Tuesday Clinical Case Conference

1. Tuesday Clinical Case Conference 9/11/07 Zae Kim

2. Atheroembolic disease (Cholesterol Crystal Embolism) • Epidemiology • Clinical and pathologic findings • Diagnosis • Pathogenesis • Treatment

3. 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?

4. Epidemiologyretrospective autopsy studyantemortem biopsy study

5. Incidence:retrospective autopsy studies

6. Incidence:antemortem biopsy studies

7. Incidence:

8. Risk factors

9. Risk factors

10. Risk factors

11. Risk factors

12. Age >60 Male gender White HTN Tobacco use DM Atherosclerosis CAD AAA PVD Risk factors

13. Clinical and laboratory presentation

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

15. Clinical Presentation

17. Clinical and Laboratory Presentation

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

19. Clinical and Laboratory Presentation

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

21. outcome

22. outcome

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

24. 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

25. 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--f10.fig?tocnode=50835407

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

27. 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

28. 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

29. 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

30. 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

31. 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

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

33. Eosinophilia Eosinophiluria

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

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

36. 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

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

38. 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

39. 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)

40. The end