Proportion and risk factors of cholesterol crystal embolization after cardiovascular procedures: a retrospective national database study.

Cholesterol crystal embolization (CCE) is a rare, mainly iatrogenic condition. The proportion of CCE after cardiovascular procedures has not been fully elucidated. The purpose of this study was to determine the proportion of CCE diagnosed after cardiovascular procedures and to identify risk factors for CCE occurrence. Data on patients aged older than 40 years who underwent cardiovascular procedures between July 2010 and March 2017 were extracted from the Japanese Diagnosis Procedure Combination database. Inpatients diagnosed with CCE within 1 year after procedures in the same hospital were identified. Logistic regression analysis was performed to identify factors associated with the occurrence of CCE. There were 962 patients with CCE in 2,190,300 patients who underwent cardiovascular procedures. The overall proportion of CCE after cardiovascular procedures was 4.4 per 10,000 patients (95% confidence interval 4.1-4.7). The overall in-hospital mortality among patients with CCE was 11% (107/962). Older age, male sex, smoking, heart failure, peripheral vascular disease, cerebrovascular disease, renal insufficiency, diabetes mellitus, hypertension, and aortic aneurism and dissection were significantly associated with the higher occurrence of CCE. Compared with cardioangiography, several procedures were significantly associated with higher occurrence of CCE, including intra-aortic balloon pumping, percutaneous transluminal angioplasty of the renal artery, and transcatheter aortic valve implantation or balloon aortic valvuloplasty. CCE is rare but remains a severe complication of cardiovascular procedures. Atherosclerotic risk factors and certain cardiovascular procedures were associated with CCE.

Cholesterol embolization syndrome: An under-recognized entity in cardiovascular interventions.

Cholesterol embolization syndrome (CES) is a multi-systemic disease caused by embolization of atherosclerotic plaque contents from proximal large-caliber artery to distal small to medium arteries, occurring spontaneously or more commonly after vascular intervention. This report is a comprehensive review of the reported cases of CES found in our literature search. We discuss the risk factors, clinical manifestations, management, and prognosis of CES. The major predisposing factors for CES include older age, male sex, atherosclerotic cardiovascular risk factors, anticoagulation, and femoral access route. The composite incidence of atheroembolic renal disease was 92% and mortality 63%. Our review highlights the importance to recognize this disease entity for the cardiologist and nephrologist.

Association between absolute blood eosinophil count and CKD stages among cardiac patients.

Elevated eosinophil count was shown to be associated with the development of cholesterol embolization syndrome, a potentially life-threatening condition, after catheter-based procedures. We investigated the association between stages of chronic kidney disease (CKD) and the absolute eosinophil count (AEC) among cardiac patients. CKD stages were determined solely on the estimated glomerular filtration rate or requirement for hemodialysis. Eosinophilia is defined as an eosinophil count exceeding 500/µL. A total of 1022 patients were enrolled in the current study, and eosinophil counts (/µL) in the first through fourth eosinophil count quartiles were <88, 88 to 154, 155 to <238, and 238 ≤, respectively, and 29 patients (2.8 %) had eosinophilia. Correlation coefficient between the AEC and age was -0.188 (P = 0.001) in women and -0.042 (n.s.) in men (by Spearman's correlation test). Patients with higher CKD stages had a higher prevalence of the highest AEC quartile or eosinophilia. Logistic regression analysis using severe renal dysfunction (i.e., CKD stage 4 or 5) as the dependent variable, the highest AEC quartile had a significant positive association with an odds ratio of 1.99 (95 % confidence interval, 1.20-3.31, P < 0.01) after adjustment for sex, age, systolic blood pressure, and total white blood cell count. Similarly, after adjustment for the same variables, eosinophilia was associated with severe renal dysfunction with an odds ratio of 2.60 (95 % confidence interval, 1.08-6.26, P < 0.05). Eosinophil count was positively associated with higher CKD stages among cardiology patients, some fraction of which might be related to subclinical cholesterol embolization.

Incidence, Risk Factors, and Prognosis of Cholesterol Crystal Embolism Because of Percutaneous Coronary Intervention.

Cholesterol crystal embolism (CCE) is a rare but serious complication of percutaneous coronary intervention (PCI). However, its incidence, risk factors, and prognosis in the contemporary era are not well known. We included 23,184 patients who underwent PCI in our institution between January 2000 and December 2019 in this study. The diagnosis of CCE was made histologically or by the combination of cutaneous signs and specific blood test results. In patients with CCE, we evaluated the incidence, risk factors, and prognosis. A total of 88 patients (0.38%) were diagnosed with CCE. The incidence of CCE seemed to decline through the investigated 20 years. Positive predictors of CCE were age ≥70 years (68% vs 59%, p = 0.012), aortic aneurysm (23% vs 7.2% p <0.001), and a femoral approach (71% vs 45%, p <0.001), whereas a negative predictor of CCE was the use of an inner sheath (63% vs 77%, p <0.001). The rate of 1-year mortality and the requirement for chronic hemodialysis within 1 year after PCI in patients with CCE were 10% and 11%, respectively. The use of an inner sheath and a nonfemoral approach was associated with a lower incidence of CCE. In conclusion, because the prognosis of patients with CCE is still poor, preprocedural identification of high-risk patients and selection of low-risk procedures could be important for preventing CCE.

Combined assessment of carotid vulnerable plaque, renal insufficiency, eosinophilia, and hs-CRP for predicting risky aortic plaque of cholesterol crystal embolism.

BACKGROUND: Cholesterol crystal embolism (CCE) is a serious complication of vascular procedures and based on the clinical features of patients with CCE, the aim of the present study was to establish screening criteria for aortic complex plaques (ACP) at high-risk of CCE. METHODS AND RESULTS: For the first study, 10 patients diagnosed as having CCE were recruited. They had prior multiple atherosclerotic disease and a high proportion of complex plaques of the carotid artery and aorta. Elevated levels of high-sensitivity C-reactive protein (hs-CRP), eosinophilia, and renal insufficiency were already recognized before CCE diagnosis. The second study prospectively enrolled 102 patients. ACP is related to CCE and predictive criteria of ACP were established. Among 19 patients with ACP, 2 presented with CCE. Multivariate analysis revealed carotid complex plaque, eosinophilia and multiple atherosclerotic risk factors as independent predictors of ACP. The criteria including these factors (multiple atherosclerotic risk factors, carotid complex plaque, hs-CRP > or =0.2 mg/dl, eGFR < or =60 ml . min(-1) . 1.73 m(-2), eosinophil count > or =400 /microl) could detect patients with ACP with 95% sensitivity, 94% specificity, and 79% positive predictive value. CONCLUSIONS: Multiple atherosclerotic risk factors, elevated hs-CRP, renal insufficiency, eosinophilia before CCE diagnosis and carotid complex plaques were features of patients with CCE. Diagnostic criteria including these characteristics effectively predict ACP patients at high-risk of CCE. (Circ J 2010; 74: 51 - 58).

[Atheroembolic renal disease: analysis of clinical and therapeutic factors that influence its progression]. / Enfermedad renal ateroembólica: un análisis de los factores clínicos y terapéuticos que influyen en su evolución.

Cholesterol embolism is a disease caused by distal showering of cholesterol crystal released from disintegration of arterial atheromatous plaques. It may occur spontaneously or more often after invasive vascular procedures or thrombolytic/anticoagulant agents. Forty five cases were diagnosed between 1989 and 2005 in three Spanish hospitals. The diagnosis was confirmed by histology or diagnostic ophthalmoscopic findings. The majority were male (93.3%), elder (55.5% were older than 70 years), smoker (91.1%), had hypertension (95.6%), with high prevalence of cardiovascular risk factors. At the time of diagnosis all patients presented acute renal failure. Mean serum creatinine at diagnosis was 4.3+/- 2.4 mg/dl. The acute renal failure was accompanied with eosinophilia (64.4%) and cutanous lesions (57.7%). 20% of cases occur spontaneously and 46.7% after endovascular manipulation (coronary angiography/arteriography) and only 8% after changes in anticoagulant treatment. After a follow-up of 12 +/- 16.3 months the 55.6% of patients need chronic dialysis, 64.4% died, 8 of them after the beginning of dialysis. Nine patients recovered renal function, with a mean creatinine of 3 +/- 1.7 mg/dl at the end of follow-up. The cardiovascular comorbididy and the clinical severity of the embolism don t have impact in the renal or patient survival. Renal survival (Kaplan-Mier) were better in spontaneous than in iatrogenic cholesterol embolism. Fifteen of 45 patients were treated with steroids. In treated patients we observed a high incidence of death (73.3% versus 60%) and fewer recovery of renal function (13.3% versus 23%), without statistical significance. The mean time to dialysis was shorter in treatment patients (p= 0.017). Statins treatment was not associated with outcome (renal or individual). In summary, atheroembolic renal disease represents an acute renal failure with special characteristics. Renal and individual outcome is poor, but some patients have spontaneous recovery of renal function. Renal survival was significantly better in spontaneous disease. We don t observe beneficial effect of steroid treatment.

Better With Ultrasound: Arterial Line Placement.

Arterial catheterization is frequently performed in ICUs to facilitate hemodynamic monitoring and frequent blood sampling. Overall, arterial catheterization has high success and low complication rates, but in patients who are critically ill, the incidence of failure is higher because of hypotension, peripheral edema, and obesity. Ultrasound guidance significantly increases the likelihood of successful cannulation and decreases complications compared with traditional landmark-based techniques. Multiple ultrasound techniques for radial and femoral arterial catheter insertion have been described; this paper presents an approach for incorporating these tools into bedside practice, including illustrative figures and narrated video presentations to demonstrate the techniques described.

[Update on cholesterol crystal embolism]. / État des lieux de la maladie des emboles de cholestérol.

Cholesterol crystal embolism is a systemic pathology associated with diffuse atherosclerosis. Pathophysiology corresponds to tissue necro-inflammation secondary to arteriolar occlusion associated with microembolism from atherosclerotic plaques of large diameter arteries. The clinical presentation is heterogeneous and polymorphic. Multiple organs may be the targets, but preferential damage is skin, kidneys and digestive system. It is a serious pathology, underdiagnosed, with a poor prognosis. The risk factors for developing the disease remain the same risk factors as atheroma. The factors favouring migration of microembolism remain mainly vascular interventional procedures; easy to diagnose, they oppose spontaneous embolic migrations or secondary to the introduction of antithrombotic treatment, whose diagnosis is more difficult and the prognosis more severe. The diagnosis of the disease remains mostly a diagnosis of elimination and often refers to a bundle of clinical, biological, morphological and histologic arguments. The treatment is poorly codified and the subject of few publications. It will favour both symptomatic treatment (and mainly that of pain) and complications (high blood pressure, renal insufficiency). The aetiological support remains less consensual. The treatment of atherosclerotic plaques consists, of course, in the correction of classical cardiovascular risk factors, the introduction of a statin. It will be discussed in the implementation of surgery or angioplasty to exclude potentially responsible atherosclerotic lesions. Eviction of antithrombotic therapy should be considered in terms of the benefit-risk balance, but often in favour of maintaining it. Finally, other treatments may be proposed in a case-by-case basis, such as oral or intravenous corticosteroid therapy, colchicine or LDL aphaeresis.

Renal function, atherothrombosis extent, and outcomes in high-risk patients.

BACKGROUND: Although prior data showed an association between chronic kidney disease (CKD) and atherothrombotic events, little is known about the risk profile and specific outcomes of atherothrombotic outpatients with CKD. METHODS: More than 69,000 outpatients at risk of atherothrombotic events were enrolled in the REACH Registry. Creatinine clearance (CrCl) was available for 51,208 patients divided into 4 groups: normal (CrCl > or =90 mL/min, n = 13,949), mild (60-89 mL/min, n = 19,474), moderate (30-59 mL/min, n = 15,883), and severe CKD (CrCl <30 mL/min, n = 1902). Baseline characteristics, number of arterial beds overtly affected, medications, overall mortality, cardiovascular death, myocardial infarction, stroke, congestive heart failure, peripheral arterial events, and bleeding events were assessed according to renal function. RESULTS: The number of arterial beds affected increased with severity of CKD. However, patients with severe CKD were less likely to receive medications of proven benefit. Severe CKD was an independent correlate of all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, peripheral arterial revascularization, or amputation. CONCLUSION: One third of outpatients at risk for atherothrombotic events have moderate to severe CKD. They are less likely to receive beneficial therapies despite a higher atherothrombotic burden and worse outcomes.

Cholesterol-embolization syndrome: current perspectives.

Cholesterol-embolization syndrome (CES) is a multisystemic disease with various clinical manifestations. CES is caused by embolization of cholesterol crystals (CCs) from atherosclerotic plaques located in the major arteries, and is induced mostly iatrogenically by interventional and surgical procedures; however, it may also occur spontaneously. Embolized CCs lead to both ischemic and inflammatory damage to the target organ. Therefore, anti-inflammatory agents, such as corticosteroids and cyclophosphamide, have been investigated as treatment for CES in several studies, with conflicting results. Recent research has revealed that CES is actually a kind of autoinflammatory disease in which inflammasome pathways, such as NLRP3 and IL1, are induced by CCs. These recent findings may have clinical implications such that colchicine and IL1 inhibitors, namely canakinumab, may be beneficial in the early stages of CES.

[Kidney disease care for the elderly]. / Spécificités des néphropathies du sujet âgé.

In our aging population, kidney disease management needs to take into account the frailty of the elderly. Standardized geriatric assessments can be proposed to help clinicians apprehend this dimension in their daily practice. These tools allow to better identify frail patients and offer them more personalized and harmless treatments. This article aims to focus on the kidney diseases commonly observed in elderly patients and analyze their specific nephrogeriatric care modalities. It should be noticed that all known kidney diseases can be also observed in the elderly, most often with a quite similar clinical presentation. This review is thus focused on the diseases most frequently and most specifically observed in elderly patients (except for monoclonal gammopathy associated nephropathies, out of the scope of this work), as well as the peculiarities of old age nephrological care.

Case Report: Atheroembolic renal disease in a 72-year-old patient through coronary intervention after myocardial infarction.

Cholesterol embolization or atheroembolic renal disease (AERD) is an often underdiagnosed issue in patients featuring a prevalent risk profile. It is a multisystemic disease with progressive renal insufficiency due to foreign body reaction of cholesterol crystals flushed into a small vessel system of the kidneys from the arteriosclerotic plaques. The most common setting in which it occurs is iatrogenic after vascular catheterization and less frequent spontaneously. Typical clinical symptoms are delayed impairment of renal function, cutaneous manifestations such as livedo reticularis or purple toes with persistingly palpable arterial pulse, myalgia, systemic symptoms such as weight loss and fever, and abdominal and neurological symptoms. Diagnosis is generally made by clinical appearance, risk profile, and interval of time from intervention; a definitive diagnosis can only be made by renal biopsy. Even though the exact incidence is not known because most patients do not undergo biopsy due to older age, comorbidity, and other explanations for loss of renal function, it is estimated to be 4% after vascular intervention. Patient and renal outcome is dependent on comorbidity, risk profile, and preexisting chronic kidney disease (CKD). About 30% of patients are estimated to require maintenance dialysis and these patients have a high risk of death within 24 months after the first renal replacement therapy. Prognosis is also influenced by severity. The case reported is a 72-year-old male patient with preexisting CKD stage 3 undergoing percutaneous coronary intervention after myocardial infarction and consecutive AERD with typical clinical appearance 6 weeks after the event.

Cholesterol embolization in renal allografts: a clinicopathologic study of 12 cases.

Cholesterol embolization (CE) in renal allografts is a rare occurrence, the natural history and prognostic significance of which is poorly characterized. We studied the clinicopathologic features and outcome of the largest known series of CE in renal allografts and combined our cases with those in the literature. We identified renal allograft biopsies with CE from 1997 to September 2004 at University of Pittsburgh Medical Center (UPMC). All pathology material related to such biopsies were examined and correlated with clinical information to determine the most probable CE source. Among 5435 RAB, 19 from 12 cadaveric transplant recipients comprising 7 males and 5 females (median age=63 y) had CE. Donors consisted of 9 males and 2 females (median age=47 y). One donor's age and sex was unknown. The most probable CE source was recipient in 9 cases and donor in 3 cases. Five had acute renal failure without acute cellular rejection and 2 had CE-specific failed allografts. Of 19 RAB, the most frequent coexisting diagnosis was chronic allograft nephropathy (63%). The median follow-up time was 661 days. Combining UPMC and non-UPMC cases (n=37) revealed a statistically significant loss of grafts with donor-derived (P value=0.00459) and early CE (P value=0.00938). In renal allografts, CE most often correlated with recipient and donor atherosclerosis. It may present with acute renal failure, but usually not acute graft loss. Graft failure is significantly associated with donor-derived and early CE. Although its prognosis may be poor in the setting of primary nonfunction, prolonged graft survival may be seen.

The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study.

BACKGROUND: Cholesterol embolization syndrome is a systemic disease caused by distal showering of cholesterol crystals after angiography, major vessel surgery, or thrombolysis. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Cholesterol crystal embolization in the Netherlands.

OBJECTIVE: To clarify the incidence and clinical features of cholesterol crystal embolization (CCE). METHODS: Analysis of the relevant data of 842 diagnosed cases of CCE filed in the Dutch National Pathology Information System from 1973 through 1994. RESULTS: No report of CCE was recorded from 1973 through 1979. Since then, its incidence rose from 0.9 case per million population in 1980 to 6.0 cases per million population in 1985, but stabilized thereafter. Among autopsy reports, the relative percentage of CCE was similar over the years, with 0.35% in 1982 and 0.30% in 1994 (mean 0.31% range, 0.20% to 0.42%). Nine patients in whom CCE was found in their renal transplant were excluded from the study. Thus, among a total of 833 elderly (mean age, 72.1 years), predominantly male (73.9%) patients, 1066 CCE sites were found in 323 biopsy reports, 264 resection reports, and 287 autopsy reports. CONCLUSION: In the Dutch population, CCE is reported steadily, with an average frequency of 6.2 cases per million population per year since 1985. It occurs predominantly in elderly men with a history of atherosclerotic disease and hypertension. Symptoms may be absent, go unrecognized, or mimic other disease processes. It can also be a coincidental finding. The primary CCE site is the kidney, followed by the skin and gastrointestinal tract.

Cholesterol embolization treated with corticosteroids--two case reports.

Cholesterol embolization (CE) is a potentially serious complication associated with invasive arterial maneuvers, in which standard therapy has not been established. We experienced two cases of CE in patients with severe atherosclerosis whose renal function deteriorated within a few months after invasive arterial maneuvers. CE was confirmed either by renal biopsy (case 1) or skin biopsy (case 2). Oral administration of prednisolone at a daily dose of 30 mg (0.4 mg/kg) was effective to improve their renal function. Our observation suggests that corticosteroid therapy may be beneficial in some patients with CE.

Hyperhomocysteinemia and traditional cardiovascular disease risk factors in end-stage renal disease patients on dialysis: a case-control study.

Hyperhomocysteinemia occurs frequently in end-stage renal disease (ESRD), but its prevalence in comparison with traditional cardiovascular disease (CVD) risk factors is unknown. Fasting total plasma homocysteine, potential determinants of plasma homocysteine (i.e., plasma B-vitamins and serine), total and HDL cholesterol, glucose, and creatinine, were determined in 24 ESRD patients on dialysis, and 24 age, gender, and race matched Framingham Offspring Study controls with normal renal function. Presence of clinical CVD and CVD risk factors was established by standardized methods. Mean plasma homocysteine was markedly higher in the ESRD patients versus controls (22.7 vs. 9.5 mumol/l). ESRD patients were 33 times more likely than controls to have hyperhomocysteinemia (> 15.8 mumol/l) (95% confidence interval, 5.7-189.6). Hyperhomocysteinemia persisted in the ESRD patients despite normal to supernormal B-vitamin status. Plasma serine levels below the tenth percentile of the control distribution were found in 75% of the ESRD patients. Oral serine supplementation caused a 37% increase in mean plasma serine, but had no effect on plasma homocysteine in four ESRD patients with supernormal plasma folate, low plasma serine, and hyperhomocysteinemia. Given its unusually high prevalence, improved management of hyperhomocysteinemia might reduce CVD sequelae in ESRD.

Redefining the incidence of clinically detectable atheroembolism.

BACKGROUND AND OBJECTIVES: 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. PATIENTS AND METHODS: 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. 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 CONCLUSIONS: 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.

Cholesterol embolization in renal allografts.

Renal cholesterol embolization (RCE) in native kidneys has a dismal outcome and frequently leads to irreversible renal failure. RCE may rarely occur in renal allografts as well, particularly if the recipient or the donor has prominent atherosclerosis. The natural history of RCE in renal transplants is unknown. We have reviewed the surgical pathology files of The Johns Hopkins Hospital in the 14-year period between 1984 and early 1999 and found 7 RCE cases among 1500 renal transplant biopsies (0.47%). One of the seven cases had three biopsies showing cholesterol emboli, the first of which was a postreperfusion (immediate posttransplant) biopsy. The probable source of the cholesterol emboli was the recipient in six cases and the donor in one case. Five donors were cadaveric and two were living donors. Six biopsies were taken within the first 4 months posttransplant (four were postreperfusion biopsies). One recent patient had the inciting event of arteriography and stent placement 2 years posttransplant and is currently doing well. One kidney failed due to posttransplant lymphoproliferative disorder (PTLD), another kidney failed with complicating opportunistic infections, and the other five were functioning 2 to 6 years posttransplant. A literature review revealed additional 14 RCE cases in renal transplants. Combining our cases with those in the literature (21 cases), reveals that the origin of the RCE was probably the recipient in 11 cases (seven cadaveric, two living-related, and two unknown), and the donor in 10 cases (eight cadaveric and two unknown). Graft failure occurred in two of the 11 cases, where RCE was of probable recipient origin. Seven of the 10 kidneys, where the RCE was probably of donor origin, failed due to allograft dysfunction; one of them also developed superimposed rejection and cytomegalovirus infection. We conclude that if RCE is originating in the recipient, graft survival is usually good. In contrast, if RCE is of donor origin, graft dysfunction and subsequent graft loss are common. The reason for this difference may be the more extensive RCE developing in an atherosclerotic cadaveric donor during organ procurement or severe trauma leading to death.

Effects of hormone replacement therapy on the circadian pattern of atherothrombotic risk factors.

Onset of acute atherothrombotic events (acute myocardial infarction, unstable angina, ischemic stroke) exhibit a circadian pattern that parallels the diurnal pattern of endogenous fibrinolytic activity. Hormone replacement therapy in postmenopausal women has been shown to enhance fibrinolytic capacity by lowering plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator inhibitor (tPA) antigen values. We evaluated the impact of 4 weeks of estrogen alone (Premarin 0.625 mg/day) and 2 weeks of estrogen plus progesterone (Provera 2.5 mg/day) on PAI-1 and tPA in 17 postmenopausal women at multiple time points to assess hormone impact on the diurnal pattern of fibrinolytic potential. At baseline, both PAI-1 and tPA exhibited circadian variability. Estrogen alone selectively lowered 8 A.M. PAI-1 (35.8 +/- 7.1 ng/ml at baseline, 19.8 +/- 3.7 ng/ml on estrogen; p = 0.0002 vs baseline). There was no significant change in the noon or 4 P.M. values, and the diurnal pattern was attenuated. The 8 A.M. PAI-1 remained low at 17.1 +/- 3.6 ng/ml (p = 0.0001 vs baseline) with total loss of the circadian rhythm. Estrogen supplementation reduced tPA antigen at all time points, and the diurnal pattern, although blunted, persisted. Addition of progesterone to estrogen did not reverse effects of the estrogen alone phase of either PAI-1 or tPA values. This hormone-associated reduction of PAI-1 was observed despite increased triglycerides, a known inducer of PAI-1 levels. These observations suggest that hormone replacement therapy may protect postmenopausal women from excess early morning acute ischemic events.