Abstract
Cardiovascular disease syndromes comprising of coronary artery disease, ischemic stroke, and peripheral arterial disease (PAD) are extremely common in patients with chronic kidney disease (CKD). PAD is particularly common in those with severe CKD, and early detection and effective treatment of PAD is indicated in those with CKD and concomitant PAD. Measurement of the ankle-brachial index is a simple, reliable, and noninvasive test to diagnose PAD that can be used in the office. Lifestyle modification, including exercise and smoking cessation, combined with pharmacologic therapy to manage risk factors have been shown effective in reducing cardiovascular risks in patients with CKD and PAD with judicious use of revascularization strategies to reduce limb loss.
Access provided by Autonomous University of Puebla. Download chapter PDF
Similar content being viewed by others
Keywords
Introduction
Peripheral arterial disease (PAD) is characterized by narrowing (partial or complete) of the peripheral arteries in the limbs, arms, and neck vessels resulting in flow-restrictive stenosis affecting vital organs [1]. PAD is usually not accounted for as a cause of mortality in cardiovascular related deaths, and is often omitted as a relevant cardiovascular end point in most major cardiovascular clinical trials. The lack of adequate clinical data combined with limited awareness of PAD in patients with high cardiovascular disease risk have resulted in increased hospitalizations, limb loss, poor quality of life, and a high cost of treatment [2]. In 2008, a study done in the Medicare population reported total annual expenses of 4.37 billion dollars for PAD-related treatments, most of it from inpatient care [3].
The prevalence of PAD in the USA was at 12.4% as reported by the Atherosclerosis Risk in Communities study (ARIC) (2003–2012) with a year to year variability of 10.3%. A high prevalence was seen in the outpatient setting among women and participants ≥75 years of age. African American women had the highest prevalence rate at 12.8% and African American men had the highest incidence rate of 28.4/1000 participants, with an overall incidence rate of 26.8/1000 among all participants [4].
Atherosclerotic cardiovascular disease comprising of coronary artery disease, ischemic stroke and PAD is extremely common in patients with chronic kidney disease (CKD). CKD, as defined by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI), is based on the presence of kidney damage or glomerular filtration rate (GFR) ≤ 60 ml/min/1.73 m2 [5]. The prevalence of CKD has stabilized at 14% since 2007 after a steady annual rise of 2% since 1988 mainly in stage 3 CKD as reported by United States Renal Data System (USRDS) [6]. Data from National Health and Nutrition Examination Survey (NHANES 1999-2000) reported the incidence of PAD in CKD to be at 24% in patients with stage 3 or greater CKD [7]. With regards to dialysis patients, according to National Kidney Foundation guidelines, all patients with dialysis dependent CKD should be evaluated for PAD, as the incidence of PAD is 15% in all dialysis patients independent of their diabetic status [8]. Table 3.1 summarizes the prevalence of PAD in patients with CKD [9].
Cardiovascular Risk Factors for PAD and CKD
Risk factors for PAD and CKD form a common “soil” for both disease conditions which include advanced age, type 2 diabetes mellitus (T2DM) and smoking, dyslipidemia, and hypertension. In addition to these traditional risk factors for atherosclerotic disease, declining eGFR in itself is an independent cardiovascular disease risk factor with additional pathophysiological mechanisms contributing to the disproportionately increased atherosclerotic burden such as altered bone and mineral metabolism, chronic inflammation, and anemia [10]. The following section briefly reviews these risk factors for PAD, particularly in the context of CKD.
-
A.
Diabetes:
The National Diabetes Statistics Report from 2017 reported the prevalence of pre-diabetes in the overall adult US population to be at 33.9% and at 48.3% in those ≥65 years, with an accounted annual cost of all diabetics related treatments estimated at a whopping $245 billion in 2012 [11]. The over-all cardiovascular disease (CVD) rate in all diabetics was at 70.4/1000 patients and rate of limb amputation was 5/1000 among diabetics while CKD (stage 1–4) was reported in 36.5% in diabetics [12]. Diabetic patients above 50 years also had a higher prevalence (29%) of PAD [13]. The Hoorn Study, conducted in Diabetes mellitus (DM), showed a strong correlation between long-standing DM and PAD, while no associations were seen with impaired glucose tolerance [14]
-
B.
Hypertension (HTN):
Hypertension is one of the primary risk factors for CVD and the second leading cause of CKD [6]. New guidelines set by the American College of Cardiology (ACC) Foundation/American Heart Association have categorized blood pressure as elevated if systolic pressure is between 120 and 129 and diastolic pressure less than 80 mm Hg; Stage 1: Systolic between 130 and 139 or diastolic between 80 and 89 mm Hg; and Stage 2: Systolic at least 140 or diastolic at least 90 mm Hg, thus pushing the prevalence of HTN to 46% nationally [15]. Normal BP is defined as <120/<80 mm Hg. Another study reported by Zhang et al., using data from eight NHANES surveys, found the overall prevalence of HTN was at 31.6% (unadjusted) for the study population and 65.5% when adjusted for +60 years as of 2014 [16]. The annual burden on healthcare for all HTN treatments was approximated to $48.6 billion reported by the Center for Disease Control and Prevention in 2016.
-
C.
Dyslipidemia:
Aggressive lipid-lowering medical treatment has proved effective in lowering death rates and minimizing the risk of developing new atherosclerotic events in patients at high risk for CAD and PAD [17]. Lipid-lowering medication has also specific benefits in PAD patients, as walking performance may be improved [18].
-
D.
Lifestyle factors: smoking and obesity
Cigarette smoking is a major risk factor for PAD. A meta-analysis of 17 studies found a 2.2-fold greater prevalence of symptomatic PAD in smokers compared with nonsmokers [19]. Observational studies showed that obesity is also a major risk factor for peripheral arterial disease (PAD) [20]. Studies have also demonstrated linear relationship between increasing BMI and risk of PAD [21]. Finally, a higher prevalence of PAD might be an indicator of worsening kidney function [22], with a higher mortality rate in patients with decreased kidney function. Hence, it is important if not essential to assess all patients with CKD for PAD in both inpatient and outpatient settings.
In addition, inflammation induced by uremia and chronic oxidative stress seen among patients with CKD plays an important role in PAD and in increasing cardiovascular mortality [23]. Furthermore, elevated levels of phosphate in CKD has vascular toxicity beyond vascular calcification [24].
Impact and Outcomes in Patients of PAD with CKD
PAD (particularly, lower extremity PAD) is more common in patients with CKD. Lower extremity PAD affects around 8.5 million Americans above the age of 40 years [25] and close to 202 million people worldwide [26]. CKD independently increases the risk of developing PAD and is associated with high PAD burden [3]. Patients with CKD and those on dialysis have more below-knee amputations and above-knee amputations than patients with no kidney disease [27]. Patients with advanced PAD have lower survival and higher contralateral amputation rates. Elderly patients on dialysis are at even higher risk of dying or losing the other leg after a major amputation [28]. Amputations have enormous societal and economical cost and impact on quality of life. Table 3.2. depicts PAD outcomes stratified by stages of CKD [29].
Less than half (40%) of the below the knee amputations achieve full mobility and only 1/5th (20%) of the one with the above the knee amputations achieve full mobility [30]. When comparing directly the outcomes of patients with PAD and CKD, those with PAD and CKD had 1.8-fold higher CAD rates, 3.3-fold higher heart failure rates, nearly 2-fold higher amputation rate, more than 2-fold higher in-hospital infections, almost 3 times more acute kidney injury, and almost 2-times the rates of sepsis compared to those without CKD. Patients with CKD and PAD also have a 2.5-fold higher frequency of myocardial infarction, and a nearly 3-fold higher in-hospital mortality rate [31]. CKD patients with PAD have a stepwise increased risk of these adverse outcomes with declining eGFR. The highest in-hospital mortality occurs in patients with CKD stage 4 and Fontaine stage IV PAD [32]. Chronic kidney disease caused 15% higher costs and 21% increased length of stay compared to the PAD cohort without CKD [32]. PAD prevalence rates are significantly higher in patients with ESKD (End Stage Kidney Disease) on maintenance dialysis. When the definition of PAD is inclusive of the clinical criteria including a history of PAD, symptomatic claudication, signs of critical limb ischemia (CLI) or reduced pulses on examination, limb artery revascularization, or past ischemic amputation, PAD prevalence ranges from 23% to 25% among those with ESKD [30, 33]. USRDS 2010 claims data reveals nearly 46% of all dialysis patients in the USA were offered care for PAD [34]. Patients with CKD and concomitant PAD go on to have higher mortality rate than those with PAD without CKD or CKD without PAD. Compared to patients with either CKD or PAD alone (26–28%) or neither condition (18%), the highest 6-year mortality rates were found in patients with both PAD and CKD (45%) [35]. A prospective study of 938 patients with ABI <0.9 reported 38% mortality in patients with PAD and CKD compared with only 5% in those with neither disease at 3 years of follow-up in a Chinese study [36]. In patients with CKD and asymptomatic PAD but abnormal ABIs, the relative risk of 10-year all-cause mortality was shown to be twice as high and cardiac mortality four times as high compared with individuals with normal ABIs in a comparable patient population [37]. The patients with stable PAD with CKD were noted to have higher incidence of acute limb ischemia and acute visceral ischemia. Even the prognosis after acute peripheral vascular events was very poor with significantly high disability and mortality (about 70%) at 1 and (90%) at 5 years [38].
Interventional outcomes are also affected by the presence and stages of CKD. In lower extremity interventions, the presence of CKD increased the likelihood of requiring interventions for multiple vessels. The likelihood of death or amputation at 30 days was increased by three times in the presence of severe CKD [32]. With severe CKD, the need for repeat percutaneous intervention in infrainguinal arteries with previous interventions were also noted to be higher [39]. Higher mortality and decreased amputation-free survival has been noted in individuals undergoing surgical revascularization with lower extremity bypass surgery [40]. However, there is lack of robust data on graft patency rates in this population and in individuals with CKD undergoing surgical repair of abdominal and infrainguinal arterial disease.
There is at present no conclusive data to show decreased patency or increased intervention in patients with CKD undergoing aorto-iliac stenting [41]. However, after open Abdominal Aortic Aneurysm (AAA) repair or Endovascular Aortic Aneurysm repair (EVAR), the risk of complications and cardiovascular events associated were higher based on the severity of CKD as reported in Table 3.3 [29]. The 30-day mortality is twice as high in individuals with severe CKD (6% vs. 3%; p = 0.0081) when compared with milder disease [42, 43]. Also, patients with severe CKD who underwent open repair of AAA had a 30-day mortality rate of 10% and a 40% rate of any complication (Table 3.3) [29, 44].
Patients with carotid artery disease in conjunction with CKD appear to have worse outcomes, similar to other vascular beds (Table 3.4) [29, 45]. In patients undergoing carotid artery stenting (CAS) and carotid endarterectomy (CEA) there were worse outcomes in CKD population. Moderate CKD (GFR 30–60 ml/min/1.73 m2) increased the risk of cardiac events (1.7% vs. 0.9% for controls, p < 0.001) and pulmonary complications (2.1% vs. 1.3% control; p < 0.001) without an increase in mortality. However, severe CKD (GFR less than 30 ml/min/1.73 m2) had a significantly increased mortality (3.1% vs. 1.0% control, p < 0.001) [46]. GFR less than 60 ml/min/1.73 m2 has also been identified as a risk factor for poor 5-year survival in individuals undergoing CEA even for asymptomatic carotid artery disease [47]. Similar trends were seen in patients undergoing CAS. No significant difference in mortality was noted in individuals with moderate CKD (GFR 30–60 ml/min/1.73 m2) compared with those having GFR greater than 60 ml/min/1.73 m2. However, once GFR declines to the range of severe CKD, the 30-day mortality increased roughly 5 times. (0.66% normal renal function, 1.15% moderate renal insufficiency, and 5.45% severe renal insufficiency; p = 0.005) (Table 3.4) [29, 48] .
Awareness of PAD
Study conducted on PAD awareness revealed a disturbing lack of awareness, markedly lower than awareness about stroke, coronary artery disease, or diabetes mellitus [49]. The PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) program, a multicenter, cross-sectional study conducted at 27 sites in 25 cities and 350 primary care practices throughout the USA in June–October 1999, revealed prevalence of PAD in primary care practices is high, yet physician awareness of the PAD diagnosis is relatively low [13].
Clinical Presentation
Extra Cranial Carotid Arterial Disease
CKD is an independent predictor of carotid plaques, carotid artery stenosis, and occlusions in patients with acute stroke [50], with extracranial atherosclerotic disease accounting for up to 15–20% of all ischemic strokes [51]. CKD is associated with an increased risk of both ischemic and hemorrhagic stroke [52]. The effect of CKD on incident stroke differs among regions and races and is greater in Asian than in non-Asian people [53]. CKD seems to be predictive of severe neurological deficits and poor vital and functional outcomes after both ischemic and hemorrhagic strokes, which is partly due to the limitations of pharmacotherapies including limited use and effects of novel oral anticoagulants, other antithrombotic treatments, and reperfusion treatment for hyperacute ischemic stroke [54].
Diagnostic Evaluation
The correlation between severity of vascular stenosis and ischemic events is imperfect, and other characteristics have been explored as potential markers of plaque vulnerability and stroke risk. Among asymptomatic patients with carotid bruit, fewer than half of the stroke events affected the cerebral hemisphere ipsilateral to the bruit and carotid stenosis [55]. Duplex Ultrasound (DUS) is recommended as the first-line imaging in asymptomatic patients with suspected carotid artery stenosis or a carotid bruit as well as in those with transient neurologic symptoms that are suspected to be ischemic. Computed Tomography Angiography (CTA) or Magnetic Resonance Angiography (MRA) are imaging options when DUS is not readily available or when results are equivocal [56]. DUS requires no radiation or intravenous contrast and is relatively inexpensive compared with CTA or MRA. The Society of Radiologists in Ultrasound (SRU) consensus criteria defines critical stenosis (greater than 70%) as a peak systolic velocity greater than 230 cm/s along with an end diastolic velocity greater than 100 cm/s and an internal carotid artery to common carotid artery ratio greater than 4.0 [57]. Peak systolic velocity greater than 125 cm/s but less than the criteria for critical stenosis constitutes 50–69% stenosis. DUS has its own limitations. A very tight stenosis may be inaccurately interpreted as total occlusion on DUS. As total occlusions are not revascularized, an opportunity for therapeutic intervention may be missed. It also can overestimate the degree of stenosis compared with digital subtraction angiography (DSA) [58, 59]. Accuracy of DUS is also somewhat operator dependent [60].
The sensitivity and specificity of DUS when compared with DSA for detecting 70% or greater carotid artery stenosis is in between 85% and 90%. [61,62,63]. CTA provides detailed anatomical imaging from aortic arch to circle of Willis. Although CTA has 100% sensitivity and more than 60% specificity, like DUS, it also can overestimate the degree of stenosis and not be able to differentiate between a total versus sub-total occlusions [64]. CTA involves radiation exposure and use of iodinated contrast, which in patients with CKD could be contraindicated or predispose them to contrast induced acute kidney injury (CI-AKI)
Magnetic resonance angiography (MRA) has similar sensitivity to CTA and higher specificity (sensitivity approaches 100% and specificity of 82–95%) [65,66,67,68,69]. Contrast enhanced MRA is superior to non-contrast enhanced MRA, but advanced CKD poses limitations to the use of contrast enhanced MRA given the high risk of nephrogenic systemic fibrosis with the use of gadolinium in advanced CKD.
Catheter angiography is used for ambiguous or uncertain noninvasive diagnostic studies and planned endovascular interventions. It is the gold standard imaging modality. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) method of measuring the degree of stenosis is probably the most widely accepted and used predominantly in trials. The residual lumen of the stenotic segment is compared with the normal distal ICA [70]. Catheter angiography using digital subtraction angiography can be performed with less contrast compared to CTA and MRA, which is of relevance in CKD patients. Also, artifact from metal implants or calcium deposits is not limiting in terms of visualization. The risk of stroke is less than 1% with experienced operators [71,72,73,74,75,76,77].
Vertebral Artery Disease
The left and right vertebral arteries form the posterior cerebral circulation and terminal segment of the vertebral arteries provides important branches which include the anterior and posterior spinal arteries, the posterior meningeal artery, small medullary branches, and the posterior inferior cerebellar artery. Vertebral artery disease presents as dizziness, vertigo, diplopia, perioral numbness, blurred vision, tinnitus, ataxia, bilateral sensory deficits, and syncope. Vertebral artery disease is the etiology for up to 20% of posterior circulation strokes [78,79,80,81]. Imaging difficulties in regards to visualizing the origins of the vertebral arteries by ultrasound imaging possibly underestimates the incidence of vertebral artery stenosis as etiology of posterior circulation strokes [78]. Eighty two of 407 patients in the New England Medical Center Posterior Circulation Registry with ischemia affecting the posterior circulation were noted to have >50% stenosis of the extracranial vertebral artery [82].
Higher prevalence of more than 50% vertebral and basilar arterial stenosis were noted in posterior circulation TIA or minor stroke patients on contrast-enhanced MRA in comparison to more than 50% carotid stenosis in patients with carotid territory events. Vertebro-basilar arterial stenosis also was associated with higher risk of early recurrent stroke and multiple ischemic episodes [83].
Non-invasive imaging methods were compared with catheter-based angiography for detection of vertebral artery stenosis in a systematic review of 11 studies, which reported that CTA and contrast-enhanced MRA were associated with higher sensitivity (94%) and specificity (95%) compared to DUS (sensitivity 70%, specificity?). CTA had slightly superior accuracy compared to MRA [84]. Both MRA and CTA do not reliably delineate the origins of the vertebral arteries, and catheter-based contrast angiography is indicated before revascularization for patients with symptomatic posterior cerebral ischemia. Digital subtraction arteriography (DSA) with intravenous contrast is sometimes used when selective catheterization of the vertebral arteries cannot be achieved, but the accuracy of this method compared with CTA is not established.
Subclavian Artery Disease
Subclavian and brachiocephalic arterial disease is relatively uncommon and is typically due to atherosclerosis. Takayasu arteritis, giant cell arteritis, fibromuscular dysplasia (FMD), and radiation-induced arteriopathy are other causes. Increased prevalence in CKD patients have not been reported. However, subclavian steal syndrome in the absence of subclavian artery disease in patients with hemodialysis fistulae has been reported [85].
Subclavian steal syndrome is manifested when proximal subclavian artery is stenosed or occluded, resulting in branches distal to the obstruction providing collateral circulation to the arm by flow reversal in the vertebral artery and internal mammary arteries. It is often asymptomatic but at times it can cause arm fatigue. However, if the dominant vertebral artery is affected by subclavian obstruction, reversal of flow in the vertebral artery may reduce basilar artery perfusion and cause posterior cerebrovascular insufficiency. In such cases symptoms are typically aggravated by exercising the ipsilateral arm, which worsens the flow reversal. Similar phenomenon affects the internal mammary artery, when used as a conduit for CABG (Coronary Artery Bypass Grafting) surgery causing angina [86].
DUS may identify reversal of flow in a vertebral artery and CTA or MRA of the aortic arch may identify stenosis of the subclavian artery.
Aorto Iliac and Lower Extremity Arterial Disease
Aorto-Iliac disease and disease of lower extremities predominantly manifest as buttock claudication, claudication of thighs and or calves, vasculogenic erectile dysfunction, tissue loss in form of non-healing ulcers, acute limb ischemia, and critical limb ischemia. Among patients with PAD, majority do not have typical claudication but have other non-joint related limb symptoms or could be asymptomatic [13, 87]. Atypical symptoms could manifest as pain or discomfort which begins at rest, worsens with exertion but does not stop an individual from walking and is not alleviated within 10 min of rest [88]. Detailed lower extremity vascular examination is an important component of the clinical assessment for PAD. Lower extremity pulses should be assessed and rated as 0 for absent, 1 for diminished, 2 for normal, and 3 for bounding [89]. Dorsalis pedis pulse can be absent on clinical examination in a significant percentage of healthy patients. Hence absent dorsalis pedis pulse is less accurate for diagnosis of PAD than absent posterior tibial pulse [89, 90].
ABI (Ankle–Brachial Index) has sensitivities ranging from 68% to 84% and specificities from 84% to 99% in patients with symptoms or signs suggestive of PAD [91,92,93,94,95,96]. Segmental lower extremity blood pressures and Doppler or plethysmographic waveforms (pulse volume recordings) help in localizing anatomic segments of disease in terms of aorto-iliac, femoro-popliteal, or infra-popliteal involvement [97, 98].
TBI (Toe–Brachial Index) is useful to evaluate for PAD in patients with non-compressible arteries which cause an artificial elevation of the ABI [99, 100]. A TBI less than or equal to 0.70 is abnormal and diagnostic of PAD because the digital arteries are rarely non-compressible [100,101,102,104] and useful in those with abnormal ABI due to vascular calcification as seen in CKD and diabetes mellitus [101, 104]. Exercise treadmill ABI testing aids in establishing the diagnosis of lower extremity PAD in the symptomatic patient when resting ABIs are normal or borderline and also to differentiate claudication from pseudo-claudication [105,106,107,108]. TBI with waveforms, transcutaneous oxygen pressure (TcPO2), or skin perfusion pressure (SPP) help in diagnoses of CLI in patients with non-healing wounds or gangrene, when ABI is normal (1.00–1.40) or borderline (0.91–0.99) [109,110,111,112,113]. Correlation between toe–brachial index (TBI), Transcutaneous oxygen tension (TcPO2), and SPP has been reported, SPP ≥ 30–50 mm Hg is associated with increased likelihood of wound healing [97], and TcPO2 >30 mm Hg predicts ulcer healing [114]. DUS, CTA, or MRA is useful in formulating an interventional plan especially with guidance in selection of vascular access sites, identification of significant lesions, and determination of the feasibility of as well as the modality for invasive treatment. Good sensitivity and specificity of DUS, CTA, and MRA when compared with invasive angiography has been reported [114,115,116,117]. CTA and contrast angiography may predispose patient with CKD to CI-AKI and should be considered in decision making.
Acute limb ischemia (ALI) is a medical emergency. It must be recognized rapidly and initial clinical evaluation should focus on rapid assessment of limb viability and potential for salvage. It does not require imaging for diagnosis [118,119,120,121,122]. Clinical assessments in setting of ALI include symptom duration, pain intensity, and motor and sensory deficit severity to determine the category of limb ischemia. The bedside arterial and venous handheld continuous-wave Doppler provides very useful information when clinical examination is usually not reliable or inaccurate for pulse palpation [97]. The loss of arterial signal on Doppler interrogation indicates threatened limb and the absence of both arterial and venous Doppler signal typically indicates limb may be non-salvageable.
Calciphylaxis is a complex disorder of microvascular calcification that is typically seen in patients with ESRD and manifests as painful cutaneous lesions with poor outcomes [123]. The condition is characterized by occlusion of micro-vessels in the subcutaneous adipose tissue and dermis that results in intensely painful, ischemic skin lesions. Currently, there are no approved therapies for Calciphylaxis.
Management of PAD in CKD
Preventative Risk Factor Modification
Although effects of smoking cessation have not been specifically studied among patients with CKD, smoking is associated with an increased risk of amputation among patients with claudication. Cigarette smoking is the major risk factor for incidence and prevalence of PAD. [19, 124]. A meta-analysis of 17 studies found a 2.2-fold greater prevalence of symptomatic PAD in smokers compared with nonsmokers [19].
Compared with those who never smoked, current smokers had strong association with CKD, even after quitting smoking. CKD and PAD prevalence was noted to be higher in subjects with fewer elapsed years since smoking cessation compared with those who quit over 15 years before [125]. Thus, smoking cessation should be strongly encouraged in patients with CKD and PAD given their high risk for PAD events and other cardiovascular events.
Many long-term smokers with PAD are willing to initiate a serious cessation attempt and to engage in an intensive smoking cessation program. Intensive intervention for tobacco dependence is a more effective smoking cessation intervention than minimal care. (AHA/ACCF 2011)
Lipid Lowering Therapy
Lipid lowering therapy is known to reduce risk of cardiovascular death, MI, and stroke based on various well-qualified studies [126]. Cholesterol lowering reduced overall incidence of cardiovascular events among general population and among those with PAD [127]. Thus, statin therapy has been recommended for patients with PAD based on their elevated risk of cardiovascular death, myocardial infarction, and stroke.
The Study of Heart Protection (SHARP) trial supports the efficacy of lipid lowering therapy for reducing cardiovascular mortality and cardiovascular events in patients with CKD compared with placebo. The need for coronary revascularization and risk of atherosclerotic vascular events were lower in the treatment group compared with placebo group in patients with CKD. Although there are smaller trials demonstrating the benefit of statin therapy in PAD patients, specific data from large dedicated randomized trials for PAD are lacking [127, 128]. Systemic inflammation has been shown to worsen the progression of PAD and other atherosclerotic diseases. Statin therapy is known to reduce the systemic inflammation and C-reactive protein (CRP) levels thus possibly additionally benefiting patients with PAD [127, 129].
Hypertension
There is an increased incidence of both CKD and PAD in hypertensives [129,130,131]. Hypertension should be controlled in patients with CKD to reduce morbidity from cardiovascular and cerebrovascular disease and also to delay progression of CKD [131, 132]. Antihypertensive therapy should be administered to patients with hypertension and PAD to reduce the risk of MI, stroke, heart failure, and cardiovascular death [130].
Medical Therapy for PAD
Cilostazol is a phosphodiesterase inhibitor that has both antiplatelet and vasodilating properties, and is indicated for alleviating intermittent claudication. Cilostazol increases pain-free and maximal walking distance among persons with claudication. Beebe et al. showed that after 24 weeks, patients who received cilostazol 100 mg twice a day had a 51% mean improvement in maximal walking distance versus placebo (p < 0.001 add CI) [133, 134]. It has also been showed to increase the primary patency of revascularized vessels, although there were no differences in death and amputation rates [133].
Supervised Exercise Therapy
Exercise training has shown well-established benefit after a typical 12-week supervised exercise training program [135, 136]. Exercise training directly modifies several pathophysiological mechanisms in PAD, including improved skeletal muscle metabolism, endothelial function, and gait biomechanics [137]. Supervised exercise therapy or stent revascularization along with optimal medical therapy has also been shown to be superior to just medical therapy alone at 18 months [138]. Although there are no clinical trials evaluating the exercise therapy for PAD in patients with CKD, it has been well established via single-site studies and a meta-analysis that a 12-week intervention of supervised exercise (SE) improves exercise performance and QOL in PAD [136].
Invasive Therapy
Ideally all patients with chronic kidney disease (CKD) who develop symptoms consistent with critical limb ischemia should receive immediate evaluation and referral to a specialist competent in treating vascular disease. The indications for percutaneous and surgical intervention for intermittent claudication and critical limb ischemia recommended by the 2016 ACC/AHA guidelines are no different for patients with CKD than for the general population. Early intervention is the key in CKD patients. Given the higher rate of arterial calcification in CKD patients, progressive arterial calcium deposition in late stage disease increases the risk of prolonged procedures, higher use of contrast amount and radiation, with possibly further worsening of kidney disease. Further to this calcified arterial disease has been shown to increase risk of amputation in patients with PAD [139].
Invasive Management Strategies in PAD
There continues to be impressive advancement in invasive management strategies for PAD. The Trans-Atlantic Inter Society consensus (TASC) group categorizes aorto-iliac and femoral popliteal lesions into A, B, C, and D based on anatomy and lesion complexity [15]. The TASC classification has been predominantly used as a guideline to dictate surgical versus endovascular intervention in PAD patients. (Figs. 3.1 and 3.2)
TASC classification of aorto-iliac lesions. CIA common iliac artery, EIA external iliac artery, CFA common femoral artery, AAA abdominal aortic aneurysm. (From Norgren et al. [178]. Used with permission from Elsevier)
TASC classification of femoral popliteal lesions. CFA common femoral artery, SFA superficial femoral artery. (From Norgren et al. [178]. Used with permission from Elsevier)
Endovascular Therapies
Endovascular therapies remain the dominant strategy for managing symptomatic PAD refractory to medical therapy but use iodinated contrast. It is key that clinicians use strategies to limit contrast amount to prevent further kidney damage in patients with CKD.
Strategies to Limit Contrast Use
Contrast induced acute kidney injury (CI-AKI) is an acute and potentially severe complication after exposure to intravascular contrast media, particularly for patients with pre-existing CKD. CI-AKI is generally defined as an increase in serum creatinine concentration of 0.5 mg/dL or 25% above baseline within 48 h after contrast administration [140,141,142]. There is no effective therapy once injury has occurred; therefore, prevention is the cornerstone for all patients at risk of acute kidney injury (AKI) [143].
Increasing degrees of renal impairment have been associated with escalating levels of risk for CI-AKI [144]. Among patients in the Minnesota Registry of Interventional Cardiac Procedures, CIN was diagnosed in 22% of patients with serum creatinine >2 mg/dL and in 30% of patients with serum creatinine >3 mg/dL. Diabetes, increased age, higher dose of contrast agent, route of contrast administration (intra-arterial vs. intravenous), congestive heart failure (CHF), hypertension, periprocedural shock, baseline anemia, postprocedural drop in hematocrit, use of nephrotoxins, nonsteroidal anti-inflammatory medications, volume depletion, increased creatine kinase-MB, and need for cardiac surgery after contrast exposure have been associated with increased risk of CI-AKI [144,145,146].
Mehran et al. have published a simple risk score of CIN including both preprocedural and periprocedural risk factors for coronary contrast imaging; to a large extent this data can be extrapolated towards PAD patients undergoing endovascular interventions. Mehran’s model includes CHF, hypotension, intra-aortic balloon pump, age >75 years, anemia, diabetes mellitus, contrast volume, and estimated glomerular filtration rate (eGFR) as predictive factors for the development of CI-AKI [147].
CI-AKI was observed in 8–15% of total patients and 40–50% of high-risk patients depending on the prevalence of risk factors and definition of CI-AKI. The amount of contrast used has been determined to be the most important factor in inducing CI-AKI [140, 141, 148, 149]. Various alternative strategies to contrast use have been invented and evaluated for this purpose. Cigarroa et al. used an empirical formula of 5 ml of contrast material multiplied by body weight (kg) divided by serum creatinine (mg dl−1) to set a contrast volume limit in their study [150]. Gurm et al. reported that a contrast volume restricted to less than thrice and preferably twice the calculated creatinine clearance might be valuable in reducing the risk of CIN [151]. Two main alternative modes of imaging support used during endovascular interventions are ultrasound based IVUS (Intra Vascular Ultrasound) and Carbon Dioxide Angiography (CO2 angiography), which are briefly described below.
CO2 Angiography
In the 1970s, Hawkins pioneered the intra-arterial application of carbon dioxide (CO2) gas angiography for high-risk patients who were allergic to iodinated contrast material and for those with renal insufficiency [152]. It is particularly advantageous in the management of atherosclerotic renal artery stenosis (RAS) and infrarenal abdominal aortic aneurysms [153]. Although CO2 angiography is considered to be a safe and efficacious method for the evaluation of PAD, it has not gained widespread use. Carbon dioxide (CO2) is a highly soluble, invisible gas. When injected into vessels, it briefly displaces the blood before it is rapidly dissolved and eliminated through exhalation. These unique properties of CO2 give it several advantages over other contrast media. Foremost, CO2 is non-allergenic and non-nephrotoxic, making it safe for use in patients with either contrast allergy or kidney disease [154, 155]. Essentially unlimited volumes of CO2 can be used, assuming sufficient time is allowed for the gas to be eliminated from the body. Carbon dioxide even is usually safe in patients with chronic lung disease with CO2 retention, as long as additional time is taken between injections to allow for the gas to be cleared by the lungs [156]. Further benefits include its low viscosity relative to blood, which can aid in the detection of subtle bleeding. Carbon dioxide’s low viscosity additionally can improve visualization of small collateral vessels and aid in identifying distal reconstitution in patients with peripheral arterial disease [155, 157]. Lastly, medical-grade CO2 is very inexpensive compared with iodinated contrast and is readily available.
Limitations and Complications of CO2
Though CO2 angiography has its advantages, it is not without limitations. Given the possibility of neurotoxicity, CO2 cannot be injected or allowed to enter the cerebral circulation. Thus, CO2 should be used only for infra-diaphragmatic arteriography. If large quantities are injected, then undissolved bolus of gas may impede blood flow and produce end organ ischemia. Nondependent locations such as aortic aneurysms, the pulmonary outflow tract, and the mesenteric vessels are most at risk [156].
A prospective multicenter randomized clinical trial of 98 patients (109 lesions) evaluated CO2 angiography-guided endovascular therapy (EVT) in renal and ilio-femoral arteries in patients with CKD. A high procedural success rate was obtained with a minimum amount of iodinated contrast volume. Low incidence of CI-AKI was confirmed in CO2 angiography-guided EVT. However, CO2 angiography carries the risk of severe non-occlusive mesenteric ischemia (NOMI) in rare individuals, which results in high rates of mortality. Finally, visualization may be suboptimal with CO2 angiography. Cautious use of CO2 angiography is warranted at this time [158].
Alternative imaging approaches relying only on intravascular ultrasound have also been suggested for peripheral interventions. One study suggested that peripheral intervention is feasible using duplex ultrasound, MRA, and CT for preprocedural evaluation and intravascular ultrasound to guide the procedure, avoiding intra-arterial contrast injection in selected patients deemed at high risk for renal failure from nephrotoxic contrast material [159]. Other investigators reported that intravascular ultrasound complements the diagnostic capability of CO2 angiography for patients either intolerant to iodinated contrast medium or in those at risk from contrast such as those with CKD [160] .
Use of Dilute Contrast
1:1 dilution of contrast media with saline could technically reduce the amount of contrast usage; however, the operator is still limited with regards to the total volume of contrast that can safely be used without putting patients at risk for CI-AKI. Also, if overly dilute, the contrast may not render optimal image quality in large vessels within the abdomen, thorax, or in lower extremities.
Use of Iso-osmolar and Low Osmolar Contrast Media Agents
The impact of contrast media osmolality on the incidence of CIAKI had been assessed in several randomized trials. In a meta-analysis of the relative nephrotoxicity of the high versus low osmolar agents, reported incidence of contrast-induced AKI events were lower using low osmolar than high osmolar agent (in 25 trials was 0.61 (95% CI: 0.48–0.77) [161]. In another multicenter randomized controlled trial (RCT) of 1196 patients, there was lower incidence of CIN using low osmolar agent in patients with pre-existent renal insufficiency, independent of the presence of diabetes mellitus [162]. In addition to this, several studies have found no differences in the incidence of new onset kidney dysfunction and CI-AKI in comparing low osmolar versus iso-osmolar contrast agents [163].
A cohort study suggested that as compared with low-osmolar contrast media (LOCM), iso-osmolar may be associated with reduction of major adverse renal and cardiovascular events in coronary or peripheral angioplasty patients [164]. The route of administration may have significant implications for iso-osmolar versus low osmolar contrast agents with regards to kidney injury. A meta-analysis of 25 prospective, randomized comparisons between iso-osmolar contrast agent iodixanol and LOCM did find that intra-arterial but not intravenous administration of iodixanol is associated with a significantly lower risk of contrast-induced acute kidney injury than LOCM [165].
Aorto-Iliac Disease
Surgical Techniques
Surgical techniques for aorto-iliac disease include aorto-iliac thrombo-endarterectomy, aorto-bifemoral bypass surgery, and extra anatomic bypass surgery. Extra anatomic bypass surgery includes axillo-femoral and femoro-femoral techniques. Extra anatomic bypass has the advantage of avoiding an open abdominal procedure and thereby the morbidity associated with it; however, long-term patency rates are lower compared with the other approaches. The overall primary patency rates of these grafts are 85–88% over a period of 5 years and decrease to 75–78% by 10 years. The 10-year limb salvage rate and overall survival rates are around 97% and 91% respectively [166].
Endovascular Intervention
Endovascular treatment of extensive aorto-iliac disease can be performed successfully by experienced interventionists in selected patients. Although primary patency rates are lower than those reported for surgical revascularization, re-interventions can often be performed percutaneously, with secondary patency comparable to surgical repair [167, 168].
Meta-analyses indicated that technical success could be achieved in 86–100% of the patients with clinical symptom improvements in 83–100%. Mortality was described in 7 studies and ranged from 1.2% to 6.7%. Complications were reported in 3–45% of the patients. Most common complications were distal embolization, access site hematomas, pseudoaneurysms, arterial ruptures, and arterial dissections. The majority of complications could be treated using percutaneous or noninvasive techniques. Four- or 5-year primary and secondary patency rates ranged from 60% to 94% and 80% to 98%, respectively [166,167,168].
Various stenting options are available for aorto-iliac diseases including self-expandable, balloon expandable, or covered stents. In patients with CKD, heavily calcified lesions in aorto-iliac regions and balloon expandable stents with higher radial force are preferred, whereas larger diameter lesions are better served with self-expandable stents.
Covered stenting of the iliac artery has previously been shown to decrease the need for repeat interventions. However, comparison data with newer coated and self-expandable stents are lacking at this time. For bifurcation aortic disease involving aorta and the iliac ostia, the preferred technique is by way of “aorto-iliac” kissing stents [169]. Given the lack of randomized comparative effectiveness data and the relatively similar patency results of existing second-generation iliac stents in these regulatory single-arm trials, stent choice is largely based on operator experience, familiarity with particular products, ease of deployment, availability, and cost.
Infrainguinal Peripheral Arterial Disease
Clinical Presentation
Symptomatic infrainguinal peripheral arterial disease manifests as claudication of the thighs, calves, non-healing ulcers of lower leg following trauma, and critical limb ischemia. Critical limb ischemia is defined as chronic rest pain, ulcers, gangrene that is attributable to arterial occlusive disease.
Interventional Management
Based on the Trans-Atlantic Inter-Society Consensus (TASC) classification. TASC A, B, and C Infrainguinal diseases are best managed via endovascular therapies, whereas surgical therapies are preferred strategy for TASC D disease. With new improvements in peripheral endovascular techniques and equipment, endovascular management of TASC D lesions is also being performed.
Although symptom and patency outcomes with surgical interventions may be superior to those for less invasive endovascular treatments, surgical interventions are also associated with greater risk of adverse perioperative events [170]. It should be noted at the time the Bypass versus Angioplasty in Severe Ischemia of the Leg (BASIL) trial was performed [171], the angioplasty group did not include stents or other adjunctive procedures; as such, the primary comparison between surgery and angioplasty may not reflect modern endovascular strategies. In the BASIL study, for patients who survived for 2 years after randomization, initial randomization to a bypass surgery-first revascularization strategy was associated with an increase in subsequent restricted mean overall survival of 7.3 months (95% CI, 1.2–13.4 months, p = 0.02) and an increase in restricted mean amputation-free survival of 5.9 months (95% CI, 0.2–12.0 months, p = 0.06) during the subsequent mean follow-up of 3.1 years (range, 1–5.7 years) [171].
Endovascular strategy includes plain balloon angioplasty, bare metal stents, PTFE covered stents, and drug-coated stents [172]. Drug-coated balloons (DCB) have shown superior patency rates compared to plain balloon angioplasty for revascularization of infrapopliteal arteries [173]. These studies suggest that in comparison with uncoated balloons or drug-eluting stents, the treatment of infrapopliteal arteries with DCBs is associated with favorable angiographic efficacy at 1-year follow-up.
Drug-Eluting Stents
Currently there are data from RCT’s and meta-analyses analyzing the results of infra-popliteal drug-eluting stent (DES) versus either PTA or bare metal stents (BMS). Previously, the preferred endovascular approach was PTA alone with BMS reserved in case of a dissection as a “bailout” technique. Clinical data suggested that BMS had little clinical advantage over successful balloon angioplasty in patients with CLI [174].
The preponderance of the evidence for infra-popliteal DES, however, has demonstrated significant benefit over both BMS and PTA for (1) patency, (2) reduced reinterventions, (3) reduced amputation, and (4) improved event-free survival. These results are not specific to CLI, as most trials have included patients with severe claudication.
Surgical Therapy
Surgical bypass grafting using autologous veins versus artificial conduits is limited to TASC D lesions which have failed endovascular therapies. Femoral-popliteal bypass is one of the most common surgical procedures for claudication. The type of conduit and site of popliteal artery anastomosis (above versus below knee) are major determinants of outcomes associated with femoral-popliteal bypass. Systematic reviews and meta-analyses have identified a clear and consistent primary patency benefit for autogenous vein versus prosthetic grafts for popliteal artery bypass [175]. For patients with infrainguinal peripheral arterial disease and CKD requiring percutaneous interventions, judicious use of IVUS and CO2 angiography along with diluted contrast use reduces the risk for further deterioration of renal function. When available, such alternative mode of imaging should be considered as mentioned before.
Peripheral Arterial Disease Outcomes in the Chronic Kidney Disease Population
Traditional CVD risk factors like hypertension, hyperlipidemia, and diabetes do not account for the disproportionately high cardiovascular risk in patients with CKD. In addition, standard clinical interventions for managing CVD, which are successful in the general population, are less effective in lowering mortality and morbidity in patients with CKD with increased risks of complications from interventions. The presence of CKD in patients with PAD not only increases lower extremity amputation rates but also increases the risk of repeat hospitalizations and delayed healing of infected wounds leading to increased incidence of sepsis. Moreover, the presence of CKD even after adjusting for traditional risk factors increases the risk of all-cause mortality and amputations [31]. Also, severe CKD increased the risk of requiring repeat intervention in infrainguinal arteries with previous angioplasty. Among patients who underwent surgical bypass grafting, the trend towards early postoperative re-intervention was higher in patients with severe CKD. Patients with severe CKD are more likely to require multi-level interventions and also two third of them are likely to present calcified below the knee arterial disease resulting in increased risk of intervention failure [31, 39].
Patients with carotid disease with associated CKD appear to have worse prognosis than those without CKD. Patients with severe CKD undergoing carotid interventions have been shown to have statistically significant increased morbidity and mortality (GFR less than 30 ml/min/1.73 m2) (3.1% vs. 1.0% control, p < 0.001) [176]. The 5-year survival rates have been shown to be significantly lower in patients undergoing endarterectomy or carotid stenting, with much worse mortality rates as kidney disease worsens [46, 177].
Conclusions
The combination of CKD and PAD poses a myriad of challenges in managing the dual burden of these diseases effectively. On top of classic atherosclerosis risk factors (age, smoking, diabetes, hypertension, and hyperlipidemia) which are more prevalent in patients with CKD, the chronic inflammatory state and pro-calcific milieu of CKD imposes and accelerates rate of atherosclerosis in these patients. The complexities of managing these co-existing conditions requires early and frequent involvement of multiple specialists including nephrologists, wound care specialists, dieticians, and interventional cardiovascular specialists and/or vascular surgeons. Such a multidisciplinary team approach along with early identification and planned invasive or conservative therapies based on symptomatology and clinical presentation is key to reducing the burden of PAD and its associated adverse outcomes in the CKD population.
References
Mukherjee D, Cho L. Peripheral arterial disease: considerations in risks, diagnosis, and treatment. J Natl Med Assoc. 2009;101(10):999–1008.
Dhaliwal G, Mukherjee D. Peripheral arterial disease: epidemiology, natural history, diagnosis and treatment. Int J Angiol. 2007;16(2):36–44.
Hirsch AT, Hartman L, Town RJ, Virnig BA. National health care costs of peripheral arterial disease in the Medicare population. Vasc Med. 2008;13(3):209–15.
Kalbaugh CA, Kucharska-Newton A, Wruck L, Lund JL, Selvin E, Matsushita K, et al. Peripheral artery disease prevalence and incidence estimated from both outpatient and inpatient settings among medicare fee-for-service beneficiaries in the atherosclerosis risk in communities (ARIC) study. J Am Heart Assoc. 2017;6(5):e003796.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1–266.
System. URD. US renal data system 2016 annual data report epidemiology of kidney disease in the United States. Am J Kidney Dis. 2017;69(3):A1–8.
O'Hare AM, Glidden DV, Fox CS, Hsu CY. High prevalence of peripheral arterial disease in persons with renal insufficiency: results from the National Health and Nutrition Examination Survey 1999-2000. Circulation. 2004;109(3):320–3.
Workgroup KD. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis. 2005;45(4 Suppl 3):S1–153.
Garimella PS, Hart PD, O'Hare A, DeLoach S, Herzog CA, Hirsch AT. Peripheral artery disease and CKD: a focus on peripheral artery disease as a critical component of CKD care. Am J Kidney Dis. 2012;60(4):641–54.
Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108(17):2154–69.
American Diabetes A. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36(4):1033–46.
Murphy D, McCulloch CE, Lin F, Banerjee T, Bragg-Gresham JL, Eberhardt MS, et al. Trends in prevalence of chronic kidney disease in the United States. Ann Intern Med. 2016;165(7):473–81.
Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286(11):1317–24.
Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015;116(9):1509–26.
Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am Coll Cardiol. 2018;71(19):e127–248.
Zhang Y, Moran AE. Trends in the prevalence, awareness, treatment, and control of hypertension among young adults in the United States, 1999 to 2014. Hypertension. 2017;70(4):736–42.
Aronow WS, Ahn C. Frequency of new coronary events in older persons with peripheral arterial disease and serum low-density lipoprotein cholesterol > or = 125 mg/dl treated with statins versus no lipid-lowering drug. Am J Cardiol. 2002;90(7):789–91.
Aronow WS, Nayak D, Woodworth S, Ahn C. Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment. Am J Cardiol. 2003;92(6):711–2.
Agarwal S. The association of active and passive smoking with peripheral arterial disease: results from NHANES 1999-2004. Angiology. 2009;60(3):335–45.
Cronin O, Morris DR, Walker PJ, Golledge J. The association of obesity with cardiovascular events in patients with peripheral artery disease. Atherosclerosis. 2013;228(2):316–23.
Skilton MR, Chin-Dusting JP, Dart AM, Brazionis L, Lantieri O, O'Dea K, et al. Metabolic health, obesity and 9-year incidence of peripheral arterial disease: the D.E.S.I.R. study. Atherosclerosis. 2011;216(2):471–6.
O’Hare AM, Rodriguez RA, Bacchetti P. Low ankle-brachial index associated with rise in creatinine level over time: results from the atherosclerosis risk in communities study. Arch Intern Med. 2005;165(13):1481–5.
Selim G, Stojceva-Taneva O, Zafirovska K, Sikole A, Gelev S, Dzekova P, et al. Inflammation predicts all-cause and cardiovascular mortality in haemodialysis patients. Prilozi. 2006;27(1):133–44.
Gross P, Six I, Kamel S, Massy ZA. Vascular toxicity of phosphate in chronic kidney disease: beyond vascular calcification. Circ J. 2014;78(10):2339–46.
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29–322.
Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013;382(9901):1329–40.
Lavery LA, Hunt NA, Ndip A, Lavery DC, Van Houtum W, Boulton AJ. Impact of chronic kidney disease on survival after amputation in individuals with diabetes. Diabetes Care. 2010;33(11):2365–9.
Shah SK, Bena JF, Allemang MT, Kelso R, Clair DG, Vargas L, et al. Lower extremity amputations: factors associated with mortality or contralateral amputation. Vasc Endovascular Surg. 2013;47(8):608–13.
Rangaswami J, Lerma EV, Ronco C. Cardio-nephrology: confluence of the heart and kidney in clinical practice. Cham: Springer International Publishing; 2017.
Rajagopalan S, Dellegrottaglie S, Furniss AL, Gillespie BW, Satayathum S, Lameire N, et al. Peripheral arterial disease in patients with end-stage renal disease: observations from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Circulation. 2006;114(18):1914–22.
Luders F, Bunzemeier H, Engelbertz C, Malyar NM, Meyborg M, Roeder N, et al. CKD and acute and long-term outcome of patients with peripheral artery disease and critical limb ischemia. Clin J Am Soc Nephrol. 2016;11(2):216–22.
Luders F, Furstenberg T, Engelbertz C, Gebauer K, Meyborg M, Malyar NM, et al. the impact of chronic kidney disease on hospitalized patients with peripheral arterial disease and critical limb ischemia. Angiology. 2017;68(2):145–50.
Cheung AK, Sarnak MJ, Yan G, Dwyer JT, Heyka RJ, Rocco MV, et al. Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients. Kidney Int. 2000;58(1):353–62.
Collins AJ, Foley RN, Chavers B, Gilbertson D, Herzog C, Johansen K, et al. United States renal data system 2011 annual data report: atlas of chronic kidney disease & end-stage renal disease in the United States. Am J Kidney Dis. 2012;59(1 Suppl 1):A7, e1-420.
Liew YP, Bartholomew JR, Demirjian S, Michaels J, Schreiber MJ Jr. Combined effect of chronic kidney disease and peripheral arterial disease on all-cause mortality in a high-risk population. Clin J Am Soc Nephrol. 2008;3(4):1084–9.
Luo Y, Li X, Li J, Wang X, Xu Y, Qiao Y, et al. Peripheral arterial disease, chronic kidney disease, and mortality: the Chinese Ankle Brachial Index Cohort Study. Vasc Med. 2010;15(2):107–12.
Kornitzer M, Dramaix M, Sobolski J, Degre S, De Backer G. Ankle/arm pressure index in asymptomatic middle-aged males: an independent predictor of ten-year coronary heart disease mortality. Angiology. 1995;46(3):211–9.
Howard DP, Banerjee A, Fairhead JF, Hands L, Silver LE, Rothwell PM, et al. Population-based study of incidence, risk factors, outcome, and prognosis of ischemic peripheral arterial events: implications for prevention. Circulation. 2015;132(19):1805–15.
Patel VI, Mukhopadhyay S, Guest JM, Conrad MF, Watkins MT, Kwolek CJ, et al. Impact of severe chronic kidney disease on outcomes of infrainguinal peripheral arterial intervention. J Vasc Surg. 2014;59(2):368–75.
Owens CD, Ho KJ, Kim S, Schanzer A, Lin J, Matros E, et al. Refinement of survival prediction in patients undergoing lower extremity bypass surgery: stratification by chronic kidney disease classification. J Vasc Surg. 2007;45(5):944–52.
Aihara H, Soga Y, Iida O, Suzuki K, Tazaki J, Shintani Y, et al. Long-term outcomes of endovascular therapy for aortoiliac bifurcation lesions in the real-AI registry. J Endovasc Ther. 2014;21(1):25–33.
Patel VI, Lancaster RT, Mukhopadhyay S, Aranson NJ, Conrad MF, LaMuraglia GM, et al. Impact of chronic kidney disease on outcomes after abdominal aortic aneurysm repair. J Vasc Surg. 2012;56(5):1206–13.
Saratzis ASP, Melas N, Saratzis N, Kitas G. Impaired renal function is associated with mortality and morbidity after endovascular abdominal aortic aneurysm repair. J Vasc Surg. 2013;58(4):879–85.
Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, et al. ESC/EAS Guidelines for the management of dyslipidaemias. Rev Esp Cardiol. 2011;64(12):1168 e1–e60.
Lacroix P, Aboyans V, Desormais I, Kowalsky T, Cambou JP, Constans J, et al. Chronic kidney disease and the short-term risk of mortality and amputation in patients hospitalized for peripheral artery disease. J Vasc Surg. 2013;58(4):966–71.
Sidawy AN, Aidinian G, Johnson ON 3rd, White PW, DeZee KJ, Henderson WG. Effect of chronic renal insufficiency on outcomes of carotid endarterectomy. J Vasc Surg. 2008;48(6):1423–30.
Wallaert JB, Cronenwett JL, Bertges DJ, Schanzer A, Nolan BW, De Martino R, et al. Optimal selection of asymptomatic patients for carotid endarterectomy based on predicted 5-year survival. J Vasc Surg. 2013;58(1):112–8.
Protack CD, Bakken AM, Saad WE, Davies MG. Influence of chronic renal insufficiency on outcomes following carotid revascularization. Arch Surg. 2011;146(10):1135–41.
Cronin CT, McCartan DP, McMonagle M, Cross KS, Dowdall JF. Peripheral artery disease: a marked lack of awareness in Ireland. Eur J Vasc Endovasc Surg. 2015;49(5):556–62.
Yu FP, Zhao YC, Gu B, Hu J, Yang YY. Chronic kidney disease and carotid atherosclerosis in patients with acute stroke. Neurologist. 2015;20(2):23–6.
Sacco RL, Kargman DE, Gu Q, Zamanillo MC. Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke. 1995;26(1):14–20.
El Husseini N, Kaskar O, Goldstein LB. Chronic kidney disease and stroke. Adv Chronic Kidney Dis. 2014;21(6):500–8.
Dad T, Weiner DE. Stroke and chronic kidney disease: epidemiology, pathogenesis, and management across kidney disease stages. Semin Nephrol. 2015;35(4):311–22.
Toyoda K, Ninomiya T. Stroke and cerebrovascular diseases in patients with chronic kidney disease. Lancet Neurol. 2014;13(8):823–33.
Wolf PA, Kannel WB, Sorlie P, McNamara P. Asymptomatic carotid bruit and risk of stroke. The Framingham study. JAMA. 1981;245(14):1442–5.
Brott TG, Halperin JL, Abbara S, Bacharach JM, Barr JD, Bush RL, et al. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. Developed in collaboration with the American Academy of Neurology and Society of Cardiovascular Computed Tomography. Catheter Cardiovasc Interv. 2013;81(1):E76–123.
Grant EG, Benson CB, Moneta GL, Alexandrov AV, Baker JD, Bluth EI, et al. Carotid artery stenosis: gray-scale and Doppler US diagnosis--Society of Radiologists in Ultrasound Consensus Conference. Radiology. 2003;229(2):340–6.
Nederkoorn PJ, Mali WP, Eikelboom BC, Elgersma OE, Buskens E, Hunink MG, et al. Preoperative diagnosis of carotid artery stenosis: accuracy of noninvasive testing. Stroke. 2002;33(8):2003–8.
Sabeti S, Schillinger M, Mlekusch W, Willfort A, Haumer M, Nachtmann T, et al. Quantification of internal carotid artery stenosis with duplex US: comparative analysis of different flow velocity criteria. Radiology. 2004;232(2):431–9.
Zwiebel WJ. Duplex sonography of the cerebral arteries: efficacy, limitations, and indications. AJR Am J Roentgenol. 1992;158(1):29–36.
Jahromi AS, Cina CS, Liu Y, Clase CM. Sensitivity and specificity of color duplex ultrasound measurement in the estimation of internal carotid artery stenosis: a systematic review and meta-analysis. J Vasc Surg. 2005;41(6):962–72.
Nederkoorn PJ, van der Graaf Y, Hunink MG. Duplex ultrasound and magnetic resonance angiography compared with digital subtraction angiography in carotid artery stenosis: a systematic review. Stroke. 2003;34(5):1324–32.
Utter GH, Hollingworth W, Hallam DK, Jarvik JG, Jurkovich GJ. Sixteen-slice CT angiography in patients with suspected blunt carotid and vertebral artery injuries. J Am Coll Surg. 2006;203(6):838–48.
Chappell FM, Wardlaw JM, Young GR, Gillard JH, Roditi GH, Yip B, et al. Carotid artery stenosis: accuracy of noninvasive tests--individual patient data meta-analysis. Radiology. 2009;251(2):493–502.
Alvarez-Linera J, Benito-Leon J, Escribano J, Campollo J, Gesto R. Prospective evaluation of carotid artery stenosis: elliptic centric contrast-enhanced MR angiography and spiral CT angiography compared with digital subtraction angiography. AJNR Am J Neuroradiol. 2003;24(5):1012–9.
Cosottini M, Pingitore A, Puglioli M, Michelassi MC, Lupi G, Abbruzzese A, et al. Contrast-enhanced three-dimensional magnetic resonance angiography of atherosclerotic internal carotid stenosis as the noninvasive imaging modality in revascularization decision making. Stroke. 2003;34(3):660–4.
Remonda L, Senn P, Barth A, Arnold M, Lovblad KO, Schroth G. Contrast-enhanced 3D MR angiography of the carotid artery: comparison with conventional digital subtraction angiography. AJNR Am J Neuroradiol. 2002;23(2):213–9.
Wutke R, Lang W, Fellner C, Janka R, Denzel C, Lell M, et al. High-resolution, contrast-enhanced magnetic resonance angiography with elliptical centric k-space ordering of supra-aortic arteries compared with selective x-ray angiography. Stroke. 2002;33(6):1522–9.
Yucel EK, Anderson CM, Edelman RR, Grist TM, Baum RA, Manning WJ, et al. AHA scientific statement. Magnetic resonance angiography: update on applications for extracranial arteries. Circulation. 1999;100(22):2284–301.
Inzitari D, Eliasziw M, Gates P, Sharpe BL, Chan RK, Meldrum HE, et al. The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. 2000;342(23):1693–700.
Eisenberg RL, Bank WO, Hedgcock MW. Neurologic complications of angiography in patients with critical stenosis of the carotid artery. Neurology. 1980;30(8):892–5.
Earnest F, Forbes G, Sandok BA, Piepgras DG, Faust RJ, Ilstrup DM, et al. Complications of cerebral angiography: prospective assessment of risk. AJR Am J Roentgenol. 1984;142(2):247–53.
Dion JE, Gates PC, Fox AJ, Barnett HJ, Blom RJ. Clinical events following neuroangiography: a prospective study. Stroke. 1987;18(6):997–1004.
Grzyska U, Freitag J, Zeumer H. Selective cerebral intraarterial DSA. Complication rate and control of risk factors. Neuroradiology. 1990;32(4):296–9.
Hankey GJ, Warlow CP, Molyneux AJ. Complications of cerebral angiography for patients with mild carotid territory ischaemia being considered for carotid endarterectomy. J Neurol Neurosurg Psychiatry. 1990;53(7):542–8.
Hankey GJ, Warlow CP, Sellar RJ. Cerebral angiographic risk in mild cerebrovascular disease. Stroke. 1990;21(2):209–22.
Leonardi M, Cenni P, Simonetti L, Raffi L, Battaglia S. Retrospective study of complications arising during cerebral and spinal diagnostic angiography from 1998 to 2003. Interv Neuroradiol. 2005;11(3):213–21.
Wehman JC, Hanel RA, Guidot CA, Guterman LR, Hopkins LN. Atherosclerotic occlusive extracranial vertebral artery disease: indications for intervention, endovascular techniques, short-term and long-term results. J Interv Cardiol. 2004;17(4):219–32.
Wityk RJ, Chang HM, Rosengart A, Han WC, DeWitt LD, Pessin MS, et al. Proximal extracranial vertebral artery disease in the New England Medical Center Posterior Circulation Registry. Arch Neurol. 1998;55(4):470–8.
Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005;352(13):1305–16.
Hornig CR, Lammers C, Buttner T, Hoffmann O, Dorndorf W. Long-term prognosis of infratentorial transient ischemic attacks and minor strokes. Stroke. 1992;23(2):199–204.
Glass TA, Hennessey PM, Pazdera L, Chang HM, Wityk RJ, Dewitt LD, et al. Outcome at 30 days in the New England Medical Center Posterior Circulation Registry. Arch Neurol. 2002;59(3):369–76.
Marquardt L, Kuker W, Chandratheva A, Geraghty O, Rothwell PM. Incidence and prognosis of > or = 50% symptomatic vertebral or basilar artery stenosis: prospective population-based study. Brain. 2009;132(Pt 4):982–8.
Long A, Lepoutre A, Corbillon E, Branchereau A. Critical review of non- or minimally invasive methods (duplex ultrasonography, MR- and CT-angiography) for evaluating stenosis of the proximal internal carotid artery. Eur J Vasc Endovasc Surg. 2002;24(1):43–52.
Kaneko Y, Yanagawa T, Taru Y, Hayashi S, Zhang H, Tsukahara T, et al. Subclavian steal syndrome in a hemodialysis patient after percutaneous transluminal angioplasty of arteriovenous access. J Vasc Access. 2018;19:404. https://doi.org/10.1177/1129729818761279.
Cua B, Mamdani N, Halpin D, Jhamnani S, Jayasuriya S, Mena-Hurtado C. Review of coronary subclavian steal syndrome. J Cardiol. 2017;70(5):432–7.
McDermott MM, Mehta S, Greenland P. Exertional leg symptoms other than intermittent claudication are common in peripheral arterial disease. Arch Intern Med. 1999;159(4):387–92.
McDermott MM, Greenland P, Liu K, Guralnik JM, Criqui MH, Dolan NC, et al. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA. 2001;286(13):1599–606.
Khan NA, Rahim SA, Anand SS, Simel DL, Panju A. Does the clinical examination predict lower extremity peripheral arterial disease? JAMA. 2006;295(5):536–46.
Armstrong DW, Tobin C, Matangi MF. The accuracy of the physical examination for the detection of lower extremity peripheral arterial disease. Can J Cardiol. 2010;26(10):e346–50.
Schroder F, Diehm N, Kareem S, Ames M, Pira A, Zwettler U, et al. A modified calculation of ankle-brachial pressure index is far more sensitive in the detection of peripheral arterial disease. J Vasc Surg. 2006;44(3):531–6.
Premalatha G, Ravikumar R, Sanjay R, Deepa R, Mohan V. Comparison of colour duplex ultrasound and ankle-brachial pressure index measurements in peripheral vascular disease in type 2 diabetic patients with foot infections. J Assoc Physicians India. 2002;50:1240–4.
Allen J, Oates CP, Henderson J, Jago J, Whittingham TA, Chamberlain J, et al. Comparison of lower limb arterial assessments using color-duplex ultrasound and ankle/brachial pressure index measurements. Angiology. 1996;47(3):225–32.
Lijmer JG, Hunink MG, van den Dungen JJ, Loonstra J, Smit AJ. ROC analysis of noninvasive tests for peripheral arterial disease. Ultrasound Med Biol. 1996;22(4):391–8.
Guo X, Li J, Pang W, Zhao M, Luo Y, Sun Y, et al. Sensitivity and specificity of ankle-brachial index for detecting angiographic stenosis of peripheral arteries. Circ J. 2008;72(4):605–10.
Niazi K, Khan TH, Easley KA. Diagnostic utility of the two methods of ankle brachial index in the detection of peripheral arterial disease of lower extremities. Catheter Cardiovasc Interv. 2006;68(5):788–92.
Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg. 1997;26(3):517–38.
Eslahpazir BA, Allemang MT, Lakin RO, Carman TL, Trivonovich MR, Wong VL, et al. Pulse volume recording does not enhance segmental pressure readings for peripheral arterial disease stratification. Ann Vasc Surg. 2014;28(1):18–27.
Carter SA, Tate RB. Value of toe pulse waves in addition to systolic pressures in the assessment of the severity of peripheral arterial disease and critical limb ischemia. J Vasc Surg. 1996;24(2):258–65.
Ramsey DE, Manke DA, Sumner DS. Toe blood pressure. A valuable adjunct to ankle pressure measurement for assessing peripheral arterial disease. J Cardiovasc Surg (Torino). 1983;24(1):43–8.
Vincent DG, Salles-Cunha SX, Bernhard VM, Towne JB. Noninvasive assessment of toe systolic pressures with special reference to diabetes mellitus. J Cardiovasc Surg (Torino). 1983;24(1):22–8.
Weinberg I, Giri J, Calfon MA, Hawkins BM, Weinberg MD, Margey R, et al. Anatomic correlates of supra-normal ankle brachial indices. Catheter Cardiovasc Interv. 2013;81(6):1025–30.
Carter SA. Clinical measurement of systolic pressures in limbs with arterial occlusive disease. JAMA. 1969;207(10):1869–74.
Covic A, Kanbay M, Voroneanu L, Turgut F, Serban DN, Serban IL, et al. Vascular calcification in chronic kidney disease. Clin Sci (Lond). 2010;119(3):111–21.
Mahe G, Pollak AW, Liedl DA, Cohoon KP, Mc Carter C, Rooke TW, et al. Discordant diagnosis of lower extremity peripheral artery disease using American Heart Association Postexercise Guidelines. Medicine (Baltimore). 2015;94(31):e1277.
Nicolai SP, Viechtbauer W, Kruidenier LM, Candel MJ, Prins MH, Teijink JA. Reliability of treadmill testing in peripheral arterial disease: a meta-regression analysis. J Vasc Surg. 2009;50(2):322–9.
Laing SP, Greenhalgh RM. Standard exercise test to assess peripheral arterial disease. Br Med J. 1980;280(6206):13–6.
Sumner DS, Strandness DE Jr. The relationship between calf blood flow and ankle blood pressure in patients with intermittent claudication. Surgery. 1969;65(5):763–71.
Biotteau E, Mahe G, Rousseau P, Leftheriotis G, Abraham P. Transcutaneous oxygen pressure measurements in diabetic and non-diabetic patients clinically suspected of severe limb ischemia: a matched paired retrospective analysis. Int Angiol. 2009;28(6):479–83.
Yamada T, Ohta T, Ishibashi H, Sugimoto I, Iwata H, Takahashi M, et al. Clinical reliability and utility of skin perfusion pressure measurement in ischemic limbs--comparison with other noninvasive diagnostic methods. J Vasc Surg. 2008;47(2):318–23.
Castronuovo JJ Jr, Adera HM, Smiell JM, Price RM. Skin perfusion pressure measurement is valuable in the diagnosis of critical limb ischemia. J Vasc Surg. 1997;26(4):629–37.
Bunte MC, Jacob J, Nudelman B, Shishehbor MH. Validation of the relationship between ankle-brachial and toe-brachial indices and infragenicular arterial patency in critical limb ischemia. Vasc Med. 2015;20(1):23–9.
Shishehbor MH, Hammad TA, Zeller T, Baumgartner I, Scheinert D, Rocha-Singh KJ. An analysis of IN.PACT DEEP randomized trial on the limitations of the societal guidelines-recommended hemodynamic parameters to diagnose critical limb ischemia. J Vasc Surg. 2016;63(5):1311–7.
Burbelko M, Augsten M, Kalinowski MO, Heverhagen JT. Comparison of contrast-enhanced multi-station MR angiography and digital subtraction angiography of the lower extremity arterial disease. J Magn Reson Imaging. 2013;37(6):1427–35.
Shareghi S, Gopal A, Gul K, Matchinson JC, Wong CB, Weinberg N, et al. Diagnostic accuracy of 64 multidetector computed tomographic angiography in peripheral vascular disease. Catheter Cardiovasc Interv. 2010;75(1):23–31.
Ota H, Takase K, Igarashi K, Chiba Y, Haga K, Saito H, et al. MDCT compared with digital subtraction angiography for assessment of lower extremity arterial occlusive disease: importance of reviewing cross-sectional images. AJR Am J Roentgenol. 2004;182(1):201–9.
de Vries SO, Hunink MG, Polak JF. Summary receiver operating characteristic curves as a technique for meta-analysis of the diagnostic performance of duplex ultrasonography in peripheral arterial disease. Acad Radiol. 1996;3(4):361–9.
Baril DT, Patel VI, Judelson DR, Goodney PP, McPhee JT, Hevelone ND, et al. Outcomes of lower extremity bypass performed for acute limb ischemia. J Vasc Surg. 2013;58(4):949–56.
Londero LS, Norgaard B, Houlind K. Patient delay is the main cause of treatment delay in acute limb ischemia: an investigation of pre- and in-hospital time delay. World J Emerg Surg. 2014;9(1):56.
Manojlovic V, Popovic V, Nikolic D, Milosevic D, Pasternak J, Kacanski M. Analysis of associated diseases in patients with acute critical lower limb ischemia. Med Pregl. 2013;66(1–2):41–5.
Duval S, Keo HH, Oldenburg NC, Baumgartner I, Jaff MR, Peacock JM, et al. The impact of prolonged lower limb ischemia on amputation, mortality, and functional status: the FRIENDS registry. Am Heart J. 2014;168(4):577–87.
Morris-Stiff G, D’Souza J, Raman S, Paulvannan S, Lewis MH. Update experience of surgery for acute limb ischaemia in a district general hospital - are we getting any better? Ann R Coll Surg Engl. 2009;91(8):637–40.
Nigwekar SU, Thadhani R, Brandenburg VM. Calciphylaxis. N Engl J Med. 2018;379(4):399–400.
Shankar AKR, Klein BE. The association among smoking, heavy drinking, and chronic kidney disease. Am J Epidemiol. 2006;164(3):263–71.
Hennrikus D, Joseph AM, Lando HA, Duval S, Ukestad L, Kodl M, et al. Effectiveness of a smoking cessation program for peripheral artery disease patients: a randomized controlled trial. J Am Coll Cardiol. 2010;56(25):2105–12.
Mukherjee D, Yadav JS. Update on peripheral vascular diseases: from smoking cessation to stenting. Cleve Clin J Med. 2001;68(8):723–33.
Feringa HH, Bax JJ, Hoeks S, van Waning VH, Elhendy A, Karagiannis S, et al. A prognostic risk index for long-term mortality in patients with peripheral arterial disease. Arch Intern Med. 2007;167(22):2482–9.
Sung JH, Lee JE, Samdarshi TE, Nagarajarao HS, Taylor JK, Agrawal KK, et al. C-reactive protein and subclinical cardiovascular disease among African-Americans: (the Jackson Heart Study). J Cardiovasc Med (Hagerstown). 2014;15(5):371–6.
Feringa HH, van Waning VH, Bax JJ, Elhendy A, Boersma E, Schouten O, et al. Cardioprotective medication is associated with improved survival in patients with peripheral arterial disease. J Am Coll Cardiol. 2006;47(6):1182–7.
Bavry AA, Anderson RD, Gong Y, Denardo SJ, Cooper-Dehoff RM, Handberg EM, et al. Outcomes Among hypertensive patients with concomitant peripheral and coronary artery disease: findings from the INternational VErapamil-SR/Trandolapril STudy. Hypertension. 2010;55(1):48–53.
Paravastu SC, Mendonca DA, Da Silva A. Beta blockers for peripheral arterial disease. Cochrane Database Syst Rev. 2013;(9):CD005508.
Beebe HG, Dawson DL, Cutler BS, Herd JA, Strandness DE Jr, Bortey EB, et al. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med. 1999;159(17):2041–50.
Benjo AM, Garcia DC, Jenkins JS, Cardoso RM, Molina TP, El-Hayek GE, et al. Cilostazol increases patency and reduces adverse outcomes in percutaneous femoropopliteal revascularisation: a meta-analysis of randomised controlled trials. Open Heart. 2014;1(1):e000154.
Jaff MR, White CJ, Hiatt WR, Fowkes GR, Dormandy J, Razavi M, et al. An update on methods for revascularization and expansion of the TASC lesion classification to include below-the-knee arteries: a supplement to the inter-society consensus for the management of peripheral arterial disease (TASC II): the TASC Steering Comittee(.). Ann Vasc Dis. 2015;8(4):343–57.
Hiatt WR, Regensteiner JG, Hargarten ME, Wolfel EE, Brass EP. Benefit of exercise conditioning for patients with peripheral arterial disease. Circulation. 1990;81(2):602–9.
Hiatt WR, Wolfel EE, Meier RH, Regensteiner JG. Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease. Implications for the mechanism of the training response. Circulation. 1994;90(4):1866–74.
Olin JW, White CJ, Armstrong EJ, Kadian-Dodov D, Hiatt WR. Peripheral artery disease: evolving role of exercise, medical therapy, and endovascular options. J Am Coll Cardiol. 2016;67(11):1338–57.
Murphy TP, Cutlip DE, Regensteiner JG, Mohler ER 3rd, Cohen DJ, Reynolds MR, et al. Supervised exercise, stent revascularization, or medical therapy for claudication due to aortoiliac peripheral artery disease: the CLEVER study. J Am Coll Cardiol. 2015;65(10):999–1009.
Guzman RJ, Brinkley DM, Schumacher PM, Donahue RM, Beavers H, Qin X. Tibial artery calcification as a marker of amputation risk in patients with peripheral arterial disease. J Am Coll Cardiol. 2008;51(20):1967–74.
Goldenberg I, Matetzky S. Nephropathy induced by contrast media: pathogenesis, risk factors and preventive strategies. CMAJ. 2005;172(11):1461–71.
Tepel M, Aspelin P, Lameire N. Contrast-induced nephropathy: a clinical and evidence-based approach. Circulation. 2006;113(14):1799–806.
Lameire NH. Contrast-induced nephropathy--prevention and risk reduction. Nephrol Dial Transplant. 2006;21(6):i11–23.
Blandon J, Mukherjee D. Current approaches to prevention of contrast induced acute kidney injury. Cardiovasc Hematol Agents Med Chem. 2011;9(4):247–52.
McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F, et al. Risk prediction of contrast-induced nephropathy. Am J Cardiol. 2006;98(6A):27K–36K.
Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002;105(19):2259–64.
Kagan A, Sheikh-Hamad D. Contrast-induced kidney injury: focus on modifiable risk factors and prophylactic strategies. Clin Cardiol. 2010;33(2):62–6.
Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol. 2004;44(7):1393–9.
Rashid ST, Salman M, Myint F, Baker DM, Agarwal S, Sweny P, et al. Prevention of contrast-induced nephropathy in vascular patients undergoing angiography: a randomized controlled trial of intravenous N-acetylcysteine. J Vasc Surg. 2004;40(6):1136–41.
Waybill MM, Waybill PN. Contrast media-induced nephrotoxicity: identification of patients at risk and algorithms for prevention. J Vasc Interv Radiol. 2001;12(1):3–9.
Cigarroa RG, Lange RA, Williams RH, Hillis LD. Dosing of contrast material to prevent contrast nephropathy in patients with renal disease. Am J Med. 1989;86(6 Pt 1):649–52.
Gurm HS, Dixon SR, Smith DE, Share D, Lalonde T, Greenbaum A, et al. Renal function-based contrast dosing to define safe limits of radiographic contrast media in patients undergoing percutaneous coronary interventions. J Am Coll Cardiol. 2011;58(9):907–14.
Hawkins IF. Carbon dioxide digital subtraction arteriography. AJR Am J Roentgenol. 1982;139(1):19–24.
Chao A, Major K, Kumar SR, Patel K, Trujillo I, Hood DB, et al. Carbon dioxide digital subtraction angiography-assisted endovascular aortic aneurysm repair in the azotemic patient. J Vasc Surg. 2007;45(3):451–8; discussion 8-60.
Hawkins IF, Caridi JG. Carbon dioxide (CO2) digital subtraction angiography: 26-year experience at the University of Florida. Eur Radiol. 1998;8(3):391–402.
Seeger JM, Self S, Harward TR, Flynn TC, Hawkins IF Jr. Carbon dioxide gas as an arterial contrast agent. Ann Surg. 1993;217(6):688–97; discussion 97-8.
Caridi JG, Hawkins IF Jr. CO2 digital subtraction angiography: potential complications and their prevention. J Vasc Interv Radiol. 1997;8(3):383–91.
Coffey R, Quisling RG, Mickle JP, Hawkins IF Jr, Ballinger WB. The cerebrovascular effects of intraarterial CO2 in quantities required for diagnostic imaging. Radiology. 1984;151(2):405–10.
Fujihara M, Kawasaki D, Shintani Y, Fukunaga M, Nakama T, Koshida R, et al. Endovascular therapy by CO2 angiography to prevent contrast-induced nephropathy in patients with chronic kidney disease: a prospective multicenter trial of CO2 angiography registry. Catheter Cardiovasc Interv. 2015;85(5):870–7.
Kawasaki D, Fujii K, Fukunaga M, Fujii N, Masutani M, Kawabata ML, et al. Preprocedural evaluation and endovascular treatment of iliofemoral artery disease without contrast media for patients with pre-existing renal insufficiency. Circ J. 2011;75(1):179–84.
Kusuyama T, Iida H, Mitsui H. Intravascular ultrasound complements the diagnostic capability of carbon dioxide digital subtraction angiography for patients with allergies to iodinated contrast medium. Catheter Cardiovasc Interv. 2012;80(6):E82–6.
Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology. 1993;188(1):171–8.
Rudnick MR, Goldfarb S, Wexler L, Ludbrook PA, Murphy MJ, Halpern EF, et al. Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: a randomized trial. The Iohexol Cooperative study. Kidney Int. 1995;47(1):254–61.
Bertrand ME, Esplugas E, Piessens J, Rasch W. Influence of a nonionic, iso-osmolar contrast medium (iodixanol) versus an ionic, low-osmolar contrast medium (ioxaglate) on major adverse cardiac events in patients undergoing percutaneous transluminal coronary angioplasty: a multicenter, randomized, double-blind study. Visipaque in Percutaneous Transluminal Coronary Angioplasty [VIP] Trial Investigators. Circulation. 2000;101(2):131–6.
McCullough PA, David G, Todoran TM, Brilakis ES, Ryan MP, Gunnarsson C. Iso-osmolar contrast media and adverse renal and cardiac events after percutaneous cardiovascular intervention. J Comp Eff Res. 2018;7(4):331–41.
McCullough PA, Brown JR. Effects of intra-arterial and intravenous iso-osmolar contrast medium (iodixanol) on the risk of contrast-induced acute kidney injury: a meta-analysis. Cardiorenal Med. 2011;1(4):220–34.
Lee GC, Yang SS, Park KM, Park Y, Kim YW, Park KB, et al. Ten year outcomes after bypass surgery in aortoiliac occlusive disease. J Korean Surg Soc. 2012;82(6):365–9.
Jongkind V, Akkersdijk GJ, Yeung KK, Wisselink W. A systematic review of endovascular treatment of extensive aortoiliac occlusive disease. J Vasc Surg. 2010;52(5):1376–83.
Krol KL, Saxon RR, Farhat N, Botti CF, Brown OW, Zemel G, et al. Clinical evaluation of the Zilver vascular stent for symptomatic iliac artery disease. J Vasc Interv Radiol. 2008;19(1):15–22.
Ponec D, Jaff MR, Swischuk J, Feiring A, Laird J, Mehra M, et al. The Nitinol SMART stent vs Wallstent for suboptimal iliac artery angioplasty: CRISP-US trial results. J Vasc Interv Radiol. 2004;15(9):911–8.
Adam DJ, Beard JD, Cleveland T, Bell J, Bradbury AW, Forbes JF, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet. 2005;366(9501):1925–34.
Bradbury AW, Adam DJ, Bell J, Forbes JF, Fowkes FG, Gillespie I, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL) trial: an intention-to-treat analysis of amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon angioplasty-first revascularization strategy. J Vasc Surg. 2010;51(5 Suppl):5S–17S.
Dake MD, Ansel GM, Jaff MR, Ohki T, Saxon RR, Smouse HB, et al. Sustained safety and effectiveness of paclitaxel-eluting stents for femoropopliteal lesions: 2-year follow-up from the Zilver PTX randomized and single-arm clinical studies. J Am Coll Cardiol. 2013;61(24):2417–27.
Cassese S, Ndrepepa G, Liistro F, Fanelli F, Kufner S, Ott I, et al. Drug-coated balloons for revascularization of infrapopliteal arteries: a meta-analysis of randomized trials. JACC Cardiovasc Interv. 2016;9(10):1072–80.
Siablis D, Kitrou PM, Spiliopoulos S, Katsanos K, Karnabatidis D. Paclitaxel-coated balloon angioplasty versus drug-eluting stenting for the treatment of infrapopliteal long-segment arterial occlusive disease: the IDEAS randomized controlled trial. JACC Cardiovasc Interv. 2014;7(9):1048–56.
Albers M, Romiti M, Brochado-Neto FC, Pereira CA. Meta-analysis of alternate autologous vein bypass grafts to infrapopliteal arteries. J Vasc Surg. 2005;42(3):449–55.
Nathan DP, Tang GL. The impact of chronic renal insufficiency on vascular surgery patient outcomes. Semin Vasc Surg. 2014;27(3–4):162–9.
Patel AR, Dombrovskiy VY, Vogel TR. A contemporary evaluation of carotid endarterectomy outcomes in patients with chronic kidney disease in the United States. Vascular. 2017;25(5):459–65.
Norgren L, et al. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg. 2007;45(Suppl S):S5–67.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Nagarajarao, H.S., Ojha, C., Kedar, A., Mukherjee, D. (2020). Peripheral Arterial Disease in Chronic Kidney Disease: Disease Burden, Outcomes, and Interventional Strategies. In: Rangaswami, J., Lerma, E., McCullough, P. (eds) Kidney Disease in the Cardiac Catheterization Laboratory . Springer, Cham. https://doi.org/10.1007/978-3-030-45414-2_3
Download citation
DOI: https://doi.org/10.1007/978-3-030-45414-2_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-45413-5
Online ISBN: 978-3-030-45414-2
eBook Packages: MedicineMedicine (R0)