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Tuesday Clinical Case Conference . 9/11/07 Zae Kim. Atheroembolic disease (Cholesterol Crystal Embolism) . Epidemiology Clinical and pathologic findings Diagnosis Pathogenesis Treatment. Atheroembolic Renal Disease (AERD). An underdiagnosed and increasing cause of renal failure

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Atheroembolic disease cholesterol crystal embolism l.jpg
Atheroembolic disease (Cholesterol Crystal Embolism)

  • Epidemiology

  • Clinical and pathologic findings

  • Diagnosis

  • Pathogenesis

  • Treatment


Atheroembolic renal disease aerd l.jpg
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?


Epidemiology retrospective autopsy study antemortem biopsy study l.jpg
Epidemiologyretrospective autopsy studyantemortem biopsy study


Incidence retrospective autopsy studies l.jpg
Incidence:retrospective autopsy studies


Incidence antemortem biopsy studies l.jpg
Incidence:antemortem biopsy studies







Risk factors12 l.jpg

Age >60

Male gender

White

HTN

Tobacco use

DM

Atherosclerosis

CAD

AAA

PVD

Risk factors



Clinical features l.jpg
Clinical Features

  • Atheroembolic renal disease is part of a multisystem

  • Renal

    • ~50% patients affected

      • Multiple presentation

        • Acute

        • Subacute

        • Chronic




Slide18 l.jpg
GI

Gastric mucosal and submucosal biopsy

-cholesterol crystals in the submucosal arterioles



Cholesterol crystals lodged in the retinal vessels hollenhorst plaques on funduscopic examination l.jpg
Cholesterol crystals lodged in the retinal vessels (Hollenhorst plaques) on funduscopic examination.


Slide21 l.jpg

outcome (Hollenhorst plaques) on funduscopic examination.


Outcome l.jpg
outcome (Hollenhorst plaques) on funduscopic examination.



Laboratory features l.jpg
Laboratory Features disseminated CCE

  • 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


Pathogenesis l.jpg
Pathogenesis disseminated CCE

  • 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--f10.fig?tocnode=50835407


Atheroma l.jpg
Atheroma disseminated CCE

  • How vulnerable plaque is formed…

    • Fat droplet absorption

    • Cytokine release

    • Inflammation

    • Monocyte->macrophage

    • Further fat collection

  • The fat-filled cells form a plaque with a thin covering.

http://heart.health.ivillage.com/cholesterol/heartattack3.cfm


Pathology l.jpg
Pathology disseminated CCE

  • 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


Histologic features l.jpg
Histologic features disseminated CCE

  • 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


Diagnosis l.jpg
Diagnosis disseminated CCE

  • “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


Definitive diagnosis biopsy l.jpg
Definitive diagnosis - biopsy disseminated CCE

  • 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


Treatment l.jpg
Treatment disseminated CCE

  • 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



Eosinophilia l.jpg
Eosinophilia hypocomplementemia?

Eosinophiluria


Hypocomplementemia l.jpg
Hypocomplementemia hypocomplementemia?

  • Complement and inflammatory response may play a role in pathogenesis of AERD.

    • Hammerschmidt (J lab Clin med 1981)…


Slide35 l.jpg

Generation of PMN-aggregating activity in plasma incubated with lipids extracted from atheromatous aortas

Aggregating activity of PMN


Role of steroid l.jpg
Role of steroid? with lipids extracted from atheromatous aortas

  • Use of corticosteroid was associated with 100% mortality (Fine, Agiology, 1987)

  • Belenfant’s experience (1999)

    • N=18

    • 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


Conclusion l.jpg
conclusion with lipids extracted from atheromatous aortas

  • Under-recognized cause of kidney failure

    • Think about it before precipitating risk

    • Think about it in your differential

    • Look for it


Slide38 l.jpg
Belenfant: Supportive treatment improves survival in multivisceral cholesterol crystal embolism. Am J Kidney Dis 1999, 33:840-850.

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


Belenfant l.jpg
Belenfant multivisceral cholesterol crystal embolism. Am J Kidney Dis 1999, 33:840-850.

  • Larges series to date, n=67, w catastrophic atheroembolism

  • Prospective with f/u to 4 yrs

  • N=2102 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)


The end l.jpg
The end multivisceral cholesterol crystal embolism. Am J Kidney Dis 1999, 33:840-850.