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.

Fatal Course of Cutaneous Cholesterol Embolization Syndrome: A Case Report.

Cholesterol embolization syndrome is an increasing but underestimated problem after endovascular intervention or after the start of thrombolytic therapies. Embolies from the aortic wall involves abdominal organs and the skin of the lower extremities or buttocks. In our case a progressive ulceration and necroses occurs spontaneously. Endovascular treatment of the lower extremities was successful for a short period. Due to the progression of necrosis, both legs were amputated. Biopsies were taken from the skin were initially no directions to the diagnosis of Cholesterol embolization syndrome. After a second elliptical excision biopsy the diagnosis of cholesterol embolization syndrome was confirmed. Because the rapid progression of skin necroses despite the treatment of prednisone, patient died due to sepsis and renal failure. This case shows when arterial revascularization is performed and progression in skin necrosis occurs despite optimal arterial vascular status the diagnosis CES should be considered and treated in an early state of disease.

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.

Efficacy of LDL apheresis for the treatment of cholesterol crystal embolism: A prospective, controlled study.

This study was performed to evaluate the efficacy and safety of LDL apheresis (LDL-A) for the treatment of cholesterol crystal embolism (CCE) after cardiovascular procedures. We conducted a prospective multicenter study of 34 patients with CCE and 15 historical control patients. The present participants underwent six sessions of LDL-A for 4 weeks and underwent medical therapy with corticosteroids and statins. The mean creatinine concentration and estimated glomerular filtration rate at baseline were 3.82 ± 2.29 mg/dL and 17.8 ± 9.9 mL/min/1.73 m2 , respectively. The prevalence of maintenance dialysis at 24 weeks was significantly lower in the present participants than in the historical controls (3.1% vs. 40.0%, respectively; p < 0.0001), but the mortality rate at 24 weeks was comparable (19% vs. 33%, respectively). Although 45 adverse events occurred in 23 participants, there were no unexpected adverse events. LDL-A for CCE reduces the prevalence of maintenance dialysis 24 weeks later and is well tolerated. This study was registered in the Japan Registry of Clinical Trials (jRCTs022180029) and clinicaltrials.gov (NCT01726868).

Use of Proprotein Converse Subtilisin/Kexin Type 9 Inhibitor to Treat Cholesterol Crystal Embolisms after Catheterization: A Report of Three Cases.

Cholesterol crystal embolism (CCE) is a serious complication that occurs after cardiac and vascular procedures. CCE involves multiple organs, and the prognosis and renal function of patients is poor. Although the efficacy of steroid, statin, and low-density lipoprotein apheresis has been reported, no definitive treatment has been established. We herein report three consecutive cases treated with conventional steroid therapy with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor after catheterization. The renal function was preserved, steroid therapy was stopped, and wound healing of blue toes was achieved. PCSK9 inhibitor therapy was safe in the present patient and may be a potential treatment option for 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.

¿Quién disparó primero? Infarto renal de tres posibles causas / Who shot first? Three possible causes of a kidney infarction

El infarto renal agudo (IRA) es una patología con frecuencia inferior al 1% y diagnóstico complejo. Puede manifestarse como dolor abdominal o en fosa renal, asociando náuseas, vómitos, fiebre o incluso hipertensión, entre otros. El diagnóstico está basado en una alta sospecha clínica, con elevación de lactato deshidrogenasa (LDH) en los análisis y angio-TC con defecto de perfusión renal parenquimatosa en cuña. En cuanto a la etiología del IRA, podemos distinguir dos grupos etiológicos: tromboembólicos y trombosis in situ. Es importante realizar un adecuado diagnóstico causal para realizar un tratamiento correcto.(AU)

Renal infarction is a rare disease whose incidence is less than 1%. The symptoms can be abdominal or flank pain, nausea, vomiting, fever or hypertension. The diagnosis is complex, and it is based on symptoms, blood analysis with an elevated level of lactate dehydrogenase and computed tomography angiography. The two major causes of renal infarction are thromboembolism and in situ thrombosis. The treatment depends on an adequate etiological diagnosis.(AU)