By Donna J. Lager, M.D.
Atheroembolic renal disease is part of a multisystem disease caused by occlusion of small arteries and arterioles by cholesterol crystals arising from ulcerated atherosclerotic plaques (1). Because the aorta is the most common source of the emboli, areas most affected are the kidneys, intestine and lower extremities (1). The release of the cholesterol atheroemboli may be spontaneous, however is more often triggered by vascular trauma due to vascular catheters or surgery, and the use of anticoagulants and thrombolytic agents. Cholesterol atheroembolic disease is most commonly reported in Caucasian males over 60 years of age who have clinical evidence of atherosclerosis. Other risk factors include smoking, hypertension and diabetes mellitus (1-5).
Clinical and Laboratory Features
The clinical presentation of atheroembolic disease depends on the source and size of the cholesterol emboli and the number of organs affected. Symptoms may be mild and subtle and may go completely unrecognized, or may be catastrophic. Atheroembolic disease should be suspected in any elderly patient who presents with an unexplained myocardial infarction, stroke, mesenteric ischemia, acute renal failure, an ischemic extremity or cutaneous evidence of embolization (2). Commonly reported clinical signs include fever, myalgias, hypertension, livido reticularis and cyanotic changes in the skin, and distal gangrene or necrotic ulcers. Symptoms referred to the gastrointestinal tract, the central nervous system and retinal emboli have also been reported (4). Laboratory abnormalities reported include mild, transient eosinophilia and eosinophiluria, elevated erythrocyte sedimentation rate (ESR), increased amylase, abnormal liver function tests and elevated creatine kinase (CK). Hypocomplementemia and nephrotic range proteinuria have also been described (3, 4).
Atheroembolic renal disease (AERD) is a common manifestation and results from atheroemboli that originate in the suprarenal aorta and lodge in renal arcuate and interlobular arteries, arterioles and glomerular capillaries. Evidence of renal dysfunction is usually subacute with hypertension and progressive renal failure, however may rarely be more acute with flank pain and hematuria secondary to renal infarction (2). Approximately 80% of patients have serum creatinine levels of 2 mg/dl or greater at the time of presentation, and nearly 40% have advanced renal failure requiring dialysis (3). Atheroembolic renal disease has also been reported in renal allografts (2, 3, 5) with an incidence of approximately 0.4% (5). The source of the emboli may be the donor renal artery or from the aorta of an elderly recipient. The clinical course is variable and the atheroemboli may be an unexpected finding in a biopsy done for allograft dysfunction.
Because atheroemboli may be present focally within the kidney, careful evaluation of multiple levels is important. Vessels of any size may be involved from arcuate arteries to glomerular capillaries, which characteristically contain elongated, biconvex, transparent clefts surrounded by a variable inflammatory response (Figure 1).
The cholesterol in the atheroemboli is removed during tissue processing leaving behind clear cholesterol clefts. With progression of the disease there is eventual complete occlusion of the vessel lumen. Secondary acute ischemic changes may accompany the occlusion with subsequent progressive glomerulosclerosis and interstitial fibrosis.
Conditions that may mimic AERD clinically include systemic diseases such as bacterial endocarditis, systemic vasculitis and thrombotic thrombocytopenic purpura, as well as contrast nephropathy and ischemic acute renal failure. Renal failure associated with contrast nephropathy occurs within 48-72 hours after the dye infusion and generally resolves within 4 to 7 days (3) in contrast to AERD which has a more insidious onset. Ischemic acute renal failure has an immediate onset, is accompanied by hypotension and lacks systemic manifestations (2, 3).
Management and Prognosis
There is no specific therapy for AERD; however both surgical and medical interventions have shown some success. These include prosthetic bypass grafting, angioplasty and arterial reconstruction (2-4). Medical management has included the use of lipid lowering agents, low-dose corticosteroids, angiotensin blockade and low-density lipoprotein apheresis (2-4). Preventive measures include avoidance of anticoagulant therapy, invasive vascular procedures and vascular surgery in patients with extensive atherosclerotic disease as well as smoking cessation and control of hypertension.
Early studies prior to 1990 reported a dismal outcome with mortality rates ranging from 64% to 87%, however with better supportive care the prognosis has improved significantly with estimated 1-year mortality rates of 21% to 30% (2).
- Scolari F, Ravani P, Gaggi R etal. The Challenge of Diagnosing Atheroembolic Renal Disease. Clinical Features and Prognostic Factors. Circulation 116:298-304, 2007.
- Liew YP, Bartholomew JR. Atheromatous Embolization. Vascular Medicine 10:309-326, 2005.
- Modi KS, Rao VK. Atheroembolic Renal Disease. J Am Soc Nephrol 12:1781-1787, 2001.
- Mittal BV, Alexander MP, Rennke HG, Singh AK. Atheroembolic Renal Disease: A silent masquerader. Kidney International 73:126130, 2008.
- Lai CK, Randhawa PS. Cholesterol Embolization in Renal Allografts. A Clinicopathologic Study of 12 Cases. Am J Surg Pathol31:536-545, 2007.
Date of last revision: September 2009.