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 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

Incidence: retrospective autopsy studies

Incidence: antemortem biopsy studies

Incidence:

Risk factors

Age >60 Male gender White HTN Tobacco use DM Atherosclerosis –CAD –AAA –PVD

Clinical and laboratory presentation

Clinical Features Atheroembolic renal disease is part of a multisystem Renal –~50% patients affected Multiple presentation –Acute –Subacute –Chronic

Clinical Presentation

Clinical and Laboratory Presentation

GI Gastric mucosal and submucosal biopsy -cholesterol crystals in the submucosal arterioles

Clinical and Laboratory Presentation

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

outcome

Survival rate (Kaplan Meier) of 67 patients with disseminated CCE

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

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 4/ /1201/I4-u1.0-B f10.fig?tocnode=

Atheroma 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. heart.health.ivillage.com/cholesterol/hearta ttack3.cfm

Pathology CCE lodge in multiple small arteries ( 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 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 “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 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 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

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

Eosinophilia Eosinophiluria

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

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

Role of steroid? 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 Under-recognized cause of kidney failure –Think about it before precipitating risk –Think about it in your differential –Look for it

Belenfant: Supportive treatment improves survival in multivisceral cholesterol crystal embolism. Am J Kidney Dis 1999, 33: Highlighted the potential benefits of avoiding further precipitating insults in conjunction with optmal medical management

Belenfant 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