Tuesday Clinical Case Conference

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Tuesday Clinical Case Conference
9/11/07 Zae Kim
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Atheroembolic disease (Cholesterol Crystal
Embolism)

• Epidemiology
• Clinical and pathologic findings
• Diagnosis
• Pathogenesis
• Treatment

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Atheroembolic Renal Disease (AERD)

• An underdiagnosed and increasing cause of renal
  failure
• Caused by showers of cholesterol crystals from an
  atherosclerotic aorta that occlude small renal
  arteries
• Often multisystemic
• Iatrogenic complication
• Treatment?

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Epidemiologyretrospective autopsy
studyantemortem biopsy study
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Incidenceretrospective autopsy studies
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Incidence antemortem biopsy studies
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Incidence
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Risk factors
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Risk factors
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Risk factors
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Risk factors
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Risk factors

• Age gt60
• Male gender
• White
• HTN
• Tobacco use
• DM
• Atherosclerosis
• CAD
• AAA
• PVD

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Clinical and laboratory presentation
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Clinical Features

• Atheroembolic renal disease is part of a
  multisystem
• Renal
• 50 patients affected
• Multiple presentation
• Acute
• Subacute
• Chronic

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Clinical Presentation
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(No Transcript)
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Clinical and Laboratory Presentation
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GI
Gastric mucosal and submucosal biopsy -cholesterol
crystals in the submucosal arterioles
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Clinical and Laboratory Presentation
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Cholesterol crystals lodged in the retinal
vessels (Hollenhorst plaques) on funduscopic
examination.
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outcome
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outcome
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Survival rate (Kaplan Meier) of 67 patients with
disseminated CCE
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Laboratory Features

• Variable and NONE ARE PATHOGNOMIC
• Serum chemistry
• Elevated BUN, creatinine
• amylase, CPK, LFTs
• Hematology
• leukocytosis, thrombocytopenia, and eosinophilia
• Elevated ESR, CRP
• Serologic
• Elevated ESR
• Decreased serum complement
• Urine (abnormal but nonspecific)
• proteinuria, hematuria, eosinophilia

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Pathogenesis

• Flory (1945)
• 267 consecutive autopsies
• 9 cases of cholesterol crystal embolism
• 2/147 (1) with moderate aortic plaque erosion
• 7/57 (12) with severe aortic plaque erosion
• 0 in 63 cases with absence of aortic plaque
  ulceration

http//www.mdconsult.com/das/book/body/77638334-4/
620123283/1201/I4-u1.0-B0-7216-0164-2..50036-7--f1
0.fig?tocnode50835407
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Atheroma

• How vulnerable plaque is formed
• Fat droplet absorption
• Cytokine release
• Inflammation
• Monocyte-gtmacrophage
• Further fat collection
• The fat-filled cells form a plaque with a thin
  covering.

http//heart.health.ivillage.com/cholesterol/heart
attack3.cfm
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Pathology

• CCE lodge in multiple small arteries (150-200 µm
  in diameter)
• Interlobular, afferent arterioles, terminal
  arterioles, and glomerular capillaries

Thin section, toluidine blue stain shows the
characteristic cholesterol clefts (due to washout
of the cholesterol crystals during histologic
processing) of an atheroembolus in the small
renal artery
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Histologic features

• In acute lesion
• Occlusion of lumen of small vessel
• Inflammatory response PMN leukocytes and
  eosinophils
• Later stage
• Foreign-body giant cells
• Endothelial proliferation
• Fibrous tissue surrounding the crystals

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Diagnosis

• great masquerader
• CCE is ubiquitous with random and variable
  distributions in the body
• Mimic many other clinical syndromes
• Ddx
• Vasculitis
• Subacute endocarditis
• Polymyositis
• Myoglobinuric renal failure
• Drug-induced interstitial nephritis
• Renal artery thrombosis or thromboembolism

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Definitive diagnosis - biopsy

• Biopsy
• Characteristic needle-shaped empty clefts within
  arterioles
• ghost cells because crystals are dissolved
  during tissue fixation
• Muscle, kidney, or skin
• Cutaneous biopsy with 92 yield

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Treatment

• No effective treatment available
• Secondary Prevention
• Avoid precipitating factors
• aggressive risk factor modification, and
• optimal medical mgmt of CVD
• smoking cessation, anti-platelet tx, and bp
  control, cholesterol and glucose
• Statin uncertain?
• Steroid?
• Surgical with clear embolic source

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What is the implication of eosinophilia/-uria and
hypocomplementemia?
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Eosinophilia
Eosinophiluria
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Hypocomplementemia

• Complement and inflammatory response may play a
  role in pathogenesis of AERD.
• Hammerschmidt (J lab Clin med 1981)

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Generation of PMN-aggregating activity in plasma
incubated with lipids extracted from atheromatous
aortas
Aggregating activity of PMN
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Role of steroid?

• Use of corticosteroid was associated with 100
  mortality (Fine, Agiology, 1987)
• Belenfants experience (1999)
• N18
• Patients with laboratory evidence of inflammation
• Corticosteroid treatment using prednisolone
  0.3mg/kg
• Outcome
• Therapy credited with the relief of lower limb
  and/or gastrointestinal pain and definite
  improvement in food intake and clinical status

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conclusion

• Under-recognized cause of kidney failure
• Think about it before precipitating risk
• Think about it in your differential
• Look for it

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Belenfant Supportive treatment improves survival
in multivisceral cholesterol crystal embolism. Am
J Kidney Dis 1999, 33840-850.

• Highlighted the potential benefits of avoiding
  further precipitating insults in conjunction with
  optmal medical management

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Belenfant

• Larges series to date, n67, w catastrophic
  atheroembolism
• Prospective with f/u to 4 yrs
• N2102 admit to renal intensive care unit over
  11-yr period
• Dx
• Based on clinical and histologic findings
• Excluded patients with other causes of acute or
  acute on chronic renal impairment (also excluded
  CIN or perioperative associated renal failure)

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The end