Both hyperglycemia and hyperuricemia aggravate acute kidney injury during cholesterol embolism syndrome despite opposite effects on kidney infarct size.

Kidney cholesterol crystal embolism (CCE) occurs in advanced atherosclerosis and induces a thrombotic (micro)angiopathy, a drop in the glomerular filtration rate (GFR), and an ischemic kidney infarction with necroinflammation. We speculated that common metabolic comorbidities such as diabetes or hyperuricemia would independently modulate each of these distinct pathophysiological processes. To test this, experimental CCE was induced by injecting cholesterol crystals into the left kidney artery of mice and thrombotic angiopathy, GFR drop, and infarct size were analyzed after 24 hours in the presence of hyperglycemia (about 500 mg/dL) or hyperuricemia (about 8 mg/dL) or their absence. In healthy mice, unilateral CCE caused diffuse thrombotic angiopathy in interlobar, arcuate and interlobular arteries, followed by a 50% or less drop in GFR compared to baseline and a variable degree of ischemic kidney necrosis. Hyperglycemia but not hyperuricemia aggravated thrombotic angiopathy although both caused a GFR decline, albeit via different mechanisms. Hyperglycemia aggravated GFR loss by increasing necroinflammation and infarct size, while the antioxidative effects of hyperuricemia reasonably attenuated necroinflammation and infarct size but induced a diffuse vasoconstriction in affected and unaffected kidney tissue. Thus, both hyperglycemia or hyperuricemia aggravate CCE-induced acute kidney failure despite having opposite effects on ischemic necroinflammation and infarction.

The systemic immune response due to cholesterol crystal embolization syndrome: a case report.

BACKGROUND: Cholesterol crystal embolization syndrome (CES) occurs when an atherosclerotic plaque causes small-vessel embolization, resulting in multi-organ damage. Although CES is pathologically characterized by an infiltration of eosinophils, the implication of the systemic inflammatory response represented by hypereosinophilia is unclear in clinical practice. Herein we present the case of a patient diagnosed with CES who developed multiple allergic organ injuries, including daptomycin-related dermatitis and later vancomycin-induced acute tubulointerstitial nephritis, which was successfully treated by the withdrawal of each medicine with or without corticosteroid therapy, one by one. CASE PRESENTATION: A 76-year-old Japanese man diagnosed with thoracic aneurysm rupture underwent total arch replacement through the open stent graft technique. Postoperatively, he developed methicillin-resistant Staphylococcus epidermidis bacteremia, which was treated with daptomycin. Subsequently, he presented with palpable purpura on both dorsal feet, erythema around his body, and hypereosinophilia. Daptomycin was replaced with vancomycin due to suspicion of drug-induced erythema. The erythema gradually faded. On nine days after vancomycin therapy, the systemic erythema rapidly reappeared followed by acute renal failure. The renal function decline prompted hemodialysis. A skin biopsy revealed cholesterol embolization, whereas a kidney biopsy revealed acute tubulointerstitial nephritis. After vancomycin discontinuation and initiation of systemic corticosteroid treatment, his kidney function was restored to the baseline level. CONCLUSIONS: The present case highlights cholesterol embolization can cause allergic complications in addition to direct organ damage.

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.

[Atheroembolic renal disease: risk factors, diagnostics, histology, and therapeutic approaches].

The increase in patients' average age, the enhancement of anticoagulation therapy and the growth of vascular interventions represent the perfect conditions for the onset of atheroembolic renal disease. AERD is observed in patients with diffuse atherosclerosis, generally after a triggering event such as surgery on the aorta, invasive procedures (angiography, catheterization of the left ventricle, coronary angioplasty) and anticoagulant or fibrinolytic therapy. The clinical signs are heterogeneous, a consequence of the occlusion of downstream small arterial vessels by cholesterol emboli coming from atheromatous plaques of the aorta, or one of its main branches. The proximity of the kidneys to the abdominal aorta, and the high flow of blood they receive, make them a major target organ. For this reason, AERD represents a pathological condition that always needs to be taken into account in the nephropathic patient, although its systemic nature makes the diagnosis difficult. This manuscript presents a review of the existing literature on this pathology, to provide an updated summary of the state of the art: risk factors, diagnostics, histology and therapeutic approaches.

A case of cholesterol embolization syndrome mimicking rapidly progressive renal failure causing end-stage kidney disease.

Cholesterol embolization syndrome is an uncommon complication of coronary angioplasty. Its clinical manifestations are nonspecific and may be ascribed to other causes mimicking vasculitis syndrome. In an appropriate clinical setting, the diagnosis can be confirmed by tissue biopsy. In this case report, we present a middle-aged male who presented with cutaneous and renal manifestations within two weeks of primary angioplasty. The patient had progressive clinical deterioration in the form of dry gangrene of toes and end-stage renal disease requiring surgical amputation and maintenance hemodialysis respectively within two months of symptoms onset.

An Autopsy Case of Acute Pancreatitis Caused by Cholesterol Crystal Embolization.

Cholesterol crystal embolization (CCE) shows a poor prognosis and it can cause ischemic organ damage due to a cholesterol embolism from atherosclerotic lesions in large blood vessels. Such an embolism mainly affects the kidneys and skin, although cases involving digestive organs have also been reported. We encountered an autopsy case of CCE with damage mainly to the digestive organs, including the pancreas. The patient had non-specific abdominal symptoms or image findings. Symptomatic therapy failed to save him. CCE can involve the digestive organs, and so must be differentiated from abdominal pathologies. Moreover, conventional treatments may be ineffective, and new treatments might thus be necessary.

50-year-old man • foot pain • "purple" toe • history of smoking • Dx?

► Foot pain ► "Purple" toe ► History of smoking.

Cholesterol Emboli Co-Existing with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in a 76-Year-Old Woman.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis injures small vessels and causes severe systemic organ injury. Main target antigens of ANCA are myeloperoxidase and proteinase 3. ANCA strongly associates with the development and progression of the vasculitis. Its manifestations include rapidly progressive glomerulonephritis, interstitial pneumonitis, alveolar hemorrhage, purpura, and neurological disorder. Most patients with ANCA-associated vasculitis in Japan are elderly and have atherosclerotic risk factors. Cholesterol emboli are systemic vascular inflammation triggered by cholesterol crystals. Cholesterol emboli cause kidney dysfunction and ischemia of the intestines, brain, heart, skin, and peripheral nerves. Diabetes mellitus, hypertension, hyperlipidemia, and history of cardiovascular diseases are risk factors of the development of cholesterol emboli. We report a case of ANCA-associated vasculitis coexisting with cholesterol emboli. A 76-year-old woman was diagnosed with ANCA-associated interstitial pneumonitis. She rapidly developed progressive glomerulonephritis, purpura, and peripheral sensory nerve disorder. A kidney biopsy revealed that renal dysfunction was caused by vasculitis of the interlobular arteries and cholesterol emboli. A skin biopsy revealed that purpura was caused by cholesterol emboli. Glucocorticoid and statin therapies were administered. Thereafter, the renal function and other symptoms improved and stabilized. The representative symptoms of ANCA-associated vasculitis and cholesterol emboli are closely similar, and it is difficult to distinguish between these diseases when they coexist. Because the background characteristics of patients with ANCA-associated vasculitis and risk factors of cholesterol emboli overlap, at the time of diagnosing ANCA-associated vasculitis, clinicians should consider the possibility of cholesterol emboli coexistence.

Association between eosinophilia and renal prognosis in patients with pathologically proven cholesterol crystal embolism.

BACKGROUND: Approximately, 20-70% of patients with cholesterol crystal embolism (CCE) have eosinophilia. However, it remains unknown how eosinophilia influences renal prognosis in patients with CCE. In this study, we investigated the association between eosinophil count (Eo) and renal prognosis in CCE patients on steroid therapy. METHODS: The present study is a single-centered retrospective cohort study in patients with renal dysfunction and CCE from April 2007 to May 2018. This study included the patients who were treated with neither maintenance dialysis nor steroid before CCE diagnosis, and followed-up for kidney function until November 2019. We assessed whether eosinophilia at the time of CCE diagnosis was related to renal death after treating with steroid therapy. RESULTS: Thirty patients with pathologically diagnosed CCE were enrolled and followed-up for 11.0 (5.2-43.4) months. There were significant differences in the white blood cell count (p = 0.01), hemoglobin (p = 0.009), serum creatinine levels (p = 0.008), phosphate (p = 0.049), and Eo (p = 0.008) between the renal survival and renal death groups. Using the receiver operating characteristic curve analysis with Youden index, Eo of 810/µL showed 100% sensitivity and 69.6% specificity for detecting renal death (area under the curve: 0.839). Comparing the outcomes in patients having Eo ≥ and < 810/µL using the log-rank test, there is a significantly higher renal death rate in CCE patients with Eo ≥ 810/µL (p = 0.0016). CONCLUSION: Higher eosinophilia was a prognostic risk factor for renal death in the patients with CCE.

Gastric remnant necrosis secondary to cholesterol crystal embolization after distal gastrectomy in a gastric cancer patient: a case report.

BACKGROUND: Distal gastrectomy with lymph node dissection, a standard operative technique for gastric cancer treatment, is safely performed because the stomach has a rich vascular supply. Gastric remnant necrosis caused by cholesterol crystal embolization following distal gastrectomy has not been described previously. We report a case of gastric remnant necrosis in a patient with cholesterol crystal embolization. CASE PRESENTATION: A 70-year-old man with a history of cholesterol crystal embolization presented to our surgery department with complaints of anorexia and dysphasia. He was diagnosed with gastric cancer invading the pyloric antrum and underwent distal gastrectomy with Billroth 2 reconstruction. On postoperative day 11, he developed abdominal pain without fever. Emergency laparotomy revealed that most parts of the remnant stomach were necrosed. Total gastrectomy with Roux-en-Y reconstruction and abscess drainage were performed. After surgery, anastomotic leakage occurred and was treated conservatively. However, the superior pancreaticoduodenal artery aneurysm suddenly ruptured and he expired. CONCLUSIONS: Gastric remnant necrosis after distal gastrectomy can be a gastrointestinal presentation of cholesterol crystal embolization. Perioperative/intraoperative risk assessments such as preventive total gastrectomy or intraoperative assessment with indocyanine green fluorescence angiography may be desirable to avoid this complication.

[Cholesterol crystal embolism mimicking a DRESS]. / Des embolies de cristaux de cholestérol mimant un DRESS.

INTRODUCTION: Clinical presentation of cholesterol crystal embolism (CCE) can be dermatologic when cholesterol crystals become lodged in small cutaneous arteries resulting in ischemia. We report a case of CCE with erythroderma misleading to a diagnostic of drug reaction with eosinophilia and systemic symptoms (DRESS). CASE REPORT: A 66 year-old woman presented with erythroderma few months after initiation of allopurinol. Acute renal failure was present with elevation in plasma creatinine concentration (523µmol/L) and hypereosinophilia (HE) (5666/mm3). Finally, the REGISCAR score helped to rule out DRESS diagnostic. Past blood-count tests were analyzed revealing chronic HE present before allopurinol initiation. Renal biopsy identified CCE. CONCLUSION: This case is the first to report a DRESS like presentation of CCE. Clinical findings are secondary to HE and not to occlusion of cutaneous arteries.