Cholesterol crystal embolism-related cerebral infarction (CCE-CI) is frequently misdiagnosed due to the lack of specific symptoms. To aid in differential diagnosis, this study comprehensively characterized the magnetic resonance imaging (MRI) and clinical manifestations of CCE-CI and compared these features to those of atherothrombotic cerebral infarction (ACI).

This single-center, retrospective, observational study was conducted at Kitasato University Hospital, Kanagawa, Japan. We identified 37 clinically or histopathologically confirmed CCE-CI cases and 110 ACI cases treated from January 2006 to May 2020. Groups were compared for mean age, sex ratio, clinical presentations, imaging manifestations, precipitating factors, comorbid conditions, medications, and smoking history.

Of 37 eligible patients with CCE-CI, 10 (27.0%) received brain MRI, of which 8 (21.6%) exhibited high-intensity signals indicative of brain lesions on diffusion-weighted imaging (DWI). However, two patients with DWI lesions exhibited no detectable neurological abnormalities. Patients with CCE-CI frequently demonstrated bilateral DWI lesions involving the bilateral anterior and posterior circulation, a pattern absent in ACI (50% vs. 0%, p < 0.001). Compared to patients with ACI, CCE-CI patients also demonstrated significantly lower estimated glomerular filtration rate (p < 0.001) as well as more frequent eosinophilia (p = 0.006), atherosclerotic plaques ≥4-mm thick in the ascending aorta or proximal arch (p = 0.001), and aortic aneurysm (p < 0.001).

Patients with CCE-CI develop multiple DWI lesions across several vascular territories, even in the absence of neurological symptoms. Comorbid aortic aneurysm may increase CCE-CI risk. These findings could help in the differential diagnosis of CCE-CI.

We investigated the predictors, aetiology and long-term outcomes of acute kidney injury (AKI) following urgent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Acute kidney injury occurred in 198 (7.2%) of 2917 patients: 14.1% of AKI cases were attributed to cardiogenic shock and 5.1% were classified as atheroembolic renal disease (AERD). Significant risk factors for AKI included age (odds ratio [OR] 1.05, 95% confidence limits [CI] 1.03-1.06), diabetes (OR 1.73, 95% CI 1.20-2.47), hypertension (OR 1.43, 95% CI 1.03-2.00), heart failure (OR 3.01, 95% CI 1.58-5.57), femoral access (OR 1.50, 95% CI 1.03-2.15), cardiogenic shock (OR 2.03, 95% CI 1.19-3.37) and ST-elevation myocardial infarction (STEMI) (OR 3.89, 95% CI 2.80-5.47). One-year mortality after AERD was 44.4% and renal replacement therapy (RRT) requirement 22.2% (compared with mortality 33.3% and RRT requirement 7.4%, respectively, in all other AKI patients). Mortality at 1 year was associated with AKI (OR 4.33, 95% CI 2.89-6.43), age (OR 1.08, 95% CI 1.06-1.09), heart failure (OR 1.92, 95% CI 1.05-3.44), femoral access (OR 2.05, 95% CI 1.41-2.95) and cardiogenic shock (OR 3.63, 95% CI 2.26-5.77). Acute kidney injury after urgent PCI is strongly associated with worse outcomes. Atheroembolic renal disease has a poor outcome and a high likelihood of long-term RRT requirement.

Atheroembolic renal disease (AERD) is caused by occlusion of the small renal arteries from embolized cholesterol crystals arising from ulcerated atherosclerotic plaques. This usually manifests as isolated renal disease or involvement from systemic atheroembolic disease. Here we report a case of AERD that responded well to steroid therapy.

A 62-year-old woman with a history of hypertension and stage IIIa chronic kidney disease was referred for rapidly worsening renal function over a 4-mo period. She complained of swollen legs, dyspnea on exertion, and two episodes of epistaxis about a month prior to admission. She reported no history of invasive vascular procedures, use of radio contrast agents, or treatment with anticoagulants or thrombolytic agents. Urinalysis showed a few red blood cells and granular casts. Serology was positive for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). Non-contrast-enhanced computed tomography of the chest, abdomen, and pelvis showed diffuse atherosclerotic changes in the aortic arch. Thus, c-ANCA-associated vasculitis was suspected, and the patient was started on pulse intravenous methylprednisolone. Her renal biopsy showed evidence of AERD. She was discharged with oral prednisone, and her renal function continued to improve during the initial follow-up.

In cases of non-vasculitis-associated ANCA, a high degree of clinical suspicion is required to pursue the diagnosis of spontaneous AERD in patients with clinical or radiological evidence of atherosclerotic burden. Although no specific treatment is available, the potential role of statins and steroids requires exploration.

Atheroembolic renal disease (AERD) is a kidney manifestation of atherosclerosis as a systemic disease. AERD is defined as a renal impairment secondary to embolization of cholesterol crystals with consequent occlusion of renal vascularization. The current case report describes one patient with multiple risk factors but without any inciting event history who presents a very atypical clinical course of a severe and massive atheroembolic disease that developed spontaneously and silently.

Drugs such as corticosteroids and statins have been used to treat cholesterol crystal embolism (CCE), but the prognosis remains poor. This study evaluated the efficacy of low-density lipoprotein apheresis (LDL-A) in patients with CCE. Patients with CCE who showed renal deterioration after vascular interventions were studied retrospectively. Information on demographic variables, clinical measurements, and medication use was collected. The outcomes were incidence of maintenance dialysis and mortality at 24 weeks. A total of 49 patients with CCE were included, among whom 37 (76%) were diagnosed pathologically and the remainder were diagnosed clinically. The median estimated GFR at baseline and at diagnosis were 40.5 and 13.4 mL/min per 1.73 m(2) , respectively. Corticosteroids were used in 42 patients (86%), statins in 30 patients (61%), and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in 29 patients (59%). LDL-A was performed in 25 patients (LDL-A group), and not in 24 patients (control group). Smoking (100% vs. 72%, P = 0.02), white blood cell count (8900/mm(3) vs. 7000/mm(3) ) and corticosteroid use (96% vs. 75%) were higher in the LDL-A group compared with the control group, but there were no differences in other demographic and clinical parameters between the groups. Patients in the LDL-A group had a lower incidence of maintenance dialysis (2/25 (8%) vs. 8/24 (33%), P < 0.05), and a trend towards lower mortality (2/25 (8%) vs. 7/24 (29%), P = 0.074). These results suggest that LDL-A decreases the risk of maintenance dialysis in severe renal CCE patients after vascular interventions.

Cholesterol embolization syndrome (CES) is a complication sometimes occurring after invasive endovascular procedures. CES is characterized by release of cholesterol crystals and particles from atheromatous plaques, which can occlude distal vessels and induce an inflammatory response, resulting in end-organ damage. We report the case of a 66-year-old man who presented with an acute ST-elevation myocardial infarction. An intra-aortic balloon pump was placed due to hemodynamic instability following percutaneous coronary intervention. Ten weeks after discharge, he presented with signs and symptoms of CES (e.g., livedo reticularis, acrocyanosis, acute renal failure), and a new left ventricular apical thrombus. Withdrawal of anticoagulation is often recommended in the setting of CES, on the presumption that anticoagulants favor plaque hemorrhage and subsequent cholesterol micro-embolization. Because of the potential disastrous consequences of an embolus, the patient was anticoagulated with warfarin concurrently with corticosteroids to suppress the inflammatory response to cholesterol crystals. His renal function continued to improve and was discharged without the need for dialysis. This case illustrates that anticoagulation therapy in CES is feasible and appears to be safe in patients with a coexisting urgent indication for anticoagulation.

Atheroembolic renal disease is caused by foreign-body reaction to cholesterol crystals flushed from the atherosclerotic plaques into the small-vessel system of the kidneys. It is an underdiagnosed entity, mostly related to vascular procedures and/or anticoagulation, and prognosis is considered to be poor. Besides the benefit of aggressive medical prevention of further embolic events, use of steroid therapy has been associated with greater survival. Here we report a case of a patient with a multisystemic presentation of the disease days after performance of percutaneous coronary intervention and anticoagulation initiation due to an episode of myocardial infarction. Renal, cutaneous, ophthalmic, neurological, and possibly muscular and mesenteric involvement was diagnosed. Although medical treatment with corticosteroids and avoidance of further anticoagulation was applied, the patient rapidly progressed to end-stage renal disease requiring hemodialysis and died 6 months after diagnosis. This is a case of catastrophic progression of the disease resistant to therapeutic measures. Focus on diagnosis and more efficient preventive and therapeutic protocols are therefore needed.

Atheroembolic renal disease develops when atheromatous aortic plaques rupture, releasing cholesterol crystals into the small renal arteries. Embolisation often affects other organs, such as the skin, gastrointestinal system, and brain. Although the disease can develop spontaneously, it usually develops after vascular surgery, catheterisation, or anticoagulation. The systemic nature of atheroembolism makes diagnosis difficult. The classic triad of a precipitating event, acute or subacute renal failure, and skin lesions, are strongly suggestive of the disorder. Eosinophilia further supports the diagnosis, usually confirmed by biopsy of an affected organ or by the fundoscopic finding of cholesterol crystals in the retinal circulation. Renal and patient prognosis are poor. Treatment is mostly preventive, based on avoidance of further precipitating factors, and symptomatic, aimed to the optimum treatment of hypertension and cardiac and renal failure. Statins, which stabilise atherosclerotic plaques, should be offered to all patients. Steroids might have a role in acute or subacute progressive forms with systemic inflammation.

Diagnosis of atheroembolic disease (AD) is challenging, because no specific test is available and AD often masquerades as other clinical conditions. We conducted the current study to investigate the relative frequency of autopsy-proven AD over time, to describe its clinical presentation, and to identify risk factors for AD. We screened 2066 autopsy reports from 1995 to 2006 for AD. For each AD case, a control patient without AD was matched for age, sex, and autopsy year. Diagnostic and therapeutic interventions (surgery, catheter interventions, and drug treatment) in the last 6 months before death, as well as clinical and laboratory parameters during the last hospitalization, were retrieved from electronic charts. We identified 51 patients with AD. Among these only 6 (12%) had been diagnosed clinically. The organs most often affected were kidney (71%), spleen (37%), and lower gastrointestinal tract (22%). The relative AD frequency decreased over time from 3.5 to 0.5 per 100 autopsies, whereas the frequency of clinically suspected and biopsy-proven AD remained constant. Among clinical signs, skin lesions such as livedo reticularis and blue toe (33% vs. 14%; p = 0.04) were significantly increased in AD patients compared with the matched controls. We also observed a trend for higher incidence of eosinophilia and proteinuria in AD patients. Vascular interventions within 6 months before death were highly associated with AD (55% vs. 29%; p = 0.01), and in a multivariable analysis this remained the only significant risk factor for AD. Thus, the diagnosis of AD is frequently missed. Vascular interventions represent the most important risk factor for AD and should be performed restrictively in high-risk patients.

Cholesterol crystal embolism (CCE) is a complication of atherosclerosis. Vascular surgery, vascular angiography, and anticoagulation have been identified as inciting factors.

This paper sought to analyze the clinical characteristics of patients with CCE after percutaneous coronary intervention.

Six patients with atherosclerosis presenting with simultaneous occurrence of acute renal failure and peripheral ischemic changes were diagnosed with CCE and their clinical data were analyzed.

The average age of the patients was 72 years. Most had risk factors of atherosclerosis such as hypertension, diabetes, and smoking. The levels of serum creatinine increased progressively after coronary angiography. All patients had concomitant skin lesions, including blue toes. Cholesterol crystal emboli were found in arterioles by cutaneous biopsy in one patient. All patients received statins and two of these received dialysis therapy. Three patients died and three remained in chronic renal failure.

Since CCE is a severe complication of coronary intervention, special attention should be paid to this disease.

Cholesterol crystal embolization (CCE) is a dreaded complication of radiology, vascular surgery, and/or anticoagulation in patients with atherosclerosis and ulcerated aortic plaques. It also represents a cause of early graft failure and of poor results of renal artery surgery. Crystals lodge in small caliber renal arteries, where they induce early, transitory thrombosis followed by delayed, definitive obstruction by endarteritis, accompanied by evidence of inflammation and eosinophilia. Massive CCE leads to early oligoanuria. In subacute forms, renal insufficiency is often delayed by weeks or months following the triggering event. A third, chronic subset of CCE is easily mistaken for atherosclerotic renal ischemia and/or nephrosclerosis. The kidney is rarely the sole organ involved in acute/subacute forms, in which the central nervous system, the coronary arteries, the spinal cord, and the mesenteric and pancreatic blood supply compromise represent the main causes of death. Cutaneous, retinal, and muscle involvement allow diagnosis by inspection or scarcely invasive biopsies in about 80% of cases, whereas renal biopsy as the only diagnostic procedure is required in 20% of cases. Prevention is based on avoidance of endovascular radiology maneuvers, vascular surgery, and excess anticoagulation in atherosclerotic patients. Treatment of acute/subacute forms of renal insufficiency consisting of stopping anticoagulation and forbidding any new radiologic and/or vascular surgery procedure; treating hypertension with angiotensin 2 antagonists and vasodilators, strict volemic control by loop diuretics and ultrafiltration, along with parenteral nutrition and prednisone, has been credited with improved outcome. Iloprost may obtain favorable results. Statins definitely ameliorate the renal and patient's prognosis.

Atherosclerotic renal artery disease increasingly is recognized as a cause of chronic kidney disease and associated with high morbidity and mortality. We investigated factors predicting patient and renal survival in a cohort of patients with atherosclerotic renal artery disease diagnosed by means of magnetic resonance angiography (MRA).

We retrospectively analyzed a cohort of patients attending our unit in whom atherosclerotic renal artery disease was identified by means of MRA from 1998 to 2001. One hundred nine patients were followed up for a median of 2.3 years. Baseline clinical and laboratory data were assessed as predictors of outcome by using multivariate Cox proportional hazards analysis.

Seventeen patients (16%) required dialysis and 37 patients (34%) died during a median follow-up of 841 days (interquartile range, 326 to 1,206). On multivariate Cox proportional hazards analysis, increased peripheral-blood eosinophil count (hazard ratio, 3.39; 95% confidence interval [CI], 1.45 to 7.88; P = 0.0097), creatinine clearance (hazard ratio, 0.97; 95% CI, 0.94 to 0.99; P = 0.0128), and peripheral arterial disease (hazard ratio, 2.09; 95% CI, 1.04 to 4.18; P = 0.0371) were associated with subsequent death. Only creatinine clearance (hazard ratio, 0.91; 95% CI, 0.87 to 0.96; P = 0.0004) was associated with the need for dialysis. There was no association between eosinophil count and other markers of inflammation. Severity of atherosclerotic renal artery disease was not associated independently with either the need for dialysis or death.

An increased peripheral-blood eosinophil count predicts patient survival in those with atherosclerotic renal artery disease at the time of diagnosis. This novel risk factor may help identify a group of patients who could benefit from intensive medical therapy by using an assay readily available to most clinicians worldwide.

Diffuse atherosclerosis entails a 15-30% risk of plaques on renal arteries (ARAS), with a correlation with coronary atherosclerosis. Ischemia induces generation of angiotensin II (Ang II) that maintains sufficient hydrostatic pressure within the tuft to preserve the GFR. Ang II inhibition suppresses this protective mechanism. In fact, any antihypertensive drug may lead to reaching a "critical perfusion pressure". ARAS should be suspected in case of renal asymmetry. It should also be envisaged in case of "flash pulmonary edemas". Ultrasonography and renal tomography show aortic calcifications and often the outline of an abdominal aortic aneurysm. Tomodensitometry may detect large aorto-renal plaques. Spiral scanner tomography represents a progress, in terms of renal artery imaging and of renal cortical atrophy. Magnetic resonance imaging is less accurate but avoids iodine toxicity. The best noninvasive method is pulsed echo-doppler. It is particularly useful for evaluating stenoses progression. Some stenoses progress to renal atrophy and renal artery thrombosis, whereas others follow a stable course. Pulsed Doppler helps predict whether revascularization will improve renal function, according to the resistance index. Renal arteriography entails a high risk of cholesterol crystal embolism. However, it is the obligatory first step for angioplasty and stent positioning, indicated when the kidney is not atrophic. The indication for revascularization essentially depends on evaluation of the benefits vs risks of angioplasty or surgery. Some publications underscore the frequent stability of renal function and the fact that, revascularized or not, most patients will shortly die of myocardial infarction. Renal cholesterol crystal embolism (CCE) is a severe condition, which occurs when large arteries undergo surgery, aortography or interventional radiology. Anticoagulants are a frequent cause of CCE. CCE may also occur spontaneously, resulting in slowly progressive renal insufficiency. Migration of crystals in small caliber intrarenal arteries induces obstruction, followed by an inflammatory reaction. The clinical picture resembles angiitis, with laboratory evidence of inflammation along with high eosinophil counts and hypocomplementemia. Diagnosis rests on: 1) a iatrogenic event in a patient with an atherosclerotic background; 2) examination of the skin disclosing purple toes, small necrotic lesions and livedo of the lower limbs. Crystals may also be found by funduscopy. Skin or muscle biopsy are contributive in showing crystals and help avoid renal biopsy; 3) other localizations involve the mesenteric circulation and the central nervous system. Until recently, the prognosis was considered disastrous. However, a recently published treatment schedule proved efficient in reducing mortality. A last issue regarding the relationships between atherosclerosis and the kidney deserves mention. In an autopsy-based study it was shown that atherosclerosis per se is accompanied by an increase in the glomerular surface area along with a greater proportion of obsolescent glomeruli by comparison with matched controls. Finally, it should be recalled that atherogenic hyperlipidemia usually aggravates the course of any renal disease, including ARAS. Treatment with statins is indicated in all forms of atherosclerotic renal disease.

Atheromatous embolism is a systemic disease resulting from cholesterol crystal embolization in many organs, including the kidneys. To characterize atheroembolic renal disease (AERD), we retrospectively evaluated 11 patients with acute renal failure after vascular surgery, vascular radiology investigations, and anticoagulation at Miyazaki Medical College from 1994 to 2001. The diagnosis of cholesterol atheromatous embolism was confirmed by tissue examination or clinical grounds. The patients were all elderly men (average age of 66.8 years) with a history of hypertension (55%), diabetes mellitus (45%), hyperlipidemia (45%), and coronary artery disease (18%). Seven patients had livedo reticularis, and 4 had blood eosinophilia. Clinically, 7 patients were managed conservatively and 5 of them improved, whereas 4 patients required dialysis and developed chronic renal failure or died. The serum creatinine levels of the improved patients were significantly lower (1.28+/-0.3 mg/dl, p < 0.005) than the non-improved ones (7.70+/-3.6). The number of eosinophils was significantly higher in the improved patients (576+/-295 /ml, p < 0.05) than in the non-improved ones (208+/-206). However, no significant difference was observed in the levels of serum cholesterol and C-reactive protein among these patients. Since the population at risk for AERD is growing, we should recognize this disease as a cause of acute renal failure.

Cholesterol embolization syndrome is a systemic disease caused by distal showering of cholesterol crystals after angiography, major vessel surgery, or thrombolysis.

We prospectively evaluated a total of 1,786 consecutive patients 40 years of age and older, who underwent left-heart catheterization at 11 participating hospitals. The diagnosis of CES was made when patients had peripheral cutaneous involvement (livedo reticularis, blue toe syndrome, and digital gangrene) or renal dysfunction.

Twenty-five patients (1.4%) were diagnosed as having CES. Twelve patients (48%) had cutaneous signs, and 16 patients (64%) had renal insufficiency. Eosinophil counts were significantly higher in CES patients than in non-CES patients before and after cardiac catheterization. The in-hospital mortality rate was 16.0% (4 patients), which was significantly higher than that without CES (0.5%, p < 0.01). All four patients with CES who died after cardiac catheterization had progressive renal dysfunction. The incidence of CES increased in patients with atherosclerotic disease, hypertension, a history of smoking, and the elevation of baseline plasma C-reactive protein (CRP) by univariate analysis. The femoral approach did not increase the incidence, suggesting a possibility that the ascending aorta may be a potential embolic source. As an independent predictor of CES, multivariate regression analysis identified only the elevation of pre-procedural CRP levels (odds ratio 4.6, P = 0.01).

Cholesterol embolization syndrome is a relatively rare but serious complication after cardiac catheterization. Elevated plasma levels of pre-procedural CRP are associated with subsequent CES in patients who undergo vascular procedures.

We describe the clinical case of a patient with acute myocardial infarction treated with t-PA fibrinolysis, who developed renal failure and cutaneous lesions of the livedo reticularis type, probably caused by embolization of cholesterol crystals. The main characteristics of this rare clinical entity are reviewed.

Cholesterol crystal embolism, sometimes separately designated atheroembolism, is an increasing and still underdiagnosed cause of renal dysfunction antemortem in elderly patients. Renal cholesterol crystal embolization, also known as atheroembolic renal disease, is caused by showers of cholesterol crystals from an atherosclerotic aorta that occlude small renal arteries. Although cholesterol crystal embolization can occur spontaneously, it is increasingly recognized as an iatrogenic complication from an invasive vascular procedure, such as manipulation of the aorta during angiography or vascular surgery, and after anticoagulant and fibrinolytic therapy. Cholesterol crystal embolism may give rise to different degrees of renal impairment. Some patients show only a moderate loss of renal function; in others, severe renal failure requiring dialysis ensues. An acute scenario with abrupt and sudden onset of renal failure may be observed. More frequently, a progressive loss of renal function occurs over weeks. A third clinical form of renal atheroemboli has been described, presenting as chronic, stable, and asymptomatic renal insufficiency. The renal outcome may be variable; some patients deteriorate or remain on dialysis, some improve, and some remain with chronic renal impairment. In addition to the kidneys, atheroembolization may involve the skin, gastrointestinal system, and central nervous system. Renal atheroembolic disease is a difficult and controversial diagnosis for the protean extrarenal manifestations of the disease. In the past, the diagnosis was often made postmortem. However, in the last decade, awareness of atheroembolic renal disease has improved, enabling us to make a correct premortem diagnosis in a number of patients. Correct diagnosis requires the clinician to be alert to the possibility. The typical patient is a white man aged older than 60 years with a baseline history of hypertension, smoking, and arterial disease. The presence of a classic triad characterized by a precipitating event, acute or subacute renal failure, and peripheral cholesterol crystal embolization strongly suggests the diagnosis. The confirmatory diagnosis can be made by means of biopsy of the target organs, including kidneys, skin, and the gastrointestinal system. Thus, Cinderella and her shoe now can be well matched during life. Patients with renal atheroemboli have a dismal outlook. A specific treatment is lacking. However, it is an important diagnosis to make because it may save the patient from inappropriate treatment. Finally, recent data suggest that an aggressive therapeutic approach with patient-tailored supportive measures may be associated with a favorable clinical outcome.

The incidence and prevalence of end-stage renal disease (ESRD), particularly in the elderly population, have continued to increase in the United States. It is estimated that 10% to 20% of the elderly patients with ESRD have potentially remediable renal vascular disease. The purpose of the present study is to examine the results of renal artery revascularization in 20 patients aged older than 55 years with chronic renal failure (serum creatinine level >2 mg/dL) with proximal renal artery stenosis (RAS) diagnosed by magnetic resonance angiography (MRA) who underwent surgical or percutaneous revascularization. Patients were followed up closely in the postrevascularization period; renal function was monitored and potential complications of the procedure were carefully noted. Four of the 20 patients developed serious complications, including 3 patients with clinically significant atheroembolic disease and 1 patient with renal artery dissection. Seven patients developed greater than 5% eosinophilia. Five of the 20 patients had a deterioration in renal function 3 to 6 months after the procedure, and only 5 patients had a reduction in serum creatinine concentration 3 to 6 months after the procedure. The present study suggests that in elderly patients with chronic renal failure and proximal RAS, revascularization of renal vessels is associated with a high complication rate, and improvement in renal function occurs in only 25% of the patients. Whether revascularization can slow the rate of progression of renal failure remains uncertain and can only be answered by a large prospective trial.

Renal failure is a recognized, but infrequent, complication following cardiac surgery. The causes for this condition are multifactorial, and a major concern is that the occurrence of postoperative acute renal failure is still associated with a high mortality rate.

We report unexpected acute renal failure occurring in 4 patients after uncomplicated cardiac surgery. Each patient was taking a fibric acid derivative at the time of surgery. Renal failure occurred rapidly within 3 days of surgery and was associated with increased concentrations of skeletal muscle-derived creatine kinase (CK). One patient developed myoglobinuria, and another developed a malignant hyperthermia-like syndrome.

These cases show that patients receiving lipid lowering medications could be at higher risk of developing acute renal failure after cardiac surgery. This association merits careful evaluation in large prospective studies and, if proved, would suggest that patients taking either statins or fibrates should discontinue doing so before cardiac surgery.

Renovascular hypertension represents a form of correctable hypertension and preventable renal failure. Such patients need to be identified early so that specific therapy can be instigated. Patient identification requires a high index of suspicion in patients with certain clinical features. Subsequent non-invasive imaging may result in angiography which is required for diagnostic purposes and for planning intervention. Correctable therapy takes one of two forms, namely percutaneous transluminal renal angioplasty, with or without stenting, or surgical revascularisation, together with modification of underlying risk factors.

Cholesterol crystal embolization (CCE) has been documented to affect nearly every organ system. However, CCE involving the lung is distinctly uncommon and has been documented only in the setting of an aortocaval fistula.

A case at the Massachusetts General Hospital and a MEDLINE search of English-language medical articles published between 1966 and 1997 provide the basis for this report.

The precipitants of CCE include invasive vascular procedures, anticoagulant therapy, and thrombolysis. The most common symptoms include claudication of the calf, gastrointestinal bleeding, and weight loss. The most common signs include livedo reticularis, gangrene, and ulcers. Azotemia, proteinuria, normocytic anemia, and eosinophilia often are found. Herein is described the first pathologically confirmed case of CCE to the lung in the absence of an arteriovenous fistula.

Pulmonary hemorrhage should now be included in the diverse list of presenting signs of CCE. Moreover, CCE should be considered in the differential diagnosis of pulmonary-renal syndromes.

Atheroembolic renal failure (AERF) is often seen after vascular procedures in elderly atherosclerotic patients. To estimate the incidence of AERF after coronary angiography, all patients undergoing coronary angiography at the V.A. Medical Center, Dayton, were prospectively evaluated for AERF. Since, unlike contrast nephropathy, AERF develops about a week after the vascular procedure and persists or progresses over weeks and months, serum creatinine was measured just prior to and 3 weeks after coronary angiography. Peripheral signs of cholesterol emboli were also looked for at follow-up visits. Two hundred sixty-seven patients underwent coronary angiography over a fifteen-month period. Most of the patients were sixty years old or older. Mean serum creatinine in these patients prior to coronary angiography was 1.2 mg/dL. Mean serum creatinine after coronary angiography was unchanged (1.2 mg/dL). Only 7 patients had serum creatinine > 2 mg/dL prior to coronary angiography. Two patients died within a week of coronary angiography and 2 did not return for follow-up. Of the remaining 263 patients, 5 had a serum creatinine increase by 0.5 mg/dL or more at three weeks after coronary angiography. Three of 5 had a serum creatinine increase by 1.0 mg/dL or more. Two of these 3 patients eventually died of renal failure. None of these 5 patients had peripheral signs of cholesterol emboli. In selected patients, the incidence of AERF after coronary angiography appears to be very low (< 2%).

To better characterize the heavy proteinuria occasionally described in cholesterol atheroembolic renal disease (CAE), we reviewed the clinical features and histological findings of 24 patients found at renal biopsy to have CAE. Twelve (50%) had a typical clinical presentation soon after an invasive vascular procedure. Eight (33%) underwent biopsies to evaluate proteinuria and four (17%) with insidiously developing renal failure to exclude rapidly progressive glomerulonephritis. All had usual and similar risk factors for CAE; 71% were male, 96% had peripheral vascular disease, 79% had recently undergone an invasive vascular procedure, 74% were hypercholesterolemic, and all were hypertensive. Proteinuria was higher and serum creatinine lower in the proteinuria group. In the nine (38%) nephrotic patients, serum creatinine measurements were lower (2.7 +/- 1.2 v 5.6 +/- 2.4 mg/dL), duration of renal disease to biopsy longer, and time from biopsy to dialysis greater (23.5 +/- 14.8 v 0.03 +/- 0.098 mo, P < 0.05 for all). Focal segmental glomerulosclerosis (FSGS) was observed in 15 (63%) of the biopsy specimens. Although FSGS itself did not occur more commonly in nephrotic patients, these patients did have a higher fraction of segmentally sclerosed glomeruli (0.158 +/- 0.097 v 0.026 +/- 0.050, P < 0.01). A variant of FSGS, the cellular lesion with epithelial cell prominence and capillary loop collapse, was observed in 7 of 9 (78%) patients with nephrotic-range proteinuria, but in only 3 of 12 (25%) patients with lesser degrees of protein excretion (P < 0.05). The cellular lesion was accompanied by higher mean proteinuria, 7.6 +/- 4.3 versus 2.1 +/- 2.4 g/24 hr (P < 0.01). In a larger group of patients with a similar age range as the CAE group who were identified by search of a computerized biopsy database, membranous nephropathy was the only other form of idiopathic glomerulonephritis that occurred with CAE. One of 82 (1.2%) patients with membranous nephropathy also had CAE, compared with 20 of 102 (19.6%) with FSGS (P < 0.0002, chi2). Thus, the finding of FSGS with CAE was not coincidence. Mean follow-up was 20 +/- 26 months (range, 0 to 103 months). Six patients (25%) were followed-up at least 3 years after renal biopsy. These findings indicate that extended survival in CAE is not rare and that heavy proteinuria occurs as part of a chronic disorder with distinctive histological features. Cholesterol atheroembolism with FSGS should be considered in the differential diagnosis of nephrotic syndrome in elderly patients with advanced atherosclerosis.

Cholesterol embolization (CE), usually occurring in males in their sixth or seventh decade of life, can affect multiple organ systems, including the kidney. Interventive diagnostic procedures and aortic surgery greatly increase the risk of CE. Rapid or insidious progression of renal failure in association with surgical or diagnostic radiologic procedures should suggest this diagnosis. Progressive renal insufficiency in older patients with generalized arterial disease should suggest ischemic nephropathy secondary to bilateral renal artery stenosis, renal CE, or both. Recent worsening of hypertension is characteristic of either diagnosis. A number of clinical conditions can simulate renal CE, and final differentiation may be possible only by renal biopsy. Aggressive, supportive management of renal CE is warranted because renal function may stabilize and, in a limited number of cases, may even improve.

The protean clinical manifestations of atheroembolic disease (AED) mimic systemic disorders with kidney involvement. Acute or chronic renal failure develops spontaneously or more frequently after an inciting event in patients with AED. Significant proteinuria and nephrotic syndrome, however, constitute uncommon findings. We present four patients with AED documented histopathologically who developed nephrotic-range proteinuria. The mechanisms of proteinuria are discussed, and it is suggested that AED be considered in the differential diagnosis of nephrotic syndrome in elderly patients with serious vascular disease.

Atheroembolism, caused by peripheral embolization of small cholesterol crystals that fracture off of ruptured atherosclerotic plaques in the major vessels, leads to multifocal ischemic lesions and progressive tissue loss. The end result is often ischemic injury in the skin, kidney, brain, myocardium, and intestine, but any organ distal to the culprit lesion may be affected. The precise incidence of this serious clinical syndrome has been difficult to ascertain from the available literature, but it appears to be much more common than has been assumed. The objective of the present study is to clarify the incidence of atheroembolism among inpatients in an acute hospital setting.

We surveyed inpatient nephrology consultations during a 7-month period from January through July 1994. From a pool of 402 consultation charts, 99 were identified with two or more substantive risk factors for atheroembolism. The records of 85 of these patients were available for careful review. More than 300 additional patients were found to have ICD-9 discharge codes for other vascular conditions, but we were unable to confirm that any of these were in fact cases of atheroembolism, since there is no specific ICD-9 discharge code for this entity. In the 85 cases reviewed, a diagnosis of atheroembolism was made only if the patient had identifiable substantive risk factors, suggestive physical findings, and supporting laboratory results.

Eleven of the 85 surveyed records documented strong evidence supporting a "probable" diagnosis of atheroembolism. Tissue was examined in 4 of these 11, resulting in definitive histologic confirmation in 3. Another 5 of the 85 surveyed records were "suggestive" of atheroembolism. Altogether, atheroembolism was a likely diagnosis in a total of 16 cases during this 7-month period, or 1 case in every 2 weeks. These cases comprised 19% of nephrology consultations in which 2 or more risk factors were present, or 4% or all nephrology consultations. The patients' records confirmed the serious implications of clinically detectable atheroembolism. Several patients underwent lower extremity amputation, nearly half required acute or chronic dialysis, and more than half died within several months of diagnosis

The present study suggests that at least 4% of all inpatient nephrology consultations, representing approximately 5% to 10% of the acute renal failure encountered, involve clinically significant atheroembolism. Patients with atheroembolism appear at a rate of at least 1 case every 2 weeks. They often have identifiable substantive risk factors at initial consultation, and probably represent only the most severe cases of atheroembolism. In view of the serious implications of this basically untreatable syndrome, heightened awareness and preventive maneuvers in the population at risk are essential.

The features of cholesterol crystal embolisation (CCE) to the alimentary tract were studied by retrospective analysis of the clinical and pathological data of 96 patients (70 men, 26 women, mean age 73.8 (58-95) years) with this diagnosis in the Dutch national pathology information system (Pathologisch Anatomisch Landelijk Geautomatiseerd Archief (PALGA)) from 1973-92. In the 96 patients, 130 CCE sites were found throughout the alimentary tract, mostly in the colon (42.3%). Most patients had a history of atherosclerotic disease and presented with abdominal pain, diarrhoea, or gastrointestinal bleeding, sometimes after surgical or radiological vascular procedures. A number were taking oral anticoagulant treatment. The diagnosis of CCE had been considered before the histological diagnosis in only 11 patients. In the remaining cases, ischaemic colitis, tumour, and inflammatory bowel disease were suggested in the differential diagnosis. A premortem diagnosis of CCE was made in 70.8% of the cases. In 24 of the 35 necropsy examinations, CCE seemed to be directly or indirectly related to the cause of death. It is concluded that in this unselected, homogenous group of patients, CCE sites were most frequently found in the colon. They generally presented with abdominal pain, diarrhoea, and gastrointestinal blood loss. CCE often mimicked common gastrointestinal disease, leading to incorrect diagnosis.

We report the incidence, diagnosis, prevention, and treatment of peripheral vascular complications following coronary interventional procedures as reviewed in the English-language literature. Peripheral vascular complications include hematomas, pseudoaneurysms, arteriovenous fistulae, acute arterial occlusions, cholesterol emboli, and infections that occur with an overall incidence of 1.5-9%. Major predictors of such complications following coronary interventional procedures include advanced age, repeat percutaneous transluminal coronary angioplasty, female gender, and peripheral vascular disease. Minor predictors include level of anticoagulation, use of thrombolytic agents, elevated creatinine levels, low platelet counts, longer periods of anticoagulation, and use of increased sheath size. Ultrasound-guided compression repair of pseudoaneurysms and arteriovenous fistulae are discussed, as are newer methods of treatment such as hemostatic puncture closure devices. Anticipation and early recognition of possible peripheral vascular complications in conjunction with careful attention to the optimal activated clotting time for sheath removal following coronary interventional procedures may translate into fewer vascular complications as well as into shorter and less costly hospital stays.

Atheromatous plaque material containing cholesterol crystals may dislodge and cause distal ischemia. To characterize atheroembolic renal failure, we retrospectively evaluated all patients at the Massachusetts General Hospital from 1981 to 1990 with both renal failure and histologically proven atheroembolism after angiography or cardiovascular surgery. Over the 10-year period, 52 patients were identified. They tended to be elderly men with a history of hypertension (81%), coronary artery disease (73%), peripheral vascular disease (69%), and current smoking (50%). Within 30 days of their procedure, only 50% of patients had cutaneous signs of atheroembolism, and 14% had documented blood eosinophilia. Urinalysis was often abnormal. Hemodynamically unstable patients died shortly after their procedure, yet renal function in the remainder continued to decline over 3 to 8 weeks. Patients who received dialysis had a higher baseline serum creatinine than those who did not (168 +/- 44 mumol/L versus 133 +/- 18 mumol/L, p = 0.02), with dialysis starting a median of 29 days after the procedure. Patients with renal failure due to atheroembolism alone, as opposed to multiple renal insults, were more likely to recover renal function (24% versus 3%, p = 0.03) and had a lower risk of death during the 6 months after their procedure (log-rank p = 0.002). Renal failure due to procedure-induced AE is characterized by a decline in renal function over 3 to 8 weeks. This time course is not consistent with most other iatrogenic causes of renal failure, such as radiocontrast or nephrotoxic medications, which present earlier and often resolve within 2 to 3 weeks after appropriate intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal angiography remains the "gold standard" procedure for the detection of renal artery stenosis. However, clinicians often avoid renal angiography because of fears of contrast media-associated nephrotoxicity (CM-AN) and atheroembolism. This review focuses on these potential angiographic complications, with particular emphasis, in the case of CM-AN, on clinical features, incidence, risk factors with an emphasis on pre-existing renal insufficiency and diabetes mellitus, volume of contrast media, low osmolar versus high osmolar contrast media, and prophylaxis. For atheroembolism, areas emphasized are pathology, clinical features, precipitating features, and incidence in various settings. Although the literature contains an abundance of information about CM-AN and atheroembolism, this review identified multiple areas of uncertainty regarding features of both of these complications. For example, additional studies are needed to determine the incidence of CM-AN, both asymptomatic and clinically severe, in patients with a wide range of pre-existing renal insufficiency with and without diabetes mellitus, following low volume digital subtraction renal angiography with low osmolar contrast media. In a similar manner, studies are needed with adequate postcontrast observation periods to determine the true incidence of clinically significant atheroembolism following diagnostic renal angiography and angioplasty and techniques that may modify this complication. Until further knowledge in both of these areas is available, it is difficult to precisely determine the risks of renal angiography and/or angioplasty in the azotemic patient suspected of or having renal ischemic disease using modern radiologic techniques.

We evaluated two patients with systemic cholesterol embolization (SCE) associated with the development of pleural effusions. These two patients had evidence of atherosclerosis and presented with livedo reticularis, renal insufficiency, and gangrenous cutaneous changes as manifestations of their SCE. In both cases, closed pleural biopsies demonstrated acute inflammation of the parietal pleura. Our experience with these individuals and a review of the medical literature suggest that pleural injury from atheromatous embolization may occur. Physicians caring for patients with SCE should be aware of the possible association of pleural reactions with this process.

Eosinophiluria has been reported in acute interstitial nephritis and other renal diseases, but its presence in atheroembolic renal disease (AERD) has not been previously established. AERD has been identified as a cause of acute and chronic renal failure, particularly in elderly patients with advanced atherosclerosis and in those patients who have undergone manipulation or intervention of the abdominal aorta, renal artery, or coronary artery. The definitive diagnosis is made by renal biopsy. However, many patients are too acutely ill to tolerate renal biopsy and, in recent years, peripheral eosinophilia, hypocomplementemia, and thrombocytopenia have been recognized in association with AERD. Previous studies have reported that AERD is associated with an inactive renal sediment and an absence of urine eosinophils. We reviewed our experience over a 4-year period with 24 patients with renal biopsy-proven AERD.

Urine eosinophils were evaluated in nine patients to help determine the cause of their renal deterioration. Seven of these patients presented with evidence of vascular disease. Three patients had procedures involving manipulation of the abdominal aorta. Physical examination revealed findings of atheroembolism in three of nine patients. Overall, eight of nine patients had a positive Hansel's stain for eosinophiluria. Six of eight patients had more than 5% of their urinary white cell count as eosinophils. The reason for failure of previous studies to detect eosinophiluria in AERD is unclear but may have been related to the use of Wright's stain instead of Hansel's stain.

In the evaluation of acute renal insufficiency, eosinophiluria may indicate AERD in addition to the other known causes for this finding.

Atherosclerotic vascular disease can give rise to provoked or spontaneous cholesterol crystal embolization to organ systems. Lodging in downstream arterioles, these crystals can produce granuloma formation, infarction, ulceration, and perforation. Histologic sections of the tissue concerned invariably show pathognomonic empty needle-shaped clefts left by the crystals after processing of the material. In the digestive system these events can cascade to many and often misleading presentations. They can be the cause of massive bleeding, acute acalculous cholecystitis, pancreatitis, or teleangiectasis with chronic intractable blood loss. Owing to the progressive nature of the disease the treatment options described in this paper can only give temporary, but nevertheless often worthwhile relief.

Although a wide variety of disease processes can result in a failure of renal excretory function, the vast majority of cases with "acute renal failure" (ARF) are due to the syndrome of acute tubular necrosis (ATN). The syndrome is usually initiated by an acute injury to the proximal renal tubular epithelial cells by ischemic or nephrotoxic events. This is followed by progressive and often rapid increases in the concentration of blood urea nitrogen (BUN) and serum creatinine. In the average case, the failure of renal excretory function persists for 1 to 3 weeks, to be followed by recovery. Oliguria (urine volume less than 400 ml) is present in about half of the patients. The pathogenesis of the retention of nitrogenous waste in human ATN is the subject of controversy, but the balance of data in most patients suggests that the predominant mechanism is a profound secondary vasoconstriction in response to tubular cell injury. This may represent a teleologically appropriate response to prevent catastrophic losses of fluid that would occur, if the normally high rates of glomerular filtration continued, in the face of reduced tubular reabsorptive capacity. The mechanisms by which the tubular cell injury is communicated to the vasculature, and the mediators of the hemodynamic changes, remain to be established. The differential diagnosis in a patient with ARF, usually involves exclusion of an obstruction to the urinary tract as an initial step. The next step is to differentiate the patients with ATN from those who have renal hypoperfusion in response to events in the systemic circulation, but who otherwise have functionally and structurally intact kidneys, i.e., prerenal ARF. The kidneys of patients with prerenal ARF exhibit the normal renal response to an acute reduction in renal blood flow and glomerular filtration rate (GFR). This consists of avid reabsorption of the filtered salt and H2O, so that a small amount of concentrated and NaCl-poor urine is elaborated. The tubular cell injury in ATN syndromes prevents this response from maximally occurring, so that the urine is isosmotic and relatively rich in NaCl.