Cholesterol emboli-induced renal failure and gastric ulcer after thrombolytic therapy.Abstract: Cholesterol embolization syndrome cholesterol embolization syndrome Atheroembolic renal disease Vascular disease A condition affecting ± 4/10,000, more common in ♂ ≥ age 60, in which showers of cholesterol and debris from atherosclerotic plaques embolize to renal arterioles, is a rare but devastating complication of thrombolysis. Clinical presentations are variable, which has resulted in labeling this syndrome as the great masquerader. Almost every organ in the body may be affected, but the syndrome commonly involves the kidney, skin, central nervous system, and gastrointestinal tract. Treatment is mainly supportive, with an emphasis on reducing the risk of recurrence. The case presented is a unique one of thrombolytic-induced cholesterol embolization syndrome causing renal failure, in which the diagnosis was supported by a biopsy of a gastric ulcer.
Key Words: cholesterol emboli emboli /em·bo·li/ (em´bo-li) plural of embolus.
Plural of embolus. An embolus is something that blocks the blood flow in a blood vessel. , renal failure, thrombolysis
Thrombolytic-induced cholesterol embolization syndrome (CES) was first recognized in 1984 by Glassock et al (1) in a patient who had acute renal failure acute renal failure Acute kidney failure Nephrology An abrupt decline in renal function, triggered by various processes–eg, sepsis, shock, trauma, kidney stones, drug toxicity-aspirin, lithium, substances of abuse, toxins, iodinated radiocontrast. , hypertension, and skin necrosis after receiving streptokinase streptokinase /strep·to·ki·nase/ (-ki´nas) a protein produced by ß, which produces fibrinolysis by binding to plasminogen and causing its conversion to plasmin; used as a thrombolytic agent. for a deep vein thrombosis A blood clot (thrombos) in a vein deep within the muscle, typically in the thigh or calf. It is caused by disease or the lack of activity such as sitting for hours at a computer screen. . Multiple case reports followed as thrombolysis became more widespread for deep vein thrombosis, myocardial infarctions, (2-4) and pulmonary emboli.
CES is notoriously difficult to diagnose, (5) perhaps explaining why large trials of thrombolytic therapy have not included this syndrome as a complication. Clinicians should be aware of this syndrome, given its potentially devastating effect on the patient. The presentation of CES is variable. In this report, we describe a patient who received reteplase for an acute myocardial infarction acute myocardial infarction (·kyōōtˑ mī·ō·karˑ·dē· and subsequently had acute renal failure and a biopsy-proven bleeding gastric ulcer attributed to CES.
A 68-year-old, female ex-smoker who had not seen a physician for about 25 years presented with chest pain associated with nausea and diaphoresis diaphoresis /di·a·pho·re·sis/ (-fah-re´sis) sweating, especially of a profuse type.
Perspiration, especially when copious and medically induced. . An acute inferior myocardial infarction was diagnosed by electrocardiography electrocardiography (ĭlĕk'trōkärdēŏg`rəfē), science of recording and interpreting the electrical activity that precedes and is a measure of the action of heart muscles. . She was treated with reteplase followed by a heparin infusion. After administration of the thrombolytic agent, she had an episode of hypotension (70/38) that responded to fluids. At admission, her creatinine level was 2 mg/dL. She was unaware of any prior kidney disease. The only medication she was taking was aspirin for occasional arthralgias.
Her kidney function deteriorated throughout her hospital stay. On hospital day 8, her creatinine level was 3.2 mg/dL when she underwent a cardiac catheterization. In preparation for this procedure, she was treated with acetylcysteine and intravenous fluid hydration in an attempt to minimize dye-induced renal injury.
Additional laboratory evaluation revealed peripheral eosinophilia eosinophilia /eo·sin·o·phil·ia/ (e?o-sin?o-fil´e-ah) abnormally increased eosinophils in the blood.
An increase in the number of eosinophils in the blood. , which was evident the day after thrombolytic agents were given and persisted until initiation of hemodialysis. The eosinophil eosinophil /eo·sin·o·phil/ (e?o-sin´o-fil) a granular leukocyte having a nucleus with two lobes connected by a thread of chromatin, and cytoplasm containing coarse, round granules of uniform size. count ranged between 500 to 1,500 cell count/[mm.sup.3]. Her urine analysis did not show any proteinuria proteinuria /pro·tein·uria/ (-ur´e-ah) an excess of serum proteins in the urine, as in renal disease or after strenuous exercise.proteinu´ric
1. , hematuria hematuria
Blood in the urine. It usually indicates injury or disease of the kidney or another structure of the urinary system or possibly, in males, the reproductive system. It may result from infection, inflammation, tumours, kidney stones, or other disorders. , or eosinophiluria. A renal ultrasound showed an atrophic left kidney. C3, C4, antinuclear antibody, antineutrophil cytoplasmic antibody antineutrophil cytoplasmic antibody ANCA Immunology Any autoantibody directed against certain components of granulocytes, myeloid-specific lysosomal enzymes; ANCAs are most commonly found in systemic vasculitides–eg, necrotizing vasculitis, active generalized , hepatitis B virus, and hepatitis C virus were all negative.
In the first week of her hospital stay, the patient complained of epigastric epigastric adjective Referring to the body region between the costal margins and the subcostal plane discomfort. She had development of melena melena /me·le·na/ (me-le´nah) the passage of dark stools stained with altered blood.
n. the day after her cardiac catheterization. An esophagoduodenoscopy revealed erosive gastritis with multiple shallow gastric ulcers. A biopsy of the gastric mucosa revealed cholesterol crystal clefts in the lumen of the arterioles Arterioles
Small blood vessels that carry arterial (oxygenated) blood.
Mentioned in: Retinal Artery Occlusion
n (Figure). A proton pump inhibitor proton pump inhibitor
A class of drugs that inhibit gastric acid secretion by interfering with the movement of hydrogen ions across cell membranes and are used mainly to treat peptic ulcers, gastroesophageal reflux disease, and esophagitis. was started.
Her kidney function did not improve despite a 2-week course of prednisone. She refused a kidney biopsy and was eventually started on hemodialysis and remains dialysis dependent 10 months after her myocardial infarction. During this time, she was readmitted multiple times to the intensive care unit for volume overload.
Cholesterol embolization syndrome has been associated with angiographic procedures, aortic surgery, and anticoagulation therapy. Over the past two decades, an association with thrombolytic therapy has been noted, although rarely.
A prospective study to assess the incidence of CES after thrombolytic therapy was published in 1995 by Blankenship et al. (6) CES was found in 14% of the 21 patients treated with thrombolytic therapy and in 10% of the 31 patients without thrombolytic therapy (P = NS). Some of the limitations of this study noted by the authors included the small sample size and a more limited tissue sampling in live patients compared with that available at autopsy. Larger studies are needed to find or exclude a relation between thrombolytic therapy and CES.
The proposed mechanism for thrombolytic-induced CES is the disruption or dissolution of the protective thrombi thrombi /throm·bi/ (throm´bi) plural of thrombus. that cover ulcerated Ulcerated
Damaged so that the surface tissue is lost and/or necrotic (dead).
Mentioned in: Adenoid Hyperplasia plaques, thereby exposing the inner lipid pool to the systemic circulation. (7)
The onset of clinical symptoms is variable and dependent on the mechanism for cholesterol release. Thrombolytic therapy and invasive vascular procedures have a relatively rapid onset of hours to days to weeks. Signs and symptoms of CES induced by anticoagulants such as warfarin and heparin may occur weeks to months later. These agents do not directly disrupt fibrin clots but may slowly weaken them by inhibition of the normal remodeling that occurs within a clot or by spontaneous hemorrhage within the clot itself, (8) thereby causing its dislodgment.
The prognosis of CES is poor, and the treatment has been mainly supportive. Several measures should be taken to reduce the likelihood of recurrence. (9) This involves stopping all forms of anticoagulation regardless of the cardiac or vascular status of the patient; however, prosthetic heart valves have not been taken into account in the current literature. Invasive vascular procedures should be avoided. Many patients with renal involvement required hemodialysis, and few regained renal function. (9) Case reports have suggested a beneficial role for statins in stabilizing the cholesterol-rich atherosclerotic plaques, resulting in improved renal function and lower-limb ischemia. (10,11) Statins not only have a cholesterol-lowering effect but also anti-inflammatory and immunomodulatory properties, which may play a role in plaque stabilization. (12) In a prospective study of atheroembolic renal disease, patients who had end-stage renal disease End-stage renal disease (ESRD)
Total kidney failure; chronic kidney failure is diagnosed as ESRD when kidney function falls to 5-10% of capacity.
Mentioned in: Chronic Kidney Failure
end-stage renal disease were less likely to be under statin treatment. (13)
The role of corticosteroids in treating CES is controversial. The initial insult to the kidney from cholesterol emboli may be the ischemic Ischemic
An inadequate supply of blood to a part of the body, caused by partial or total blockage of an artery.
Mentioned in: Antiangiogenic Therapy, Subarachnoid Hemorrhage, Ventricular Fibrillation
ischemic process. However, the inflammatory reaction that follows aggravates and perpetuates the injury. High-dose steroids have resulted in dramatic improvement in some case reports. (14) A report also described a case in whom the tapering of steroids coincided with a recurrence of symptoms of cholesterol embolism. (15) In some cases, steroid therapy had limited or no effect. However, the steroid dose and duration of treatment may not have been sufficient. (16) Plasma exchange in conjunction with corticosteroid therapy has also been used for the treatment of CES. (16) However, both high-dose steroid therapy and plasma exchange have not been studied extensively in CES to reach a definite conclusion on their efficacy.
Thrombolytic-induced CES is a rare but devastating complication. Knowledge about the varying presentations of CES will allow early diagnosis and targeted therapy in an attempt to minimize recurrence. In terms of treatment, there are many questions that need to be answered. Further basic and clinical research is required to reduce the morbidity and mortality associated with CES.
Never mistake motion for action. --Ernest Hemingway
The authors extend special thanks to Dr. Michael Sutters for his review of the article and Dr. Joel Hammer for his aid with photos.
Accepted October 20, 2004.
1. Glassock RJ, Ritz E, Bommer J, et al. Acute renal failure, hypertension and skin necrosis in a patient with streptokinase therapy. Am J Nephrol 1984;4:193-200.
2. Schwartz MW, McDonald GB. Cholesterol embolization syndrome: occurrence after intravenous streptokinase therapy for myocardial infarction. JAMA JAMA
Journal of the American Medical Association 1987;258:1934-1935.
3. Ridker PM, Michel T. Streptokinase therapy and cholesterol embolization. Am J Med 1989;87:357-358.
4. Wong FK, Chan SK, Ing TS, Li CS. Acute renal failure after streptokinase therapy in a patient with acute myocardial infarction. Am J Kidney Dis 1995;26:508-510.
5. Darsee JR. Cholesterol embolism: the great masquerader. South Med J 1979;72:174-180.
6. Blankenship JC, Butler M, Garbes A. Prospective assessment of cholesterol embolization in patients with acute myocardial infarction treated with thrombolytic therapy vs conservative therapy. Chest 1995;107:662-668.
7. Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: a review of 221 cases in the English literature. Angiology angiology /an·gi·ol·o·gy/ (an?je-ol´ah-je) the study of the vessels of the body; also, the sum of knowledge relating to the blood and lymph vessels.
8. Pennington M, Yeager J, Skelton H, Smith KJ. Cholesterol embolization syndrome: cutaneous histopathologic features and the variable onset of symptoms in patients with different risk factors. Br J Dermatol 2002;146:511-517.
9. Belenfent X, Meyrier A, Jacquot C. Supportive treatment improves survival in multivisceral cholesterol crystal embolism. Am J Kidney Dis 1999;33:840-850.
10. Woolfson RG, Lachmann H. Improvement in renal cholesterol emboli syndrome after simvastatin. Lancet 1998;351:1331-1332.
11. Cabili S, Hochman I, Goor Y, Reversal of gangrenous lesions in the blue toe syndrome blue toe syndrome Cardiology Atherothrombotic microembolism of lower extremities due to recurrent cholesterol embolic 'showers' with painful cyanotic discoloration of toes and embolism elsewhere, resolving between attacks; despite the gangrenous appearance, BTs may with lovastatin: a case report. Angiology 1993;44:821-825.
12. Blanco-Colio LM, Tunon J, Martin-Ventura JL, Egido J. Antiinflammatory and immunomodulatory effects of statins. Kidney Int 2003;1:12-23.
13. Scolari F, Ravani P, Pola A, et al. Predictors of renal and patient outcomes in atheroembolic renal disease: a prospective study. J Am Soc Nephrol 2003;14:1584-1590.
14. Dahlberg PJ, Frecentese DF, Cogbill TH. Cholesterol embolism: experience with 22 histologically proven cases. Surgery 1989;105:737-746.
15. Rosanosky SJ. Multiple cholesterol emboli syndrome multiple cholesterol emboli syndrome A condition of subacute onset caused by showers of emboli occurring days to wks–or months–after coronary artery catheterization or aortic surgery, causing ischemia of affected organs . South Med J 1982;75:677-680.
16. Hasegawa M, Kawashima S, Shikano M, et al. The evaluation of corticosteroid therapy in conjunction with plasma exchange in the treatment of renal cholesterol embolic disease: a report of 5 cases. Am J Nephrol 2000;20:263-267.
RELATED ARTICLE: Key Points
* Thrombolytic-induced cholesterol embolization syndrome has been rarely reported.
* Cholesterol embolization syndrome may affect every organ.
* A definite diagnosis depends on documenting cholesterol clefts in affected organs.
* Treatment is mainly supportive.
Wassim A. Hitti, MD, and John Anderson, MD
From the Department of Internal Medicine. Franklin Square Hospital Center Franklin Square Hospital Center is a hospital located in the White Marsh area of eastern Baltimore County, Franklin Square is the third largest hospital in Maryland. Employing more than 2,800 employees, Franklin Square is one of the largest employers in Baltimore County. , Baltimore, MD.
No financial support was required for this case report.
The author does not have any commercial or proprietary interest in any drug, device, or equipment mentioned in the submitted article.
Reprint requests to Dr. Wassim A. Hitti, Department of Internal Medicine, Franklin Square Hospital Center, 1 East University Parkway #1111, Baltimore, MD 21218. Email: email@example.com