Case Discussion < Brief History >      A 64-year-old man, a chronic smoker, was admitted because of a worsening renal function. He had had type 2 diabetes mellitus for 15 years. Usually, his blood glucose levels before and after meals were around 130 and 200 mg/dl, respectively. The hemoglobin A1c (HbA1c) was around 8%. He also had had hypertension for 10 years which had been well-controlled with an angiotensin II receptor blocker. Since 6 months earlier before this admission, he started to develop exertional dyspnea, chest tightness or pain which might radiate to the jaw or left shoulder. These symptoms could be relieved by immediate resting. He visited another hospital where nitroglycerin was prescribed. Three weeks prior to admission, he experienced a sudden onset of chest pain with cold sweating which could not be relieved by nitroglycerin. Acute coronary syndrome was diagnosed at the emergency room, and percutaneous balloon angioplasty with stenting was performed immediately. During hospitalization, right flank pain developed and one episode of microscopic hematuria was detected by urine analysis. Two weeks after catheterization, he was discharged. However, three more weeks after discharge, worsening of renal function was detected. On admission, physical examination showed a man of 167 cm in height and 60 kg in weight. His temperature was 37.2 oC, blood pressure 132/86 mmHg, and pulse rate 82 beats per minute. A systolic murmur was heard over the cardiac apex, but there were no obvious abdominal bruits in the periumbilical and back area. The pulses in the four limbs were palpable, and there was no blood pressure discrepancy between them. The other examinations were unremarkable. Chest radiography showed normal heart size and clear lung fields. Serologies for autoimmune profiles were all negative. Other results of laboratory and radiologic investigations are shown in tables 1-4. Table 1. Results of CBC/DC & coagulation profiles: Day after 1st admission WBC K/μL RBC M/μL Hgb g/dL Hct % MCV fL Plt K/μL 0 12.51 4.55 10.6 31.8 92.3 470 5 10.12 4.35 10.2 30.8 92.6 440 14 9.85 4.45 10.5 31.7 92.4 460 Day after 2nd admission WBC K/μL RBC M/μL Hgb g/dL Hct % MCV fL Plt K/μL 0 9.73 4.71 11.0 33.5 92.2 450 3 9.85 4.70 10.9 33.4 92.3 451 5 9.80 4.72 11.1 33.3 92.3 450  Table 2. Results of blood biochemistry       Day after 1st admission BUN mg/dl Cre mg/dl Na mmol/l K mmol/l GOT U/l T-Bil mg/dl Alb g/dL 0 28 1.4 141 3.8 34 1.0 4.3 3 36 1.5 138 4.1 53 0.8   7 36 1.4     56     14 35 1.5     66 1.0   Day after 2nd admission BUN mg/dl Cre mg/dl Na mmol/l K mmol/l GOT U/l T-Bil mg/dl Alb g/dL 0 65 2.6 138 4.5 40 0.9 4.2 3 71 2.9 136 4.4 42     5 65 3.0 136 4.4 41     7 60 2.9 137 4.3 43     Table 3. Results of urine nalysis Day after 1st admission Appearance Sp. gr pH Protein mg/dL Glu g/dL Ketones O.B Urobil EU/dL Bil 0 Y;C 1.02 7.0 >300 － － － 0.1 － 5 Y;TT 1.02 7.0 >300 － － ＋ 0.1 － 14 Y;TT 1.01 7.0 >300 － － ＋ 0.1 － Day after 2nd admission Appearance Sp. gr pH Protein mg/dL Glu g/dL Ketones O.B Urobil EU/dL Bil 0 Y;C 1.05 7.0 >300 － － － 0.1 － 1 Y;C 1.04 7.0 >300 － － － 0.1 － 3 Y;C 1.03 7.0 >300 － － － 0.1 － Day after 1st admission Nitrite WBC RBC /HPF WBC /HPF EpithCell /HPF Cast /LPF Crystal Bact 0 － － 0-1 0-1 0-3 － － － 5 － ＋ 20-30 10-20 3-5 － － － 14 － ＋ 10-20 5-10 1-3 － － － Day after 2nd admission Nitrite WBC RBC /HPF WBC /HPF EpithCell /HPF Cast /LPF Crystal Bact 0 － － 5-10 0-1 0-3 － － － 1 － － 5-10 0-1 0-3 － － － 3 － － 0-1 0-1 0-3 － － －   24 hour urine total protein: 1.5 g/d Table 4. Results of renal sonography Size Right kidney, 10.8 cm; left kidney, 11.0 cm Shape Bilaterally normal Cortical thinkness Right kidney, 10 mm; left kidney, 11 mm (within normal limits) Central sinus No hydronephrosis Solid or cystic lesion Nil < Course and Treatment >      On admission, angiotensin II receptor blocker was discontinued because of acute renal failure. Renal biopsy was performed 3 days after admission, which revealed a cleft at the glomerular hilum, capillary wall thickening and wrinkling due to ischemia. Acute tubular necrosis and concentric fibrosis were also seen. Because of the clinical presentations and renal biopsy, cholesterol embolism- related acute renal failure was diagnosed which might have resulted from previous cardiac catheterization. Because of the stable general function, this patient was discharged at 10th day after admission. During follow-up at the outpatient clinic, his renal function improved gradually two months later. However, serum creatinine levels remained elevated compared with those at first discharge from this hospital. < Analysis >      Cholesterol atheroembolic kidney disease results when cholesterol crystals and other debris separate from atheromatous plaques, flow downstream, and lodge in small renal arteries, producing luminal occlusion, ischemia, and kidney dysfunction. Depending on the source and distribution of emboli, kidney disease might be the sole or predominant manifestation or simply one feature of a systemic illness characterized by multi-organ ischemia or infarction. Atheroembolism is now recognized as a cause of occult or reversible declines in kidney function. Recovery of function may follow extended survival on renal replacement therapy. Embolization might be spontaneous, particularly with severe aortic disease, but mechanical disruption of plaque during angiographic or surgical procedures usually precedes it. Irrespective of the area primarily targeted for imaging, passage of a catheter alone the ascending or descending aorta proximal to the renal arteries confers a risk of embolization to the kidneys. Our patient ever underwent cardiac catheterization five weeks before detection of abnormal renal function which is a major risk for cholesterol embolization. However, what needs to differentiate is contrast nephropathy and cholesterol embolization related kidney disease. Contrast nephropathy usually occurs immediately 24 to 48 hours after contrast media exposure; however, cholesterol embolization related kidney disease usually shows a protracted clinical course which might take weeks to months. Other risk factors include smoking history, male and old age. The mean age at diagnosis is in the mid-seventh decade. Furthermore, high C-reactive protein, HTN, multi-vessel coronary disease, and acute coronary syndrome are also suggestive.      The typical clinical presentations are either constitutional symptoms, such as fever, abdominal or flank pain, tachycardia or specific organ ischemia or infarction. Many organs or systems could be involved, such as brain, lung, kidney, intestine, muscular system, and endocrine system. Laboratory findings are usually non-specific. However, microscopic hematuria in renal involvement might be seen. In renal biopsy, the pathologic presentations are similar to what we saw in this case. The size of affected artery is typically around 200 μm. The typical lesion is cholesterol cleft, a space which is occupied by cholesterol crystal but lost during specimen preparation. Besides, ischemic changes of glomeruli with glomerular collapse and basement wrinkling will be seen.      Because cholesterol embolization is so rare, there's no available data from controlled trials for prevention or treatment. Whereas vasodilator prostaglandin infusions have also been used to increase blood flow and use of statins has been reported to improve survival, monitoring basic electrolytes and urine output is essential. Although most patients will show a gradual improvement later, patients with pre-existing renal impairment will be at higher risk of renal replacement therapy or mortality. < Reference > Harrison's principles of internal medicine 15th edition Comprehensive Clinical Nephrology 2nd edition Primer on Kidney Disease 4th edition. eMedicine, Cholesterol embolism. Last Updated: August 5, 2005 繼續教育考題 1. (C)  Cholesterol embolization的典型病理表現，何者正確？ A  Cholesterol particles in the glomerulus B  Fatty change of the glomerular cells C  Cholesterol cleft D  Macrophage with lipid inclusion 2. (D)  Cholesterol atheroembolic kidney disease的病因為何？ A  Spontaneous rupture of lipid plaque B  Catheterization-related C  Surgery-related D  All of above 3. (C)  Cholesterol atheroembolic kidney disease和Contrast media nephropathy的比較何者錯誤？ A  Both have variable renal failure severity B  Both related to some invasive procedures C  Similar time course D  All of obove 4. (B)  對Cholesterol atheroembolic kidney disease的臨床表現何者錯誤？ A  Usually constitutional symptoms, such as fever and abdominal pain B  Usually occurs immediately 24 to 48 hours after some procedures C  Possible combined with multi-organ ischemia symptoms D  All of above 5. (D)  對Cholesterol atheroembolic kidney disease治療的描述何者正確？ A  Mainly supportive care B  Low dose of aspirin C  Statins might be beneficial D  All of above 6. (A)  何者可提供Cholesterol atheroembolic kidney disease的確定診斷？ A  By biopsy B  Angiography C  Dual helical computer tomography D  None of above 答案解說 (C) The typical lesion is cholesterol cleft, a space which was occupied by cholesterol crystal but lost during specimen preparation. Besides, ischemic changes of glomeruli with glomerular collapse and basement wrinkling were also noted. (D) Embolization might be spontaneous, particularly with severe aortic disease, but mechanical disruption of plaque during angiographic or surgical procedures usually precedes it. (C) Cholesterol atheroembolic kidney disease and contrast media nephropathy usually result from invasive procedures like angiography, computer tomography imaging etc. Both diseases present variable renal failure severities from mild impairment to uremia which requires dialysis. Contrast nephropathy usually occurs immediately 24 to 48 hours after contrast media exposure; however, cholesterol embolization related kidney disease usually shows a protracted clinical course which might take weeks to months. (B) The typical clinical presentations are either constitutional symptoms like fever, abdominal or flank pain, tachycardia or specific organ ischemia or infarction. Cholesterol embolization related kidney disease usually shows a protracted clinical course which might take weeks to months. (D) Because cholesterol embolization is so rare, so there’s no available data from controlled trials for prevention or specific therapy. Whereas vasodilator prostaglandin infusions have also been use to increase blood flow and statin use was ever reported to improve survival. Basic electrolytes and urine output monitor are essential. But if patients have pre-existing renal impairment, there will be higher chance of dialysis or mortality. Most patients will show a gradual improvement later. (A) Demonstration of cholesterol crystals in occluded arterioles is the only definitive test for cholesterol embolism. Others examinations cannot confirm definitely.