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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2021  |  Volume : 32  |  Issue : 5  |  Page : 1489-1494
A case of cholesterol embolization syndrome mimicking rapidly progressive renal failure causing end-stage kidney disease


1 Department of Cardiology, Command Hospital Air Force, Bengaluru, Karnataka, India
2 Department of Nephrology, Command Hospital Air Force, Bengaluru, Karnataka, India
3 Department of Rheumatology, Command Hospital Air Force, Bengaluru, Karnataka, India
4 Department of Medicine, Command Hospital Air Force, Bengaluru, Karnataka, India

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Date of Web Publication4-May-2022
 

   Abstract 


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.

How to cite this article:
Bhat KG, Jha VK, Kumar M H, Vikrant, Mahapatra D. A case of cholesterol embolization syndrome mimicking rapidly progressive renal failure causing end-stage kidney disease. Saudi J Kidney Dis Transpl 2021;32:1489-94

How to cite this URL:
Bhat KG, Jha VK, Kumar M H, Vikrant, Mahapatra D. A case of cholesterol embolization syndrome mimicking rapidly progressive renal failure causing end-stage kidney disease. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 May 25];32:1489-94. Available from: https://www.sjkdt.org/text.asp?2021/32/5/1489/344775



   Introduction Top


Cholesterol embolization syndrome (CES) is a life-threatening but under-diagnosed complication of endovascular intervention and anticoagulation in older patients with diffuse atherosclerosis and ulcerated aortic plaques.[1] Herein, we present a case of CES with cutaneous, digital, renal, and retinal involvement after performing percutaneous coronary intervention (PCI) in a patient with acute myocardial infarction (MI). His initial presentation resembled rapidly progressive glomerulonephritis with vasculitis syndrome. He gradually progressed to end-stage kidney disease (ESKD) within two months warranting maintenance hemodialysis (HD).


   Case Report Top


A 63-year-old male, nonsmoker, a diabetic, and hypertensive, on regular medication (tablet metformin 500 mg twice a day, tablet telmisartan 40 mg twice a day, tablet sitagliptin 50 mg twice daily) since 2010, reported to emergency with rest angina and breathlessness of 6 h duration. He was diagnosed as a case of ST-elevation anterior wall MI based on electrocardiogram features and Troponin T positivity. Screening echocardiography showed ejection fraction of 30% and regional wall motion abnormality in anterior wall. On examination his pulse - 88/min, blood pressure (BP) - 110/80 mm Hg right arm supine, respiratory rate – 20 breaths/min, oxygen saturation - 98% on room air and systemic examination was normal. He was immediately taken up for primary angioplasty in MI (PAMI). Coronary angiography revealed a critical lesion in the left anterior descending artery (90% obstruction with thrombus laden lesion in proximal to mid segment) for which angioplasty and stenting (drug-eluting stent 3 mm × 33 mm) was done with good results [Figure 1]. There was no evidence of blood loss or hypotension during angiography. He underwent optical coherence tomography-guided optimization of stent one week later as per routine institutional practice [Figure 2].
Figure 1: (a) Coronary angiogram showing 90% occlusion with thrombus in mid-segment of the left anterior descending artery (arrow). (b) Post angioplasty and stenting angiogram showing good flow (arrow).

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Figure 2: Optical coherence tomography guided optimization of the stent (Unexpanded and malapposed segments were dilated with non-compliant balloons and achieved good result).

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His renal function test was normal (serum creatinine - 1.1 mg/dL). There was no evidence of diabetic retinopathy/diabetic nephropathy. He was discharged after three days in a stable condition with serum creatinine (Cr) - 1.0 mg/dL. The patient reported back after two weeks with complaints of bluish discoloration and pain in both feet for the past 10 days [Figure 3]. Clinical examination revealed - elevated BP (202/112 mm Hg right arm supine), palpable and bilaterally symmetrical all peripheral pulses, and normal antebrachial index. Peripheral cyanosis and livedo reticularis were noticed in both feet. There was no history of hemoptysis, hematuria, oliguria, or any uremic symptoms. His antiplatelet drugs, antihypertensives, and statins were continued. Oral clonidine and amlodipine were added to optimize BP. He was managed with injection methylprednisolone and other supportive measures for possible vasculitis. Laboratory investigations revealed raised erythrocyte sedimentation rate - 84 mm fall in 1 h, anemia (Hb - 10.6 g/dL), and deranged renal function (blood urea nitrogen/Cr - 41/4.98 mg/dL). Urine routine/microscopic examination revealed protein ++, 8–10 RBC/ high power field, no eosinophils. Lipid profile was normal. Ultrasound abdomen including kidney size and renal Doppler was normal. His autoimmune marker workup (antinuclear antibody, rheumatoid factor, anti-citrullinated protein antibody, antineutrophil cytoplasmic antibody, antiphospholipid antibody, C3/C4 Complement level) was normal. Anti-glomerular basement membrane antibody (anti-GBM) was <7 IU/mL (within reference range). Repeat two-dimensional Echo showed ejection fraction of 40% and no evidence of infective endocarditis. Subsequently, he developed worsening severe pain in both toes and gangrene of toes requiring surgical amputation (2nd, 3rd, 4th right toe, and 2nd left toe). With worsening symptoms and a history of angioplasty in the recent past, differential diagnosis of CES was considered after ruling out systemic vasculitis. Fundoscopy was done which revealed Hollenhorst plaque [Figure 4]. There was no evidence of hypertensive retinopathy. In view of gradual worsening of renal function and subnephrotic range proteinuria (24 h urinary protein - 1.8 g) with microscopic hematuria, a renal biopsy was done. Renal biopsy on light microscopy revealed features of chronic tubulointerstitial changes with interstitial fibrosis and tubular atrophy - 25%, glomerulosclerosis - 15%. There was no evidence of diabetic nephropathy or thrombotic micro-angiopathy. Electron microscopy revealed needle-shaped atheroemboli in interlobularsized artery [Figure 5]. These characteristic histopathological features confirmed the diagnosis of CES. The individual remained on fortnightly follow up in renal clinic. He had progressive worsening of renal function despite adequate BP control. He remained on conservative management and gradually progressed to ESKD within two months. He is undergoing regular maintenance HD at present.
Figure 3: Picture depicting bluish discoloration of both feet (left side) followed by dry gangrene toes after a few days.

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Figure 4: Fundoscopy depicting bright yellow retinal plaque -Hollenhorst plaque (arrow).

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Figure 5: Renal biopsy image showing cholesterol (crystals) clefts in an arterial lumen (arrow) seen as empty, biconvex, and needleshaped clefts, appearing as “ghosts” – toluidine blue-stained semi-thin section from tissue processed for electron microscopy. The interlobular artery is obstructed by endarteritis and fibrosis (×400).

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The authors obtained all appropriate consent forms from the patient for the publication of this case report.


   Discussion Top


The spectrum of CES ranges from the discovery of a few crystals at autopsy to the life-threatening occurrence of multiorgan involvement.[2] In contrast to arterio-arterial thromboembolism which is characterized by an abrupt release of a few large emboli, CES is characterized by showers of microemboli.[3] In a prospective study of 1579 patients undergoing coronary angioplasty, clinical evidence of cholesterol embolization was found in only one patient (0.06% of cases).[4] The index case is one of the rare presentations of systemic atheroembolism involving multiple systems after PAMI. High clinical suspicion is critical for the diagnosis of this rare clinical entity.

In the setting of acute kidney injury that occurs after angiography, the primary differential diagnosis is contrast nephropathy and CES. Contrast nephropathy typically begins to recover within three to five days, while CES shows at best an incomplete recovery and a stuttering course with further showers of cholesterol crystals. Atheroemboli also tends to produce incomplete occlusion with secondary ischemic atrophy and as time progresses, a foreign body reaction often ensues, causing intimal proliferation, giant cell formation, and further narrowing of the vascular lumen.[5] Our patient presented with multisystem involvement including subacute kidney injury after one to two weeks of coronary angioplasty and progressed to irreversible renal dysfunction. Therefore, renal dysfunction after cholesterol embolization to the kidney may range anywhere on the spectrum from spontaneous resolution to ESKD requiring dialysis.

Skin findings are the most common clinical signs of CES, occurring in 34% of patients in one systematic review.[6] Although CES is often referred to as the “blue toe syndrome,” blue skin discoloration is less common than other skin findings and is present in 10–15%.[7] Our patient presented with bluish skin discoloration of feet, livedo reticularis, and gangrenous toes requiring surgical amputation. Hollenhorst plaques, considered as the telltale sign of the disease are bright, refractile lesions in the retina indicative of cholesterol crystal embolization from a proximal atherosclerotic source.[8] It should not be used to confirm the diagnosis. However, if clinical suspicion is very high, a tissue biopsy may be deferred in patients with CES if these retinal lesions are present.[8],[9]

In a prospective study by Fukumoto et al,[10] a total of 1786 consecutive patients 40 years of age and older were evaluated, who underwent left heart catheterization. The diagnosis was made when patients had renal dysfunction or peripheral cutaneous involvement. Twenty-five patients (1.4%) were diagnosed as having CES out of which 16 patients (64%) had renal dysfunction and twelve patients (48%) had cutaneous signs.[10] In another study by Fine et al,[6] out of 221 histologically proven cases of CES, renal involvement was present in 22.7%. The prognosis of renal dysfunction is influenced by disease type and severity.

Some cases of CES may be accompanied by nephrotic range proteinuria. In one study, 10 cases of focal segmental glomerulosclerosis were detected in 24 patients with CES.[11] Underlying diabetic nephropathy and malignant hypertension may also induce significant proteinuria.[11],[12] This case is unique in the sense that the individual presented with skin manifestations, gangrenous toes, and progressive renal dysfunction within two weeks of primary angioplasty. In view of features suggestive of rapidly progressive kidney failure/acute nephritic syndrome/systemic vasculitis, he underwent renal biopsy. The diagnosis was confirmed by renal biopsy, though it did not reveal any significant chronicity of the lesions/any features of crescentic glomerulonephritis. Despite best conservative management, relentless progression of the disease required surgical amputation of toes for gangrene and initiation of maintenance HD for severe uremia. It is therefore important to prognosticate the disease consequence to the concerned patient at the onset of symptoms.


   Conclusion Top


A clinical diagnosis of CES should be made when a potential inciting event like PCI is followed by delayed onset of renal dysfunction and signs of extrarenal atheroemboli. The clinical features may mimic rapidly progressive kidney failure/? systemic vasculitis. The definitive diagnosis may be made by renal or skin biopsy. In the absence of definitive therapy available at present, progressive worsening is noticed despite early diagnosis and appropriate conservative management.

Conflict of interest: None declared.



 
   References Top

1.
Meyrier A. Cholesterol crystal embolism: Diagnosis and treatment. Kidney Int 2006; 69:1308-12.  Back to cited text no. 1
    
2.
Li X, Bayliss G, Zhuang S. Cholesterol crystal embolism and chronic kidney disease. Int J Mol Sci 2017;18:1120-32.  Back to cited text no. 2
    
3.
Kronzon I, Saric M. Cholesterol embolisation syndrome. Circulation 2010;122:631-41.  Back to cited text no. 3
    
4.
Johnson LW, Esente P, Giambartolomei A, et al. Peripheral vascular complications of coronary angioplasty by the femoral and brachial techniques. Cathet Cardiovasc Diagn 1994;31: 165-72.  Back to cited text no. 4
    
5.
Thadhani RI, Camargo CA Jr., Xavier RJ, Fang LS, Bazari H. Atheroembolic renal failure after invasive procedures. Natural history based on 52 histologically proven cases. Medicine (Baltimore) 1995;74:350-8.  Back to cited text no. 5
    
6.
Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: A review of 221 cases in the English literature. Angiology 1987;38:769-84.  Back to cited text no. 6
    
7.
Falanga V, Fine MJ, Kapoor WN. The cutaneous manifestations of cholesterol crystal embolization. Arch Dermatol 1986;122:1194-8.  Back to cited text no. 7
    
8.
Babikian V, Wijman CA, Koleini B, Malik SN, Goyal N, Matjucha IC. Retinal ischemia and embolism. Etiologies and outcomes based on a prospective study. Cerebrovasc Dis 2001;12:108-13.  Back to cited text no. 8
    
9.
Wijman CA, Babikian VL, Matjucha IC, et al. Cerebral microembolism in patients with retinal ischemia. Stroke 1998;29:1139-43.  Back to cited text no. 9
    
10.
Fukumoto Y, Tsutsui H, Tsuchihashi M, Masumoto A, Takeshita A; Cholesterol Embolism Study (CHEST) Investigators. The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: A prospective study. J Am Coll Cardiol 2003;42:211-6.  Back to cited text no. 10
    
11.
Greenberg A, Bastacky SI, Iqbal A, Borochovitz D, Johnson JP. Focal segmental glomerulosclerosis associated with nephrotic syndrome in cholesterol atheroembolism: Clinicopathological correlations. Am J Kidney Dis 1997;29: 334-44.  Back to cited text no. 11
    
12.
Conlon PJ, O’Riordan E, Kalra PA. New insights into the epidemiologic and clinical manifestations of atherosclerotic renovascular disease. Am J Kidney Dis 2000;35:573-87.  Back to cited text no. 12
    

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Correspondence Address:
Vijoy Kumar Jha
Department of Nephrology, Command Hospital Air Force, Bengaluru - 560 007, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.344775

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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    Abstract
   Introduction
   Case Report
   Discussion
   Conclusion
    References
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