Atheroembolic renal disease is caused by occlusion of small arteries in the kidneys by cholesterol crystal emboli from ulcerated atherosclerotic plaques and is a part of systemic atheroembolism disease. The proximity of the kidneys to the abdominal aorta and high renal blood flow make them the most frequent target organ.
Atheroembolic renal disease occurs in patients with atherosclerotic vascular, and typically these patients have significant atherosclerotic plaques particularly in the aorta and large to medium-sized vessels. These plaques have a lipid-rich core and thin fibrous cap. Mechanical and hemodynamic stresses can rupture the fibrous cap and release the underlying extracellular cholesterol-rich matrix, which enters circulation and eventually lodges a distal site causing vascular occlusion.
It is frequently an iatrogenic disease and may follow surgical procedures like coronary artery bypass grafting, abdominal aortic aneurysm repair, and vascular procedures like angiography, angioplasty or endovascular grafting, may be related to anticoagulation with warfarin, heparin, and antiplatelet agents or to thrombolytic therapy. In a small number of patients, atheroembolic renal disease may occur spontaneously without any inciting or triggering factors.
Atheroembolic renal disease occurs in patients with systemic generalized atherosclerosis. Risk factors include older age, male gender, diabetes, hypertension, hyperlipidemia, and smoking. These patients frequently have coronary artery disease, congestive heart failure, cerebrovascular disease, renal artery stenosis, renal insufficiency, aortic aneurysm, or other similar atherosclerotic diseases.
During surgical procedures, mechanical trauma (incision, clamping, or manipulation of the vessel) may disrupt the atherosclerotic plaques. During angiography or angioplasty, catheter manipulations disrupt the plaques, exposing the soft, cholesterol-laden core of the plaque to the arterial circulation. Anticoagulants or thrombolytic therapy prevent the formation of a protective thrombus overlying an ulcerated plaque or could initiate the disruption of a plaque by causing hemorrhage into it exposing them to the hemodynamic stress of circulating blood. Once in the circulation, cholesterol crystal emboli lodge in small arteries, 150 to 200 mm in diameter. These cause partial occlusion of the vessel and distal ischemia. This is followed by an inflammatory reaction, intimal proliferation, and intravascular fibrosis. The entire process results in the further obliteration of the lumen and more ischemic changes.
In the kidney, emboli typically lodge in the arcuate and interlobar arteries and are seen on light microscopy as elongated biconvex transparent needle-shaped clefts. These clefts represent the cholesterol crystals that are dissolved during tissue processing. Initially, the blood vessel is partially occluded initially. Endothelial inflammatory response ensues and eventually leads to complete obliteration of flow of blood within weeks or months.
Glomeruli may appear normal in initial stages, but eventually, there may be glomerular collapse or shrinkage. Other changes in histology may include acute tubular necrosis, interstitial fibrosis, and tubular atrophy.
Atheroembolic renal disease is most commonly part of generalized atheroembolic disease, and the 5 most commonly affected organs are skin, lower extremity skeletal muscles, gastrointestinal tract, kidneys, and brain. Clinical manifestations include livedo reticularis, blue toe/purple toe syndrome, abdominal pain and neurological deficits. AERD presents with acute/subacute/chronic renal failure, mild to moderate degree of proteinuria, hematuria, accelerated hypertension or new onset of hypertension. Eosinophilia, eosinophiluria, and hypocomplementemia are known to occur in this disease.
There are 3 forms of atheroembolic renal disease:
The combination of risk factors, inciting or triggering event, acute/subacute renal failure, and signs of peripheral emboli strongly suggest the diagnosis. In the presence of these, the diagnosis of atheroembolic renal disease can be made without doing a kidney biopsy. Renal biopsy, however, may be required in some cases to exclude vasculitis, ATN, allergic interstitial nephritis, etc. and may provide a definite diagnosis.
A skin biopsy may be a simple and minimally invasive way of making the diagnosis if there are skin lesions (digital infarcts, livedo reticularis). In the presence of muscle damage and if a specific muscle can be identified, muscle biopsy may be another minimally invasive way to establish the diagnosis.
There is no specific therapy for atheroembolic renal disease and treatment is mostly symptomatic and supportive. Dialysis may be appropriate if there is no evidence of continued embolic events. Anticoagulation should be discontinued, and performance of more invasive diagnostic/therapeutic vascular procedures or surgery should be avoided or delayed, if possible. Treatment with aspirin and statins, smoking cessation, blood pressure control, and glycemic control should be provided for management of atherosclerosis. Distal protection vascular devices are being used in interventional procedures to prevent embolic material from lodging in distal sites.
In contrast nephropathy, an increase in serum creatinine starts a day or two after exposure to contrast, serum creatinine peaks in approximately one week and returns to baseline within 10 to 14 days. On the other hand, AERD frequently has a delayed onset, usually days to weeks, and a protracted course. The outcome is often poor, resulting in progressive renal failure requiring dialysis.
Systemic vasculitis is another consideration since there is multisystem involvement and decrease in complement levels in both atheroembolic renal disease and systemic vasculitis. Serological testing, biopsy of affected organ or angiography may be needed to rule this disease out since management and outcome of vasculitis is very different. Subacute bacterial endocarditis may also enter into differential diagnosis due to multisystem manifestations and low complement levels. Rising serum creatinine, mild to moderate degree of proteinuria, hematuria, and eosinophilia may also raise the possibility of acute interstitial nephritis.
Chronic forms of atheroembolic renal disease may be mistaken for hypertensive nephrosclerosis or ischemic nephropathy if peripheral manifestations are not obvious or missed. Renal biopsy may be crucial in these cases to make the diagnosis.
Atheroembolic renal disease is associated with poor renal and patient survival. The cause of death is usually multi-organ failure, visceral ischemic disease or cardiovascular disease rather than end-stage kidney failure. Thirty percent of patients require dialysis, and some of them may end up on long-term dialysis. Renal function may improve in approximately one-third of these patients after variable time if there are no more embolic events and tubular recovery ensues.
Atheroembolic renal disease is frequently an iatrogenic disease and may follow surgical procedures, angiography, angioplasty or endovascular grafting, may be related to anticoagulation or thrombolytic therapy and presents with acute/subacute/chronic renal failure, mild to moderate degree of proteinuria, hematuria, accelerated hypertension or new onset of hypertension. Differential diagnosis includes contrast nephropathy, allergic interstitial nephritis, acute tubular necrosis. Renal and patient survival are poor and related to a coexistent significant cardiovascular disease.