1. Nephrology Core Curriculum Atheroembolic Disease

2. Atheroembolic Disease Results from cholesterol crystals and other debris separating from atheromatous plaques, flow downstream, and lodge in small renal arteries, producing luminal occlusion, ischemia, and renal dysfunction

3. Atheroembolic Disease Unlike clot embolic disease which tends to produce complete arterial occlusion and renal infarction (with associated flank pain, hematuria, and elevated LDH with nl transaminases), atheroemboli are non-distensible and irregularly shaped. They therefore DO NOT CAUSE COMPLETE VESSEL OCCLUSION. There pathology is the result of a resulting foreign body reaction with 2nd vessel narrowing and ischemic nephropathy

4. Atheroembolic Disease

5. Atheroembolic Disease Pathology –lesion of small to medium-sized arteries arterioles and capillaries are less commonly affected –lesions can occur in any organ –cholesterol crystals rarely seen 2nd dissolution in tissue fixatives

6. Atheroembolic Disease Pathology –Histology depends on timing acutely- cholesterol crystals and thrombus sub-acute- macrophages which engulf cholesterol and endothelial proliferation –if crystals pierce the vessel wall-- intense perivascular inflammation with giant cells chronic- concentric fibrosis

7. Atheroembolic Disease Pathology –Glomerular pathology crystals may reach the glomeruli can take >9 months for dissolution (in experimental models) glomerular ischemia, glomerular collapse, and basement membrane wrinkling –2nd FSGS on occasion-- with rare nephrotic range proteinuria

8. Atheroembolic Disease Risk Factors Surgery on the aorta proximal to the renal arteries –AAA repair –CABG –Cardiac valve surgery –Other Angiography or angioplasty (2%) –esp renal artery angiography Intra-aortic balloon pump Anticoagulation or thrombolytic therapy Severe ulcerating atherosclerosis

9. Atheroembolic Disease Risk Factors Anticoagulation –thrombus overlying atheromatous plaques may bind and immobilize friable debris –anticoagulation or thrombolysis removes this protective covering and results in distal embolization

10. Atheroembolic Disease Associated findings/Clinical features Finding Hypertension Coronary Artery Disease CVA Congestive Heart Failure Diabetes % of cases 61 44 25 21 11

11. Atheroembolic Disease Associated findings/Clinical features As would be expected for a disease that complicates severe atherosclerosis, risk factors for atherosclerosis as well as evidence of disseminated atherosclerotic disease are commonly present 75% are male mean age of diagnosis is the mid-seventh decade

12. Atheroembolic Disease Associated findings/Clinical features Notable for its highly variable severity –manifestations depend on both the extent of renal involvement and the extrarenal sites affected Massive widespread embolization presents catastrophically with fever, stroke, abdominal pain, gastrointestinal bleeding due to bowel infarction and secondary sepsis

13. Atheroembolic Disease Frequency of organ involvement (at autopsy) Kidney75% Spleen52% Pancreas52% Gastrointestinal tract31% Adrenal glands20% Liver17% Brain14% Skin6%

14. Atheroembolic Disease Renal pathology SLOWLY deteriorating renal function –related to crystal shape vs. lumen of vessel –Scr increases 0.1 to 0.2 mg/dl with progression to ESRD over 30-60 days or longer –rarely have heavy proteinuria (associated with a secondary FSGS)

15. Atheroembolic Disease Cutaneous pathology Livedo reticularis of the lower extremities “blue toes” with preserved distal pulses digital ulceration with associated severe pain

16. Atheroembolic Disease Gastrointestinal –abdominal pain, anorexia, weight loss, and bleeding Central nervous system –stroke, diffuse cortical dysfunction, scotomata, field cuts, or blindness –classic, but rare, Hollenhorst plaque

17. Atheroembolic Disease Diagnosis Requires a high index of suspicion in patients at risk Lab abnormalities –acute phase leukocytosis increased ESR eosinophilia hypocomplementemia hyperamylasemia-- if pancreatic involvement urine sediment- non-specific

18. Atheroembolic Disease Diagnosis Differential Diagnosis –radiocontrast-induced ARF-- more rapid course, failure occurs immediately, with renal function reaching a nadir in 3-4 days, with recovery over a similar period –ischemic ATN- acute onset with expected urine sediment findings –systemic vasculitis-- similar skin, GI, and CNS manifestations, but usually with urine sediment abnl and other associated findings –allergic interstitial nephritis, cryoglobulinemia, myeloma, renal artery stenosis, hypertensive nephrosclerosis

19. Atheroembolic Disease Therapy and Outcome Supportive measures –local care of digital ischemia –analgesia for pain –digital amputation if tissue is not viable –stop anticoagulation –avoid repeat angiographic procedures –hemodialysis/PD as indicated-- occasionally patients recover sufficient function to discontinue