >0.14), acceleration time >60 to 120 milliseconds, and acceleration >7.4 m/s2.
True/False: Doppler renal sonography is highly accurate in screening for RAS.
True. Five independent studies evaluating 597 patients demonstrated a sensitivity of 89% to 93% and a specificity of 92% to 98%. Positive predictive values of 88% to 98% and negative predictive values of 92% to 98% were reported. The lumbar approach to evaluating the intraparenchymal arteries is unaffected by the number of accessory arteries, bowel gas, or obesity. DRS is operator-dependent and may not yield accurate results regarding multiple renal arteries or branch occlusions. A galactose microbubble-based agent may enhance the Doppler signal but is generally not necessary.
True/False: Spiral CT angiography requires contrast because predictions regarding RAS cannot be made by evaluating renal arterial calcifications.
True. Seventeen percent of patients with no calcification, 30% of patients with <3 mm calcification, and 44% of patients with >3 mm calcification had ≥75% RAS. However, the data do not preclude the use of contrast for accurate diagnostic information. Contrast-enhanced CT studies may visualize vessels as small as 1 mm.
True/False: Captopril challenge tests and renal vein sampling are poor screening tools for ischemic nephropathy.
True. These tests are most useful in differentiating renovascular hypertension from other etiologies. Ischemic nephropathy is often secondary to atherosclerotic RAS. The tests are less sensitive in the situation of bilateral disease and renal compromise.
True/False: Surgical revascularization for ischemic nephropathy virtually always results in substantial improvement in serum creatinine.
False. Fifty-five percent of patients improved (ie, 20% decrease in serum creatinine), 32% of patients revascularized remained stable, 14% of patients worsened, and 6% died perioperatively (accumulated data from 8 studies involving 352 patients from 1983 to 1992).
List 3 preoperative criteria indicative of renal improvement following revascularization for total occlusion of the renal artery.
Any of the following—collateral vessels with nephrogram on angiography, swift preop deterioration of GFR, patent vessels distal-to-proximal occlusion (back bleeding during revascularization surgery), viable nephrons on biopsy, renal length >9 cm, lateralization of renin secretion, and differential urinary concentration on split-function tests. The criteria need to be used together as a guide as individual parameters lack predictive value.
True/False: 30% of renovascular operations for hypertension and renal insufficiency eventually fail.
False. The failure rate is closer to 10%. Postoperative management following revascularization should include routine evaluation of blood pressure, serum creatinine, and periodic noninvasive radiologic assessment of renal blood flow (eg, Doppler renal sonogram, nuclear renography, and MRA). Approximately 10% of patients following revascularization will demonstrate recurrent hypertension or a diminution of renal function. This may be caused by restenosis of the operated vessel, stenosis of the contralateral renal artery, or progressive nephrosclerosis.
Is PTA more successful with atherosclerotic or fibromuscular disease?
Results are better with fibromuscular disease.
What is eplerenone?
It is a selective aldosterone inhibitor used for an antihypertensive. ACE inhibitor medications are still the preferred agents for medical treatment of RAS hypertension.
What about angiotensin receptor blockers?
They appear to be equally effective as ACE inhibitors.
Serum creatinine may increase after therapy with ACE inhibitors. How much of an increase is acceptable?
Usually up to about 35% above baseline.
List the options for open surgical revascularization in patients with renovascular hypertension.
• Aortorenal bypass (infrarenal, end-to-side or end-to-end, using vein or graft)
• Aortorenal artery thromboembolectomy
• Renal artery reimplantation
• Splenorenal bypass
• Hepatorenal bypass
• Aortorenal (supraceliac)
• Iliorenal bypass
True/False: Splenorenal bypass is an ideal operation following a failed left aortorenal bypass.
True. Although this is dependent on the author one reads. The success of the operation depends on the celiac trunk, which is visualized on the lateral aortic film of conventional angiogram, or by less invasive means. It is important to recognize that up to 40% or 50% of patients will exhibit celiac axis stenosis in this patient population. The splenic artery is divided proximally to avoid distal splenic atherosclerosis, and anastomosed end-to-end to the left renal artery. The spleen will remain viable, as collateral blood flow is derived from the gastroepiploic and short gastric vessels.
True/False: Hepatorenal bypass is an ideal operation following a failed right aortorenal bypass.
True. Patency of the celiac axis needs to be ascertained preoperatively for the same reason noted previously. A saphenous vein graft is interpositioned between the common hepatic artery (where it divides into the main hepatic artery and gastroduodenal artery, thus forming a trifurcation) and the renal artery. The proximal anastomosis is performed end-to-side and the hepatic artery is not divided because of ischemic risk to the gallbladder (ischemic risk to the liver is minimal due to portal venous circulation). An end-to-end anastomosis is performed to the kidney to reduce turbulent flow.
True/False: Iliorenal bypass or supraceliac aortorenal bypass are the operations of choice following a failed aortorenal bypass.
False. If the celiac axis is involved by advanced disease or is inaccessible due to prior surgery, the operations above are indicated. Iliorenal bypass is limited by possible progressive disease involving the iliac vessel and requires a long graft (saphenous vein or synthetic) directed cephalad. Supraceliac aortorenal bypass often requires a thoracic as well as an abdominal incision and is much more difficult to tunnel to the right renal artery.
True/False: Renovascular surgery patients are commonly hypertensive in the postoperative period.
True. In the immediate postoperative period, these patients are hypertensive due to hypervolemia, hypothermic vasoconstriction, or pain despite a patent arterial anastomosis. Management is with nitroprusside infusion to maintain the diastolic BP at approximately 90 mm Hg to insure adequate renal perfusion (avoiding graft thrombosis) yet, not so high to prevent anastomotic hemorrhage.
True/False: Risk of hemorrhage following reoperation for renovascular disease is no different than that following the primary operation.
False. Because of dense retroperitoneal fibrosis from the primary operation, hemorrhage is more likely to occur, as embedded lumbar vessels are more difficult to secure and the anastomosis itself is more arduous. Other likely sources of hemorrhage include the ipsilateral adrenal and an untied branch of a saphenous vein graft. Extra-aortic techniques during secondary operations avoid the potential complication of aortic hemorrhage requiring aortic clamping.
Renal artery thrombosis postoperatively following renovascular surgery occurs because of what problems? (List at least 2, try to get all 4.)
Hypotension, hypovolemia, arteriolar nephrosclerosis, or a hypercoagulable state may result in thrombosis. Kidneys with severe nephrosclerosis are best managed by nephrectomy. Technical problems are the most likely cause of postoperative thrombosis (mishandling, kinking, distortion, or angulation of the bypass graft, or atheromatous emboli).
True/False: Secondary revascularization results in cure or improvement in BP in 97% of patients.
True. Approximately 70% of patients will have normalization of their BP following surgical revascularization. Approximately 25% more have reduced hypertension that can be normalized with medical management, leaving less than 5% refractory to surgical revascularization. The operative mortality in 1 series was 1.4% with the incidence of nephrectomy being approximately 40% at reoperation. Nephrectomy will control BP as well as revascularization, and is indicated for the nonsalvageable kidney producing renin.
True/False: Renal arterial bypass grafting (RABG) is more likely to normalize serum creatinine in patients with renovascular hypertension versus percutaneous transluminal renal angioplasty (PTRA) or percutaneous transluminal stent placement (PTSP).
False. Actually all 3 failed to substantially alter creatinine in a study involving 130 patients. In comparing these modalities, the results are as follows:
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