Thromboembolic Renovascular Disease

C H A P T E R

64

 

Thromboembolic Renovascular Disease Barbara A. Greco, Jamie P. Dwyer, Julia B. Lewis

Renal arterial and venous thromboembolic disease presents as a wide variety of clinical syndromes, ranging from vascular catastrophe with acute renal infarction to progressive decline in renal function due to chronic renal ischemia. Appropriate imaging allows accurate and timely identification of renal infarction, renal artery or venous thrombosis, and other renovascular abnormalities. Thrombotic microangiopathies are discussed in Chapter 28, and renovascular hypertension and atherosclerotic ischemic renal disease are discussed in Chapter 37.

NORMAL ANATOMY Renal Artery The anatomic considerations that affect the clinical outcome of renal arterial thromboembolic events include the size of the vessel involved, from the main renal artery and the branch vessels to the arterioles and glomerular capillaries, and the condition of the collateral blood supply. In most individuals, the kidney has a single artery ranging in diameter from 3 to 7 mm. The incidence of multiple renal arteries is about 30%. Acute occlusion of the renal artery may result in sudden and irreversible renal infarction, particularly if there is a single vessel with inadequate collateral circulation. In the setting of chronic renal artery occlusive disease, such as might exist on a background of atheromatous renovascular disease, the collateral circulation may be more extensively developed. The main collateral vessels to the kidney include the suprarenal, the lumbar, and the ureteral vessel complexes, which can maintain renal parenchymal viability in the face of main renal arterial occlusion. The collateral circulation to the kidney is depicted in Figure 64.1. In a study examining 301 aortograms, the adrenal arteries supplied collateral circulation to the kidney in 60% of cases, the lumbar in 55%, the ureteric in 15%, and the gonadal in 13%.1 The factors determining the development and caliber of these vessels are poorly understood but are likely to relate to individual anatomy, state of the aorta, rate of progression of main renal artery narrowing, and condition of the intrarenal perforating arteries.

Renal Vein Renal veins begin in the subcapsular region of the kidney. These stellate veins communicate with perirenal and cortical venous channels and empty into interlobular veins that drain into arcuate veins. The venae rectae drain the pyramids and join the arcuate veins. Arcuate veins leave the renal parenchyma through interlobar vessels, converging into four to six trunks near the 770

hilum of the kidney (Fig. 64.2). The main renal veins empty into the inferior vena cava; the left renal vein is three times longer than the right (7.5 cm versus 2.5 cm). The left renal vein traverses behind the splenic vein and body of the pancreas before it crosses in front of the aorta near its termination in the inferior vena cava. The left renal vein collects the flow from the left ureteral, gonadal, adrenal, and inferior phrenic veins. In Gerota’s fascia, the perirenal venous network communicates with the retroperitoneal collateral veins from the lumbar, azygos, and tributaries of the portal system.2,3

THROMBOEMBOLIC RENOVASCULAR DISEASE Thromboembolic renovascular disease results in disruption of normal renal blood flow, leading to either renal ischemia or overt infarction. The caliber and type of vessels involved (artery, arteriole, vein) as well as whether one or both kidneys are affected determine the clinical presentation (Fig. 64.3).

THROMBOEMBOLIC ISCHEMIC RENAL DISEASE Ischemic renal disease due to atherosclerotic renovascular disease is discussed in Chapter 37. On occasion, thrombosis of the renal artery or branch vessels occurs acutely and without overt renal infarction, providing a clinical opportunity for renal salvage. The clinical settings in which this might occur include spontaneous thrombosis of atherosclerotic renal artery occlusive disease, spontaneous dissection of the aorta involving the origin of the renal artery, dissection of the renal artery itself, and as a consequence of aortic or renal artery interventions including endovascular stenting. The clinical presentation of renal artery or branch vessel thrombosis without infarction often involves acceleration of hypertension due to renin release, worsening renal function, and even anuria if all of the functioning renal mass is involved. Patients may develop volume overload, pulmonary edema, and symptoms of uremia. The clinical evaluation of the patient includes ruling out overt renal infarction and defining renal parenchymal viability despite main renal or branch vessel thrombosis. This can be achieved by demonstrating a nephrogram on delayed venous-phase imaging by conventional renal arteriography, computed tomographic angiography (CTA) or contrast-enhanced computed tomography (CT), magnetic resonance angiography (MRA) with gadolinium enhancement, or nuclear isotope scintigraphy. The diagnostic approach is complicated in the setting of reduced renal function because of the concern of nephrotoxicity from radiocontrast dye. In addition, the use of gadolinium with MRA is contraindicated if glomerular filtration rate (GFR) is below



CHAPTER

64  Thromboembolic Renovascular Disease

Renal Collateral Blood Supply

771

Renal Vein Anatomy

Intercostal artery Adrenal artery Adrenal vein Gonadal artery Lumbar artery

Lumbar vein Gonadal vein

Ureteral artery

A

Figure 64.1  Renal collateral circulation. Diagrammatic representation of the potential collateral arterial vessels to the kidney.

30 ml/min because of the risk for nephrogenic systemic fibrosis. Treatment involves assessment of the risks versus potential benefits of heroic revascularization procedures. The status of the contralateral kidney and overall residual renal function (RRF) should be weighed against the retrieval of the additional renal function from the ischemic kidney. The ischemic kidney’s length and baseline function before thrombosis determine the potential benefits of renal revascularization. The cardiac and anesthesia risk from the intervention, such as surgical thrombectomy or bypass, has to be considered. Last, the intervention should be delayed until the clinical and renal status of the patient has recovered from any transient insults, such as acute kidney injury (AKI), decompensated pulmonary edema, congestive heart failure (CHF), myocardial infarction, and uremia. Renal function can be salvaged by renal artery surgical revascularization and endovascular stenting in patients with dialysisdependent renal failure due to occlusive renovascular disease.4-6 Predictors of renal recovery are listed in Figure 64.4 and include preserved renal size, evidence of a renal “blush” or nephrogram by imaging, recent loss of GFR, and recent baseline creatinine concentration below 3 mg/dl.7 Figure 64.5 shows thrombosis of a renal artery within a stent placed 1.5 years previously for atherosclerotic renal artery stenosis in a patient with a single functioning kidney. The patient presented with anuric AKI. Percutaneous thrombolytic therapy and renal artery angioplasty restored renal perfusion and renal function.

RENAL INFARCTION When abrupt interruption of renal blood flow occurs without adequate collateral blood supply, renal infarction occurs. Renal infarction may involve the entire kidney or small areas of the cortex or medulla. Both arterial and venous thrombosis and renal

Renal artery and vein

Renal pelvis

B Figure 64.2  Renal vein anatomy. A, There is extensive communication between the renal venous plexus and lumbar, gonadal, and adrenal veins, which provide alternative outflow in the setting of renal vein thrombosis, particularly on the left. B, Transverse section of the kidney showing relative position of vascular structures in the renal pelvis. (From reference 8.)

Clinical Syndromes Associated with Renal Thromboembolic Disease Renovascular hypertension (see also Chapter 37) Ischemic renal disease (see also Chapter 37) Renal infarction Atheroembolic renovascular disease Renal vein thrombosis Transplant renovascular stenosis and thrombosis Figure 64.3  Clinical syndromes associated with renal thromboembolic disease.

772

SECTION

XI  Tubulointerstitial and Vascular Diseases

Predictors of Recovery of Renal Function in Renal Artery Occlusion Preserved renal size (>7–8 cm) Recent baseline serum creatinine < 3 mg/dl (284 µmol/l) Recent rapid loss of GFR Nephrogram visible on delayed or venous phase imaging Distal reconstitution of occluded renal artery Figure 64.4  Predictors of recovery of renal function in renal artery occlusion. GFR, glomerular filtration rate.

artery embolism can cause renal infarction. Unlike thrombotic occlusion of a long-standing stenosis, acute vascular occlusion is often symptomatic. The most common presenting signs and symptoms include loin, flank, or abdominal pain; microscopic hematuria; and transient proteinuria (Fig. 64.6). Transient or accelerated hypertension may occur secondary to abrupt release of renin from the infarcted segment. Some cases may be asymptomatic but are noted as enhancing or functional defects on renal imaging. When bilateral occlusion of both kidney arteries or infarction of a single functioning kidney occurs, the patient presents with oliguric or anuric AKI. AKI is not uncommon, even when infarction is due to renal embolism rather than arterial thrombosis. Systemic signs of renal infarction include leukocytosis, fever, and elevations of lactate dehydrogenase, transaminases, creatine kinase, and alkaline phosphatase.9

Diagnosis A high clinical suspicion is required for diagnosis. CT with the intravenous administration of contrast material is the imaging modality of choice and delineates those areas of the renal cortex that are not perfused. Other potential imaging techniques include MRA (with gadolinium if GFR remains above 30 ml/min or as time-of-flight or phase-contrast imaging) and nuclear renal scan with dimercaptosuccinic acid (DMSA). When the entire kidney is underperfused, it is often difficult to determine whether there may be salvageable renal parenchyma. Studies in experimental animals with acute renal artery occlusion have shown that the collateral circulation can maintain renal viability for up to 3 hours after occlusion.10 In patients with underlying atherosclerotic renovascular disease, collateral vessels may be better developed and renal viability may be maintained for days to weeks. In these subjects, urgent arteriography to identify the location of the arterial thrombosis or embolus may allow percutaneous or surgical revascularization.

Etiology The most common causes of renal infarction are trauma, renal artery embolism, and iatrogenic complications of endovascular procedures (Fig. 64.7). Spontaneous renal artery thrombosis is most often associated with atherosclerotic disease of the aortic or renal arteries, but other vascular anomalies include fibromuscular dysplasia, Marfan syndrome, and Ehlers-Danlos syndrome with associated dissection or aneurysms. Less common causes of infarction include hypercoagulable states, most commonly nephrotic and antiphospholipid syndromes; inflammatory diseases of the retroperitoneum or aortorenal vasculature; and thrombotic microangiopathies (TMAs).

A

B

C Figure 64.5  A, Thrombosis of renal artery within a previously placed stent. After tissue plasminogen activator thrombolytic infusion, recanalization allowed passage of a guide wire. B, Percutaneous renal artery balloon angioplasty of in-stent stenosis. C, Reperfusion of renal artery and kidney after percutaneous transluminal renal angioplasty.

Thrombosis due to Trauma Traumatic injuries to the renal arteries make up 1% to 4% of all nonpenetrating abdominal trauma. Classically, kidney trauma results from a deceleration injury, such as a fall from a great height with an upright landing on impact. This results in stretching of the renal arteries as the kidneys continue downward after the rest of the body has stopped. The subsequent stretching and recoiling of the renal arteries can result in acute thrombosis,



CHAPTER

Signs and Symptoms of Renal Infarction Abdominal or flank pain Leukocytosis Fever Hematuria Elevations of serum LDH, transaminases, CK Acceleration of preexisting hypertension or new onset hypertension AKI Incidental finding of perfusion defects on enhanced renal imaging Figure 64.6  Signs and symptoms of renal infarction. AKI, acute kidney injury; CK, creatine kinase; LDH, lactate dehydrogenase.

which is typically bilateral. Direct blunt trauma to the loin or flank regions associated with motor vehicle crashes, street fights, and sports injuries can also result in renal artery thrombosis. Evidence of lumbar vertebral injury should raise suspicion in the emergency department for renovascular trauma. Even when it is diagnosed early, the success rate for renal revascularization after trauma to the renal vessels remains low, between 0% and 29%.11 Injuries to the renal pedicle that result in diminished perfusion to a single functioning kidney or to both kidneys require rapid intervention, and endovascular stabilization of renal blood flow may be helpful as a bridge to more definitive renal revascularization. Thrombosis due to Hypercoagulable Disorders Clotting disorders, such as protein C or protein S deficiency, antithrombin III deficiency, and rarely factor V Leiden mutations, can predispose to renal arterial thrombosis and infarction in addition to their association with renal vein thrombosis. Hypovolemia, polycythemia, and the use of oral contraceptive agents can increase the risk of thrombosis when these underlying disorders are present. Antiphospholipid antibody syndrome is associated with both arterial and venous thrombotic events and can involve the renal circulation at any level. In patients younger than 50 years, the antiphospholipid syndrome can account for 15% to 20% of all deep venous thromboses and 30% of strokes. It is the most common cause of spontaneous arterial thrombosis. In one report of 16 cases of renal involvement with this syndrome, 15 of 16 subjects had either arterial or venous thrombosis, 10 had intrarenal microangiopathy, one had suprarenal aortic occlusion, and one had main renal artery thrombosis.12 Concomitant thromboses in the mesenteric and cerebral circulation have been reported.13 Renal Artery Embolism The kidneys are frequently the target for emboli from thrombus originating in the heart. In one series, 1.4% of the general population had renal artery embolism at autopsy, of which only 2 of 205 cases (1%) were diagnosed clinically.14 The prevalences of left and right renal emboli are equal, and 12% of cases are bilateral.15 Atrial fibrillation, cardiac thrombus after myocardial infarction, atrial myxoma or other cardiac tumors, endocarditis, paradoxical emboli, and aortic thrombus represent most of the conditions associated with renal embolism. Atrial fibrillation is

64  Thromboembolic Renovascular Disease

773

Causes of Renal Infarction Thrombosis: spontaneous Atherosclerotic disease of aorta and renal artery Fibromuscular dysplasia of renal artery Aneurysms of aorta or renal artery Dissection of aorta or renal artery Marfan syndrome Ehlers-Danlos syndrome Vasculitis involving renal artery Polyarteritis nodosa Takayasu’s arteritis Kawasaki disease Thromboangiitis obliterans Other necrotizing vasculitides Inflammatory disease of the aorta or renal artery Syphilis Tuberculosis Mycoses Hypercoagulable states Nephrotic syndrome Antiphospholipid syndrome Antithrombin III deficiency Homocystinuria Thrombotic microangiopathies Hemolytic-uremic syndrome Thrombotic thrombocytopenic purpura Antiphospholipid syndrome Malignant hypertension Scleroderma Sickle cell nephropathy Polycythemia vera Postpartum hemolytic-uremic syndrome Hyperacute vascular allograft rejection Thrombosis: induced Traumatic Following endovascular intervention Post renal transplantation Embolism Cardiac source Atrial fibrillation or other arrhythmias Native and prosthetic valvular heart disease Infective endocarditis Marantic endocarditis Myocardial infarction with mural thrombi Left atrial myxoma or other tumor Noncardiac sources Atheromatous embolic disease Paradoxical emboli Fat emboli Tumor emboli Therapeutic renal embolization Segmental renal infarction of childhood Cisplatinum and gemcitabine Sickle cell disease or sickle cell trait Figure 64.7  Causes of renal infarction.

the most common cause, with a rate of embolism four times higher than that of the general population; the highest risk is during the first year after the diagnosis of atrial fibrillation, when anticoagulation is subtherapeutic. When echocardiography is undertaken, cardiac thrombus is only rarely detected. Other causes of renal emboli include fiber or foam related to cardiac bypass procedures, calcium from valve annuli, and even “bullet emboli” in the setting of trauma. Aortic endovascular stenting has been associated with a 10% incidence of new renal infarcts, presumably of embolic etiology.16 Paradoxical renal artery embolism may occur in patients with right-to-left cardiac shunts. The most common cardiac shunt is

774

SECTION

XI  Tubulointerstitial and Vascular Diseases

due to atrial septal defects, which are present in up to 9% to 35% of the general population. The diagnosis of paradoxical embolism requires clinical, angiographic, or pathologic evidence of systemic embolism and the presence of venous thrombus along with an abnormal communication between the right and left circulations and a favorable pressure gradient (typically diagnosed by “bubble” echocardiography) for the passage of clot from the right to the left side of the heart. The clinical presentations of renal artery embolism mirror those of renal infarction (Fig. 64.8).15 Pain is present in more than 90% of cases confirmed by radiologic imaging techniques. It is unclear from the literature how many go undiagnosed because of lack of clinical symptoms. There is a 30-day mortality rate of 10% to 13% among patients experiencing renal embolism in the setting of atrial fibrillation.17 Up to 40% of cases have at least transient reduction in renal function. Whereas angiography is the gold standard for diagnosis of renal artery embolism, nuclear isotope scanning is also very sensitive (97%). Contrast-enhanced CT detects 80% of renal embolic events.15 In other reports, CT or CTA has a sensitivity nearly matching that of renal angiography. Aortic and Renal Artery Dissection Aortic dissection can involve the origin of either renal artery, with the false lumen occluding the vessel and impairing renal perfusion. In this setting, the predictors of renal salvage are the same as those for occlusion due to atherosclerotic renal artery stenosis and include preserved renal size, collateral circulation permitting renal viability, and blush on imaging studies. In one report, despite renal atrophy, aortic stent graft placement allowed renal reperfusion and restoration of renal size and function.18 Aortic dissection occurs most commonly in association with atheromatous aneurysmal vascular disease of the thoracic aorta, but it can occur in collagen disorders, such as Ehlers-Danlos type IV or Marfan syndrome, and with arteritis, such as Takayasu disease. Dissection of the renal artery can occur after percutaneous renal angioplasty or stenting (Fig. 64.9), spontaneously with atherosclerotic renovascular disease (ASRVD) or fibromuscular dysplasia of the renal artery, or as a complication of renal artery aneurysms. Risk factors for dissection include age, hypertension, connective tissue disorders, pregnancy, bicuspid aortic valve, and coarctation of the aorta. A high index of suspicion and rapid imaging are critical to improve chances of patient and renal survival. Although MRA is nearly 100% sensitive for diagnosis of aortic dissection, CTA has a sensitivity of 93% and is more readily available, has a more rapid turnaround time, is less dependent on patient factors, and is usually the imaging modality of choice. Middle Aortic Syndrome A rare entity, middle aortic syndrome is a diffuse narrowing of the aorta, considered a form of coarctation, causing renovascular hypertension (Fig. 64.10). The cause is unknown, but associations with fibromuscular dysplasia, congenital anomalies, neurofibromatosis, Williams syndrome, and Takayasu arteritis have been reported. It can present as aortic thrombosis involving the renal arteries. Repair of middle aortic syndrome before thrombosis is the goal, with angioplasty, surgical repair or autotransplantation of ischemic organs. Thromboembolic Complication of Endovascular Interventions Renal artery thrombosis, dissection, laceration, or embolism can occur secondary to vascular interventions, especially those

Clinical Presentation of Renal Embolism Renal Embolism

Atheroembolic Renal Disease

Clinical Signs and Symptoms Flank/Ioin pain (91%) Flank/abdominal/back pain NR Fever (49%) Fever (common) Nausea or vomiting (40%) Malaise/failure to thrive (common) Oliguria (16%) Nonoligruia (common) Transient hypertension NR Labile hypertension NR Skin manifestations 60% Livedo reticularis Blue toes Laboratory Abormalities Elevated creatinine (53%) Elevated creatinine (100%) Elevated LDH (91%) Elevated ESR (97%) Elevated CPK NR Elevated CPK or LDH 38–60% Leukocytosis (85%) Leukocytosis (57%) Elevated transaminases NR Elevated amylase (57%) Hematuria (72%) Eosinophilia (57%) Eosinophiluria (NR) Hematuria/transient proteinuria (NR) Bland sediment (common) Hypocomplementemia 25–70% Diagnostic Testing Contrast enhanced CT or MR Tissue biopsy: Skin, muscle Nuclear imaging/DMSA kidney Renal angiogram Figure 64.8  Clinical presentation of renal embolic disease. CK, creatine kinase; CT, computed tomography; DMSA, dimercaptosuccinic acid; LDH, lactate dehydrogenase; MR, magnetic resonance. (Modified with permission from reference 15.)

Figure 64.9  Cross section of a renal artery with dissection after renal angioplasty. Shown is the dissection with thrombus filling the false lumen. The kidney could not be salvaged.

involving placement of endovascular stents.19 Occlusion of the vessel within the stent can occur many months to years after stent placement, particularly when in-stent restenosis is present. During the past decade, endovascular aortic stents have been used to treat infrarenal abdominal aortic aneurysms. When the stent crosses the orifice of the renal artery, renal perfusion is impaired, and there is a significant risk for renal artery thrombosis.20 Renal artery stent placement may cause intimal



CHAPTER

64  Thromboembolic Renovascular Disease

775

Figure 64.10  Middle aortic syndrome. Angiogram showing typical smooth narrowing of the aorta. There is bilateral stenosis of paired renal arteries. (From reference 21.)

dissection and thrombosis of the renal artery and even aortic dissection. Stent fracture or kinking can be associated with thrombosis of the lumen. Figure 64.11 demonstrates compression of a proximal renal artery stent with associated thrombotic occlusion of the vessel. Careful studies using filters to capture embolic material confirm that renal artery angioplasty with stenting of atherosclerotic renal arteries releases thousands of particles of various sizes in 70% to 100% of cases.22 Preprocedure treatment with antiplatelet agents and intraprocedural use of embolic protection devices during renal stent implantation are under investigation as a means of reducing the frequency of this underdiagnosed cause of renal infarction.23,24 Renal Artery Aneurysms Renal artery aneurysms are rare and associated most commonly with atheromatous, fibromuscular, and vasculitic disease (Fig. 64.12). They are manifested clinically as renovascular hypertension, which is the presenting feature in 55% to 75% of cases. Thrombosis within an aneurysm can lead to distal thrombotic emboli and renal infarcts. Aneurysms with diameters of more than 1.5 cm have a higher risk of rupture. Elective repair of large renal aneurysms should be considered in women of childbearing age because of the risk of rupture during the third trimester of pregnancy and in patients with renovascular hypertension. Other complications of renal artery aneurysms include vessel dissection and arteriovenous fistula formation. Rare Causes of Renal Infarction Rare causes of renal infarction include autoimmune diseases, such as Behçet’s syndrome, systemic lupus, and other autoimmune diseases; Henoch-Schönlein purpura (HSP); chronic Chagas’ disease; and drug abuse, such as intravenous injection or nasal insufflation of cocaine or even smoking marijuana. The exact mechanism involved in the pathogenesis of renal infarction in some of these conditions is unclear.

Treatment of Acute Renal Vascular Catastrophe In the setting of renal infarction, a search for the cause of the renal vascular compromise should be undertaken to determine whether it is embolic or thrombotic. Treatment of the infarction itself is usually conservative and includes pain control and treatment of sometimes labile hypertension. If renal artery occlusion is due to thrombosis associated with hypercoagulable state or embolism from a central source, systemic anticoagulation is indicated. Salvage of the kidney by acute thrombolytic therapy

Figure 64.11  Thrombosis of renal artery complicating renal artery stenting. Right and left renal artery stents note the left renal stent (arrow) is triangular shaped indicating crimping of the proximal portion, which in this case, was associated with thrombosis of the renal artery seen here as no contrast entering the vessel. The right renal stent is patent.

Figure 64.12  Renal artery aneurysm. Angiogram showing large renal artery aneurysm. The aneurysm is patent but is a risk factor for renal artery thrombosis.

has also been attempted with limited success. There is no evidence that thrombolytic therapy can limit infarct size if it is administered in the acute setting. When embolism from a central source results in renal infarction or renal artery occlusion, a search for the source should include evaluation for atrial fibrillation, cardiac mural or atrial thrombus and mass, and valvular lesions. Except in the situation of septic emboli, anticoagulation is indicated to prevent recurrent embolic events. Traumatic renal vascular occlusion leads to renal infarction within 3 to 6 hours. Attempts at renal salvage under these circumstances are often unsuccessful unless the diagnosis is made immediately on presentation of the patient and emergent renal revascularization surgery is feasible clinically. Thrombosis of atherosclerotic renal arteries, because of prior collateral development in most cases, often results in marked

776

SECTION

XI  Tubulointerstitial and Vascular Diseases

ischemia but not infarction of the kidney and allows consideration of optimal surgical and sometimes percutaneous endovascular revascularization to restore renal function.

ATHEROEMBOLIC RENAL DISEASE Atheroembolic renal disease is common and may account for up to 10% of unexplained renal failure in the elderly. It most commonly occurs after arterial manipulation in arteriography, vascular surgery, angioplasty, and stent placement. In patients with extensive atherosclerosis with unstable plaques, spontaneous atheroemboli may occur, especially after the administration of oral or intravenous anticoagulants or thrombolytic agents. The incidence of atheroembolic disease after vascular interventions is unclear, but recent data suggest that it is common.25 A study evaluated the frequency of renal perfusion defects in patients after endovascular stent repair of abdominal aortic aneurysms; 18% of the cases had identifiable renal perfusion defects, and the occurrence of these infarcts was significantly associated with atherosclerotic burden.26 Atheroembolism may therefore be expected to occur in up to 30% of patients with extensive aortic atherosclerosis after endovascular intervention. Ipsilateral renal artery stenosis may be present in up to 80% of patients with renal cholesterol embolization. Conversely, cholesterol emboli were found in the kidneys of 36% of the cases undergoing surgical revascularization.27 Thus, cholesterol embolization may contribute to the loss of renal function in patients with atherosclerotic ischemic renal disease. Most patients are older than 50 years with generalized atherosclerosis and have a history of recent endovascular procedures or signs or symptoms of atherosclerotic vascular disease, such as claudication, abdominal pain, angina, myocardial infarction, transient ischemic attacks, retinal artery emboli, amaurosis fugax, stroke, abdominal aortic aneurysm, renovascular hypertension, or ischemic renal disease. Many have a history of risk factors for atherosclerosis, including hypertension, hypercholesterolemia, diabetes, and smoking.

Figure 64.13  Livedo reticularis. The mottled skin changes associated with peripheral cholesterol embolization may be seen over the legs, buttocks, back, or flank and may be transient.

Clinical Presentation Acute or subacute renal insufficiency due to renal microinfarctions developing as long as six months following the atheroembolic insult is the most common presentation leading to the diagnosis of cholesterol embolization. The clinical picture is multisystemic in nature and involves the kidneys in about 75% of patients. At autopsy, renal involvement is observed in 92% to 100%. If a large shower of atheroemboli causes significant tubular damage, the AKI may have an oliguric phase characterized by a high fractional excretion of sodium. More often, the renal failure is nonoliguric and progressive because of ongoing embolization from a nidus of unstable ulcerative plaque. Some patients have only a moderate impairment in renal function, and others progress to end-stage renal disease (ESRD). Atheroembolic renal disease can also present as a more slowly progressive, often stairstepping subacute renal insufficiency. Urinalysis findings are nonspecific but may include mild proteinuria, microhematuria, pyuria, and eosinophiluria. Renin release by ischemic zones in areas of embolization can lead to labile hypertension early in the course, sometimes associated with transient marked proteinuria. Fever, often low grade, is characteristic. Although the kidneys are the organs most commonly involved, extrarenal cholesterol embolization will provide clues for

Figure 64.14  Hollenhorst bodies. Cholesterol embolus of a retinal arteriole (arrow). (Courtesy Richard Mills, University of Washington, Seattle, Washington, USA.)

diagnosis. Cutaneous findings in up to 60% of patients at initial presentation include blue or purple toes, mottled skin or livedo reticularis, petechiae, and purpura or necrotic ulceration in areas of skin embolization, such as the lower back, buttocks, lower abdomen, legs, feet, or digits (Fig. 64.13). Other organs often involved include spleen (in 55% of cases), pancreas (52%), gastrointestinal tract (31%), liver (17%), and brain (14%). This involvement can result in a number of clinical symptoms, including abdominal or muscle pain, nausea, vomiting, ileus, gastrointestinal bleeding, ischemic bowel, hepatitis, angina, and neurologic deficits. When retinal cholesterol embolization occurs, refractile yellow deposits known as Hollenhorst plaques may be seen at the bifurcation of retinal vessels on funduscopic examination (Fig. 64.14).



Diagnosis The diagnosis of atheroembolic renal disease is suspected when subacute renal failure develops after a vascular intervention in the presence of livedo reticularis. Myriad laboratory abnormalities indicative of tissue injury are associated with cholesterol embolization, including elevated sedimentation rate (in 97% of cases), elevated serum amylase (60%), leukocytosis (57%), anemia (46%), hypocomplementemia (25% to 70%), and elevated lactate dehydrogenase and creatine kinase (38% to 60%). Eosinophilia, which may be transient, is seen in up to 57% of patients. The presence of eosinophilia should raise suspicion for atheroembolic renal disease in the appropriate clinical setting. Serum lactate is usually not elevated unless concomitant ischemic bowel is present. Definitive diagnosis is made by biopsy of an involved organ or system. A skin or muscle biopsy in an involved area may preclude the need for renal biopsy. In most circumstances, the diagnosis is made clinically.

Differential Diagnosis Cholesterol embolization syndrome may mimic vasculitis, occult infection, neoplasm, or thrombotic microangiopathy. Contrast nephropathy with nonoliguric acute tubular necrosis (ATN) may also occur after angiography, angioplasty, or aortic vascular surgical procedures but is often more rapid as opposed to the subacute presentation of atheroemboli. Eosinophilia and eosinophiluria, rash, fever, and renal dysfunction may also be misdiagnosed as acute interstitial nephritis (AIN). Chronic cholesterol embolization syndrome may appear similar to hypertensive nephrosclerosis or ischemic renal disease. In the kidney transplant recipient, renal atheroembolism may mimic acute rejection or chronic allograft nephropathy (CAN).

Pathology and Pathophysiology If clinical or other pathologic evidence has not secured the diagnosis, renal biopsy may be helpful. Diagnosis is based on the presence of birefringent, biconvex, elongated cholesterol crystals or biconcave clefts within the lumina of small vessels left behind in formalin-fixed tissue (Fig. 64.15). Because of the patchy nature of this disorder, open wedge renal biopsy guided by visualization

Figure 64.15  Cholesterol emboli in kidney biopsy specimen. Biconvex cholesterol clefts with giant cell reaction and recanalization of the lumen of a medium-sized renal vessel. (Periodic acid–Schiff stain.) (Courtesy Dr. R. Horn, Vanderbilt University, Hashville, Tennessee, USA.)

CHAPTER

64  Thromboembolic Renovascular Disease

777

of areas of ischemic infarction of the cortex has a higher likelihood of successful diagnosis than does percutaneous needle biopsy. The pathologist should be alerted by the clinician that cholesterol embolization is in the differential diagnosis before the biopsy specimen is processed. In frozen sections of tissue, the cholesterol material can be identified with polarized light microscopy. The pathologic findings may also include intimal thickening and concentric fibrosis of vessels, giant cell reaction to the cholesterol particles, vascular recanalization, endothelial proliferation, tubulointerstitial fibrosis with both eosinophil and mononuclear cell infiltrates, glomerular ischemia, and even focal segmental glomerulosclerosis (FSGS).28 In the kidney, the most commonly affected vessels are the arcuate and interlobular arterioles, leading to patchy ischemic changes distal to these vessels.

Natural History The natural history is determined by the extent of organ involvement and the degree of the embolization. In one series of cases, renal function declined rapidly in 29%, with a more slowly progressive course seen in 79%.29 Among the latter group, the decline in renal function was thought to result from a combination of cholesterol embolization and ischemic renal disease. In another series, the peak serum creatinine concentration occurred within 8 weeks after an angiographic procedure.30 Patients may also manifest acute or subacute renal insufficiency followed by partial recovery of renal function. Conversely, the outcome can be dismal, particularly when cerebral embolization occurs or when there is a large unstable atheromatous burden. Some patients with cholesterol embolization may develop ESRD. These patients have a mortality rate of 35% to 40% during 5 years, even when dialysis is offered.30

Treatment The risk for cholesterol embolization should be considered before angiographic and vascular surgical procedures are undertaken in patients with diffuse, extensive atherosclerotic disease. Because prevention is the most effective management strategy, patients with extensive aortic atherosclerosis should be considered for alternative approaches to cardiac catheterization, such as through the brachial artery. If vascular intervention is performed, signs of embolization should be sought both in the immediate postoperative period and for several months thereafter. When it is feasible, distal embolic protection devices should be used to trap embolic material for removal from the circulation to avoid end-organ damage by embolic debris.31 After the diagnosis of cholesterol embolization is established, further endovascular interventions should be avoided. Poor outcomes have been reported in patients with cholesterol emboli who subsequently undergo coronary artery bypass surgery. When clinical factors dictate the need for aortic, renal, or peripheral arterial surgery, optimal timing and surgical approach are critical. Conversely, there is a growing surgical experience with segmental aortic replacement to remove the source of emboli, particularly when atheroembolic disease occurs spontaneously. Transesophageal echocardiography is often used to identify mobile ulcerative plaque in the aorta to guide intervention. Angiotensin-converting enzyme (ACE) inhibitors are effective in managing the labile hypertension seen early in the course of cholesterol embolization. Corticosteroids have been used with some success in patients with systemic cholesterol embolization and associated inflammatory symptoms.32 There have also been

778

SECTION

XI  Tubulointerstitial and Vascular Diseases

several reports documenting improvement or stabilization of skin signs of cholesterol embolization after administration of statins,33 which should be part of the treatment of the generalized atherosclerosis in these patients. Cholesterol embolization has also occurred after treatment with anticoagulants. Although direct causality between anticoagulants and cholesterol embolization has not been established, the proposed mechanism is that anticoagulants prevent thrombus organization over the ulcerative plaques. Therefore, anticoagulation should be avoided in the acute setting of cholesterol embolization unless a strong lifethreatening indication for anticoagulation is present.

TRANSPLANT RENAL ARTERY STENOSIS AND THROMBOSIS Epidemiology Transplant renal artery stenosis is a common post-transplantation complication occurring most often in the period between 3 months and 2 years after transplantation. The highest reported incidence is 23% in a patient cohort screened angiographically, compared with reported incidences of between 1.3% and 12% when other screening tests are used.34 In many cases, anastomotic stenoses are not hemodynamically significant.34 The use of pediatric kidneys in adult recipients is associated with a higher rate of stenosis because of smaller donor vessel size, leading to greater turbulences and mismatch between donor and recipient vessels. As the transplant population ages, there has been increasing recognition of another subset of patients with pseudo–transplant renal artery stenosis, in which vascular disease proximal to the allograft artery, particularly involving the iliac vessel, results in renal ischemia.

Pathogenesis The pathophysiologic basis for transplant renal artery stenosis is multifactorial and may include atheromatous disease in the donor artery, intimal scarring and hyperplasia in response to trauma to the vessel during harvesting, and anastomotic stenosis, which is most commonly associated with end-to-end anastomoses and may be related to suture technique. In end-to-side anastomoses, stenosis tends to develop in the postanastomotic site, suggesting that turbulence or other hemodynamic factors play a role. Immunologic causes of transplant renal artery stenosis have also been proposed on the basis of histologic similarities with chronic vascular rejection and association with prior acute rejection. Other proposed pathogenic mechanisms include calcineurin inhibitor (CNI) toxicity and cytomegalovirus (CMV) infection.

Clinical Presentation Patients typically present with new-onset hypertension or difficult-to-control blood pressure (BP) with or without graft dysfunction occurring 3 to 24 months after transplantation. Patients may also present with AKI. When the stenosis occurs in the iliac artery above the anastomosis of the transplanted renal artery (pseudo–transplant renal artery stenosis), the patient often presents with ipsilateral lower extremity claudication associated with hypertension and worsening renal function in the allograft.35 Systolic bruits over the transplant are not diagnostic because they may represent turbulent flow in the main vessels in the absence of stenosis or biopsy-related arteriovenous fistulas. Risk factors

for the development of renal artery stenosis include male gender, hyperlipidemia, and elevated serum creatinine at discharge from transplantation.

Diagnosis Renal duplex sonography is the screening test of choice for transplant renal artery stenosis because the vessel is superficial and easy to interrogate. The ratio of velocity in the renal and iliac vessels and the resistive index in the kidney have been shown to predict the hemodynamic response to percutaneous transluminal angioplasty. Phase-contrast MRA has an advantage over arteriography in viewing tortuous renal arteries and may provide information additional to Doppler ultrasound regarding the aorta and iliac vessels. However, with MRA, the surgical clip artifact may obscure the proximal renal artery, and it often cannot resolve peripheral renal vessels. High false-positive rates are associated with sharp anastomotic angles. CTA has the advantage over MRA from an imaging standpoint but requires a large amount of contrast material. The gold standard is selective renal angiography of the transplant and iliac artery. In situations in which the risk for contrast-induced nephrotoxicity is high, carbon dioxide angiography can be performed safely.

Treatment Transplant renal artery stenosis often results in progressive loss of renal function.36 Angioplasty is the preferred initial approach to transplant renal artery stenosis, with initial success rates of up to 75% and patency for follow-up periods of up to 30 months. The average complication rate for angioplasty of the allograft artery is 10%. It is often unsuccessful when there is arterial kinking and is associated with a high complication rate in this setting. The reported rates of late restenosis are between 10% and 33%, necessitating repeated procedures. Although stents are not usually required to treat stenoses within the transplant artery or at the anastomosis, they have been used successfully and are needed routinely to treat the pseudo–transplant renal artery stenosis due to iliac atherosclerotic occlusive disease proximal to the takeoff of the transplant artery.37 Surgical revascularization is reserved for patients in whom angioplasty or stenting has been unsuccessful or complicated. Surgical renal revascularization is difficult and is associated with significant mortality in the transplantation setting. Extensive fibrosis develops around the allograft and often involves the renal vessels, making surgical access risky. Complications include graft loss (in 15% to 30% of cases), ureteral injury (14%), and death (5%).

RENAL VEIN THROMBOSIS Renal vein thrombosis (RVT) is rare and primarily observed in children with severe dehydration (with an incidence in neonates of 0.26% to 0.7%) or in adults with nephrotic syndrome, renal tumors, or hypercoagulable states and after surgery or trauma to the renal vessels.38 When it occurs in adults, the diagnosis is often never considered. Thrombosis of the longer left (7.5 cm) renal vein may also involve the ureteric, gonadal, adrenal, and phrenic branches that drain into the left vein, whereas on the right side, the adrenal and gonadal veins drain directly into the inferior vena cava. The renal veins also communicate with perirenal veins outside of Gerota’s fascia as part of the retroperitoneal collateral venous network: tributaries of the portal system, lumbar, azygos,



and hemiazygos. Because of this network of venous complexes, occlusion of the left renal vein results in enlargement of the systemic collateral vessels and provides some protection against infarction.

Acute Versus Chronic Renal Vein Thrombosis Experimentally, acute RVT is associated with immediate enlargement of the kidney with marked increase in renal vein pressure, leading to a marked decrease in renal arterial flow. Complications include hemorrhagic infarction, kidney rupture, and retroperitoneal hemorrhage. In the dog, the kidney enlarges during the course of 1 week, then proceeds to atrophy as a result of progressive fibrosis. In contrast, slow, progressive (“chronic”) thrombosis may allow collateral formation, resulting in minimal symptoms.

Clinical Presentation Acute RVT is usually symptomatic and associated with loin, testicular, or flank pain; low-grade fever; and in the setting of a single kidney or renal transplant, symptoms of renal failure. Nausea and vomiting often accompany acute RVT, and symptoms might be confused with acute pyelonephritis. Leukocytosis can accompany acute thrombosis. Clinical signs include renal enlargement, which in infants is manifested as a palpable abdominal mass. Hematuria is nearly universal and most often is microscopic. The high venous pressures result in a marked increase in proteinuria. Urinalysis sometimes reveals evidence of proximal tubule dysfunction, such as glycosuria. Oliguric renal failure occurs when RVT results in renal infarction of both kidneys or in subjects with a single kidney. In some cases, RVT is diagnosed only after the patient develops an acute pulmonary embolus and the source of the embolus is investigated or with worsening of renal function in the setting of proteinuric chronic kidney disease (CKD). Chronic RVT may be asymptomatic and is associated with extensive venous collaterals and minimal impairment of renal function and structure. Often, however, microhematuria, increase in proteinuria, and evidence of either reduced GFR or tubular dysfunction are present, particularly when indices of differential renal function are sought, such as with nuclear studies. When RVT causes renal infarction, the distribution of the hypoperfused region tends to be medullary or subcortical. The renal impairment tends to be patchy and subtotal. These patients can develop severe hypertension acutely. The swollen kidney can rupture the capsule and result in massive retroperitoneal hemorrhage.

Etiology The causes of renal vein thrombosis are listed in Figure 64.16. Neonatal Renal Vein Thrombosis RVT occurs in neonates in situations of dehydration and thrombophilia. There is a greater predilection for development of RVT in male infants, with 67% of the reported cases occurring in boys.39 Most cases are unilateral, with the left renal vein more commonly affected. Complications of neonatal RVT may include adrenal hemorrhage, renal atrophy, renal insufficiency, and hypertension. In neonates, the diagnosis is made by Doppler study of the renal veins. Fibrinolytic therapy may be associated with bleeding complications, including adrenal hemorrhage, and

CHAPTER

64  Thromboembolic Renovascular Disease

779

Causes of Renal Vein Thrombosis Malignant neoplasia Direct invasion of tumor into the renal vein Retroperitoneal adenopathy, fibrosis, or tumor compressing the renal vein Extension of inferior vena cava (IVC) obstruction by tumor invasion Hypercoagulable state associated with malignant disease Complication of IVC filters Complication of PICC lines Nephrotic syndrome Membranous nephropathy Lupus nephritis Acute pyelonephritis Complicating inflammatory bowel disease Acute pancreatitis Inflammatory aortic aneurysm Neonatal Congenital Dehydration Thrombophilia Complication of umbilical vein catheterization Transmission of maternal procoagulant factors Hypercoagulable states Antiphospholipid antibody syndrome Factor V Leiden mutation Antithrombin III deficiency Protein S and C abnormalities Hyperhomocysteinemia Elevated levels of clotting factors VIII, IX, and XI Heparin-induced thrombocytopenia Birth control pill Thrombophilia Chuvash polycythemia Post renal transplantation Acute rejection, OKT3 Vascular rejection Compression or kinking of renal vein Hypercoagulable disorders Sticky platelet syndrome Calcineurin inhibitors Viral infection of the allograft Complication of surgical compression After aortic aneurysm surgery After pyeloplasty After partial nephrectomy Traumatic renal vein thrombosis Pregnancy Compression Preeclampsia, eclampsia Complication of embolization of gastric varices Budd-Chiari syndrome Behçet’s disease Figure 64.16  Causes of renal vein thrombosis. PICC, peripherally inserted central catheter.

780

SECTION

XI  Tubulointerstitial and Vascular Diseases

is usually not successful in restoring renal function unless it is undertaken within 24 hours of the thrombotic event.40 Nephrotic Syndrome Patients with nephrotic syndrome have increased risk of venous thromboembolism; deep venous thrombosis is most commonly diagnosed (see Chapter 15).41 The prevalence of RVT in nephrotic syndrome is unclear because it is largely undiagnosed; studies report frequencies between 5% and 62%.38 Numerous abnormalities promoting a prothrombotic state occur secondary to heavy proteinuria. Interestingly, RVT appears more common in membranous nephropathy (MN) and lupus nephritis (LN), but RVT can complicate any cause of proteinuric renal disease. In this setting, RVT can lead to an increase in baseline proteinuria and present with AKI superimposed on chronic renal insufficiency. After Renal Transplantation RVT after transplantation is rare and occurs in less than 0.1% of transplants, usually within the first week after transplantation. It usually leads to graft infarction. Causes include compression of the renal vein, volume depletion, acute rejection, and hemostatic and hypercoagulable states. Factor V Leiden mutation, which occurs in 2% to 5% of the population, is a risk factor for transplant RVT and should be sought when it occurs. Another syndrome known as sticky platelet syndrome can result in posttransplant RVT. There are some data supporting the protective effects of low-dose aspirin in this population. Immunosuppression with cyclosporine and OKT3 may increase the risk of RVT. Unlike the native kidney, the transplant has only a single renal venous outflow, so the consequences of acute RVT are dire, often leading to loss or rupture of the allograft. Renal salvage is possible with early diagnosis and surgical exploration and thrombectomy.42 Pregnancy Pregnancy and the postpartum state are hypercoagulable states. There have been reports of spontaneous RVT in the postpartum period associated with renal infarction. RVT complicating pregnancy should be suspected when clinical clues, such as flank pain and hematuria, are present. Malignant Disease Malignant disease accounts for the greatest number of cases of RVT.43 RVT can result from invasion of tumor of renal origin into the renal vein. About half of renal cell carcinomas are associated with RVT at autopsy. In addition, neoplasia originating in the renal vein or inferior vena cava, such as leiomyosarcoma or cavernous hemangioma, can cause RVT. Extrinsic compression of the renal vein by a tumor or retroperitoneal fibrosis may also cause this syndrome.

Diagnosis Diagnosis of RVT requires imaging. Conventional ultrasound may demonstrate alterations in size and echogenicity. Renal duplex sonography may show increases in resistive indices, and ultrasound can directly visualize the filling defect, but this may depend on the angle of the vein, the body habitus of the patient, and the operator’s experience. In neonates, renal Doppler ultrasound is the diagnostic study of choice. In adults, both CT and magnetic resonance (MR) venography have much greater sensitivity than renal vein duplex studies. CT venography requires a

Figure 64.17  Computed tomography (CT) venogram demonstrating left renal vein thrombosis (arrow). (Courtesy Dr. S. Rankin, Guy’s Hospital, London, United Kingdom.)

significant contrast load, making MR venography preferable in patients with allergy to contrast agents or those at risk for contrast-associated nephrotoxicity. Figure 64.17 is a CT venogram demonstrating unilateral RVT.

Treatment Treatment is controversial and depends on the setting, acuteness, and renal consequences. If there is no contraindication, most patients are treated with systemic anticoagulation acutely. In adults with acute RVT that is compromising renal function, catheter-directed thrombolytic therapy with urokinase or tissue plasminogen activator with or without percutaneous mechanical thrombectomy can be successful in regaining patency of the vessel and restoring renal function.44 There are reports of successful thrombolytic therapy in pregnancy-associated RVT. The long-term benefit of this approach is unclear, and it is less successful when the thrombotic process begins in the small intrarenal venules rather than in the major veins, as is often the case when primary renal disease or a hypercoagulable state initiates the process. In neonatal RVT, which often results in renal nonfunction, thrombolytic therapy and anticoagulation have been used with variable results. In two recent reports of neonatal RVT, supportive care was recommended for unilateral RVT without extension into the inferior vena cava, whereas thrombolytics were used for bilateral cases with impending renal failure. Surgical interventions include nephrectomy, thrombectomy, and retroperitoneal surgery for non–renal-associated abnormalities, such as tumor, retroperitoneal fibrosis, aortic aneurysm, and acute pancreatitis. Surgery tends to be reserved for situations in which the RVT results in hemorrhage from renal capsular rupture or for long-term consequences of RVT, such as hypertension or infection of a nonfunctioning kidney resulting from previous RVT. A conservative approach may be favored when left RVT occurs because of the extensive collateral venous supply on that side, ultimately allowing venous drainage and improvement in renal function. Systemic anticoagulation is indicated acutely to prevent extension of thrombus into the inferior vena cava and for prevention of pulmonary emboli. Anticoagulation should be continued indefinitely in patients with persistent hypercoagulable state after RVT. In addition, eventual recanalization of the



venous system can result in delayed improvement in renal function as measured by nuclear medicine studies.

REFERENCES 1. Yune Hy, Klatte EC. Collateral circulation to an ischemic kidney. Radiology. 1976;119:539-546. 2. Truty MJ, Bower TC. Congenital anomalies of the inferior vena cava and left renal vein: Implications during open abdominal aortic aneurysm reconstruction. Ann Vasc Surg. 2007;21:186-197. 3. Kaneko N, Kobayashi Y, Okada Y. Anatomic variations of the renal vessels pertinent to transperitoneal vascular control in the management of trauma. Surgery. 2008;143:616-622. 4. Hansen KJ, Cherr GS, Craven TE, et al. Management of ischemic nephropathy: Dialysis-free survival after surgical repair. J Vasc Surg. 2000;32:472-482. 5. Siddiqui S, Norbury M, Robertson S, et al. Recovery of renal function after 90 d on dialysis: Implications for transplantation in patients with potentially reversible causes of renal failure. Clin Transplant. 2008;22: 136-140. 6. Thatipelli M, Misra S, Johnson CM, et al. Renal artery stent placement for restoration of renal function in hemodialysis recipients with renal artery stenosis. J Vasc Interv Radiol. 2008;19:1563-1568. 7. Dean RH, Kieffer RW, Smith BM, et al. Renovascular hypertension: Anatomic and renal function changes during drug therapy. Arch Surg. 1981;116:1408-1415. 8. Graham SD, Keane TE, Glenn JF, eds. Glenn’s Urologic Surgery. 7th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health; 2010. 9. Tsai SH, Chu SJ, Chen SJ, et al. Acute renal infarction: A ten-year experience. Int J Clin Pract. 2007;61:62-67. 10. Lohse JR, Shore RM, Belzer FO. Acute renal artery occlusion. Arch Surg. 1982;117:801-804. 11. van der Wal MA, Wisselink W, Rauwerda JA. Traumatic bilateral renal artery thrombosis: Case report and review of the literature. Cardiovasc Surg. 2003;11:27-29. 12. Nochy DE, Daugas E, Droz D, et al. The intrarenal vascular lesions associated with primary antiphospholipid syndrome. J Am Soc Nephrol. 1999;10:506-518. 13. Tektonidou MG. Renal involvement in the antiphospholipid syndrome (APS)—APS nephropathy. Clin Rev Allergy Immunol. 2009;36:131-140. 14. Hoxie HJ, Coggin CB. Renal infarction: Statistical study of two hundred and five cases and detailed report of an unusual case. Arch Intern Med. 1940;65:587-594. 15. Hazanov N, Somin M, Attali M, et al. Acute renal embolism: Forty-four cases of renal infarction in patients with atrial fibrillation. Medicine (Baltimore). 2004;83:92-99. 16. Bockler D, Krauss, M, Mannsmann U, et al. Incidence of renal infarctions after endovascular AAA repair. J Endovasc Ther. 2003;10:1054. 17. Huang CC, Chen WL, Chen JH, et al. Clinical characteristics of renal infarction in an Asian population. Ann Acad Med Singapore. 2008;37: 416-420. 18. Verhoye J, De Latour B, Heautot J. Return of renal function after endovascular treatment of aortic dissection. N Engl J Med. 2005;352: 1824-1825. 19. Gorich J, Kramer S, Tomczak R, et al. Thromboembolic complications after endovascular aortic aneurysm repair. J Endovasc Ther. 2002;9:180. 20. Walsh SR, Boyle JR, Lynch AG, et al. Suprarenal endograft fixation and medium-term renal function: Systematic review and meta-analysis. J Vasc Surg. 2008;47:1364-1370. 21. Panayiotopoulos YP, Tyrrell MB, Koffman G, et al. Mid-aortic syndrome presenting in childhood. Br J Surg. 1996;83:235-240.

CHAPTER

64  Thromboembolic Renovascular Disease

781

22. Edwards MS, Corriere MA, Craven TE, et al. Atheroembolism during percutaneous renal artery revascularization. J Vasc Surg. 2007;46: 55-61. 23. Urbano J, Manzarbetia F, Caramelo C. Cholesterol embolism evaluated by polarized light microscopy after primary renal artery stent placement with filter protection. Vasc Interv Radiol. 2008;19(Pt 1):189-194. 24. Henry M, Henry I, Polydorou A, Hugel MJ. Embolic protection for renal artery stenting. Cardiovasc Surg (Torino). 2008;49:571-589. 25. Polu KR, Wolf M. Needle in a haystack. N Engl J Med. 2006;354: 68-73. 26. Harris JR, Fan CM, Geller SC, et al. Renal perfusion defects after endovascular repair of abdominal aortic aneurysms. J Vasc Interv Radiol. 2003;14:329-333. 27. Krishnamurthi V, Novick AC, Myles JL. Atheroembolic renal disease: Effect on morbidity and survival after revascularization for atherosclerotic renal artery stenosis. J Urol. 1999;161:93-96. 28. Greenberg A, Bastacky SI, Iqbal A, et al. Focal segmental glomerulosclerosis associated with nephrotic syndrome in cholesterol atheroembolism: Clinicopathologic correlations. Am J Kidney Dis. 1997;29: 334-344. 29. Blenfant X, Meyrier A, Jacquot C. Supportive treatment improves survival in multivisceral cholesterol crystal embolism. Am J Kidney Dis. 1999;33:840-850. 30. Scolari F, Ravani P, Pola A, et al. Predictors of renal and patient outcomes in atheroembolic renal disease: A prospective study. J Am Soc Nephrol. 2003;14:1584-1590. 31. Dubel GJ, Murphy TP. Distal embolic protection for renal arterial interventions. Cardiovasc Intervent Radiol. 2008;31:14-22. 32. Graziani G, Sanostasi S, Angelini C, et al. Corticosteroids in cholesterol emboli syndrome. Nephron. 2001;87:371-373. 33. Finch TM, Ryatt KS. Livedo reticularis caused by cholesterol embolization may improve with simvastatin. Br J Dermatol. 2000;143: 1319-1320. 34. Fervenza FC, Lafayette RA, Alfrey EJ, et al. Renal artery stenosis in kidney transplants. Am J Kidney Dis. 1998;31:142-148. 35. Becker BN, Odorico JS, Becker YT, et al. Peripheral vascular disease and renal transplant artery stenosis: A reappraisal of transplant renovascular disease. Clin Transplant. 1999;13:349-355. 36. Deglise-Favre A, Hiesse C, Lantz O, et al. Long-term follow-up of 40 untreated cadaveric kidney transplant renal artery stenoses. Transplant Proc. 1991;23:1342-1343. 37. Bertoni E, Zanazzi M, Rosat A, et al. Efficacy and safety of Palmaz stent insertion in the treatment of renal artery stenosis in kidney transplantation. Transplant Int. 2000;13:S425-S430. 38. Harris R, Ismail N. Extrarenal complications of nephrotic syndrome. Am J Kidney Dis. 1994;23:477-497. 39. Lau KK, Stoffman JM, Williams S, et al. Neonatal renal vein thrombosis: Review of the English language literature between 1992-2006. Pediatrics. 2007;120:e1276-e1284. 40. Messinger Y, Sheaffer JW, Mrozek J, et al. Renal outcomes of neonatal renal venous thrombosis: Review of 28 patients and effectiveness of fibrinolytics and heparin in 10 patients. Pediatrics. 2006;118: e1478-e1484. 41. Kayali F, Najjar R, Aswad F, et al. Venous thromboembolism in patients hospitalized with nephrotic syndrome. Am J Med. 2008;121:226-230. 42. Fathi T, Samhan M, Gawish A, et al. Renal allograft venous thrombosis is salvageable. Transplant Proc. 2007;39:1120-1121. 43. Wysokinski WE, Gosk-Bierska I, Greene EL, et al. Clinical characteristics and long-term follow-up of patients with renal vein thrombosis. Am J Kidney Dis. 2008;51:224-232. 44. Kim HS, Fine DM, Atta MG. Catheter-directed thrombectomy and thrombolysis for acute renal vein thrombosis. J Vasc Interv Radiol. 2006;17:815-822.