What is a Cholesterol Embolism?

Small renal arterial embolism can cause varying degrees of renal impairment, but most have progressive decline in renal function until end-stage renal disease. Unexplained renal failure with recent hypertension or worsening hypertension is a common clinical manifestation. Renal damage from cholesterol embolism can also manifest as proteinuria and even nephrotic syndrome. Pathology can be manifested as focal segmental glomerulosclerosis. Therefore, elderly patients with arterial vascular disease should consider renal arterial cholesterol embolism if they develop progressive renal insufficiency and nephrotic syndrome.

Cholesterol embolic nephropathy

Cholesterol embolic nephropathy is a type of atherosclerotic disease in the elderly kidney. It originates from cholesterol crystals in atherosclerotic plaque fragments. It mainly invades the renal artery opening or proximal end and forms obstruction, cone-shaped narrowness, and eccentric Stenosis, secondary expansion after stenosis, and calcification, can be seen in unilateral or bilateral lesions. Can cause renal insufficiency, renal atrophy, decreased renal function, renal vascular hypertension, etc., often coexisting with occlusive arterial diseases such as fundus, limbs, heart, brain.

Overview of cholesterol embolic nephropathy

Glomerular lesions caused by cholesterol embolism are often diverse, and there is evidence of ischemia, such as glomerular capillaries, shrinkage, and enlargement of the glomerular cavity; intermittent glomerular basement membrane (GBM) thickening is also seen.

Classification of cholesterol-embolizing nephropathy

Geriatrics

Clinical manifestations of cholesterol embolizing nephropathy

Cholesterol embolism is common in men, especially those over 60 years of age. Patients often have severe atherosclerosis of the aorta and its branches. Clinically, hypertension, peripheral vascular and cerebrovascular diseases, myocardial infarction and renal function Incomplete and aortic aneurysms. Because of the number, size, and emboli of different cholesterol emboli, the clinical manifestations vary in severity, and most of them are ignored. Generally speaking, if elderly patients with arterial vascular disease develop progressive renal insufficiency, considering the possibility of ischemic renal disease, it should be considered that secondary renal artery stenosis, renal cholesterol embolism or both . Small renal arterial embolism can cause varying degrees of renal impairment and most have progressive decline in renal function until end-stage renal disease. Unexplained renal failure with recent hypertension or worsening hypertension is a common clinical manifestation. Clinically, there are often systemic obvious atherosclerotic lesions, such as a history of myocardial infarction, stroke, and peripheral vascular disease. When a large number of cholesterol crystals suddenly embolize the renal arterioles extensively, the clinical manifestations are acute renal failure. If it is a small amount of repeated embolism, renal insufficiency progresses slowly, clinically there is hypertension, proteinuria, and a small amount of red blood cells and white blood cells in urine. Cholesterol-induced cirrhosis does not cause renal infarction. Clinical diagnosis is very difficult, and renal arteriography does not help diagnosis. Renal biopsy or autopsy is helpful for diagnosis. The main pathological manifestations are the interlobular arteries, arcuate arteries, and interlobe arteries in the affected area. Cholesterol crystals can be formed to form a blank area. Reactive hyperplasia of vascular wall cells, glomerular hyaline degeneration, and tubules Shrink. The above-mentioned changes were not seen in the unaffected area. Cholesterol embolism may also be present in extrarenal tissues (such as cholesterol cirrhosis in the retina and evidence of cholesterol embolism in muscle or extremity tissue biopsy), which can help indirect diagnosis. ^[1]

Cholesterol embolism nephropathy symptoms and signs

(A) manifestations of kidney involvement

The kidney is the most common target organ for cholesterol crystal embolism, but only about 50% show clinical symptoms. Renal symptoms appear at different intervals after the inducing event. Some patients may develop symptoms quickly, while others may be insidious, being several weeks to several months late, with an average interval of 5.3 weeks between inducing events and diagnosis of kidney disease.

Cholesterol crystal emboli can cause kidney damage. Some patients have only mild to moderate renal impairment. In severe cases, dialysis therapy is needed. Atherosclerosis embolism kidney disease mostly manifests in the following three situations: sudden acute renal failure: often accompanied by evidence of cholesterol crystal embolism in other parts, mostly onset a few days after the induced event; subacute kidney injury: may be related to The allergic reaction induced by cholesterol crystal embolism is related to the new generation of cholesterol crystal embolism. Kidney damage progresses gradually, serum creatinine gradually increases within a few weeks, and some patients may develop embolism based on chronic kidney disease. Chronic kidney damage with renal vascular sclerosis and / or ischemic kidney disease: Usually asymptomatic, cholesterol crystal embolism is only found in renal biopsy or autopsy, and it is often easy to misdiagnose.

Most patients have continued deterioration of renal function or rely on dialysis. Renal function can be improved or even recovered in some patients, but chronic kidney injury remains. Appeared as acute renal failure and chronic cases in 28 to 61% of patients dependent on dialysis. In early case reports, patients usually progress to end-stage renal failure within weeks to months. However, recent studies have suggested that spontaneous recovery of renal function can reach up to one third, and can even occur at different stages of dialysis treatment. The recovery of renal function may result from the following factors: such as the resolution of the inflammatory response, the recovery of renal tubular necrosis at the ischemic site, and the effective compensation of the remaining nephrons.

Urine tests are often found abnormally but are not specific. About half of the patients have mild proteinuria, and a few have nephropathy-range proteinuria. Urinary sediment can have red blood cells, white blood cells, and granular casts, and some patients have eosinophils.

60 to 100% have high blood pressure and are difficult to control. Sometimes they can show malignant hypertension, which may be caused by excessive activation of the renin angiotensin system.

(B) manifestations of extrarenal involvement

1. There are many signs and symptoms of skin involvement. It can occur suddenly or gradually, and new cholesterol crystal embolism can occur again. Skin abnormalities are more common, up to 35% to 50%. Typical skin lesions include reticulated plaques (lower extremities, buttocks, and abdominal wall); nail bed infarction; toe gangrene, ulcers, and blue-purple spots, also known as "blue-toe" syndrome, with extremely specific manifestations of cholesterol crystal embolism syndrome ; Skin nodules, purpura and petechiae, common in both lower extremities and distal. In severe cases, scrotal and penile necrosis can occur.

2. The incidence of gastrointestinal tract is about 18 to 48%. Gastrointestinal bleeding caused by mucosal ulcers or infarctions is more common and can also manifest as diarrhea, intestinal obstruction, abdominal pain after eating and small bowel perforation. Pancreatitis, cholecystitis, and splenic infarction have also been reported.

3. Symptoms of musculoskeletal involvement include muscle pain, joint pain, and sometimes rhabdomyolysis.

4. The central nervous system is often manifested as mental disorders, headaches, local neurological disorders and transient dark haze. Sudden cerebrovascular accidents, paresis in the lower limbs, mononeuropathy, and retinal artery occlusion can cause retinal infarction, also known as Hollenhorst sign, which are additional diagnostic features of the disease.

5. Pulmonary involvement has been reported in a few other cases with clinical hemoptysis and difficulty breathing. There may also be subclinical involvement of the thyroid gland and necrosis of the femoral head. Other non-specific manifestations include hypothermia and weight loss.

Cholesterol embolism nephropathy pathophysiology

The more severe the atheroma, the greater the risk of cholesterol embolizing kidney disease. Cholesterol embolism kidney disease has been reported in about 1% of patients with mild aortic disease, and up to 15% -30% of patients with severe aortic disease. Although cholesterol crystal emboli can be spontaneously shed from the aorta, most reports of the occurrence of cholesterol embolizing kidney disease are closely related to the application of invasive or interventional cardiovascular diagnostic and treatment techniques, including aortic and cardiac surgery, aortic angiography, heart Intubation, percutaneous coronary or renal angioplasty, others include intra-aortic balloon compression, cardiopulmonary resuscitation. In most cases, intra-arterial atherosclerotic lesions are aggravated or damaged during catheter operation, leading to atheromatous plaque dislocation and embolization of the kidneys, skin, and other organs.

In addition, cellulose thrombosis at the site of plaque rupture in the aortic atherosclerosis due to influencing or intervening treatment is also prone to cause renal embolism. Intravenous application of streptokinase in the treatment of pulmonary embolism and acute myocardial infarction can also cause secondary cholesterol embolism and must be paid great attention. Renal pathology Cholesterol embolism nephropathy occurs predominantly in older people over 60 years of age. The disease is caused by the shedding of fragments of atherosclerotic plaque. The cholesterol crystals in the film can block the small arteries (150-250 m in diameter) of deep crops and other organs (retina, brain, pancreas, muscle and skin), and stimulate them. Vessel wall cells regenerate and eventually cause vascular lumen occlusion, aortic and renal arterial occlusion. Aortic and renal arterial surgery, arterial catheterization, and excessive anticoagulation can all cause atherosclerotic plaque fragments to fall off, and they can also spontaneously fragment and fall off.

Light microscopy revealed renal vascular and glomerular lesions. The arterial lumen is more occluded and contains cellular components, which mainly include tissue macrophages, very few lymphocytes and polymorphonuclear leukocytes. Individuals can see artificial artifacts caused by cholesterol crystals, which appear as slender crystal-shaped spaces. This is because cholesterol is dissolved or shed by organic solvents during tissue fixation. Electron microscopy sections can retain lipid components due to different processing methods.

Glomerular lesions caused by cholesterol embolism are often diverse, and evidence of ischemia is often seen. Such as the glomerular capillaries shrink and shrink, the glomerular cavity is enlarged, or intermittent glomerular basement membrane (GBM) thickening can be seen. However, the electron microscope confirmed that the thickness of the GBM was normal. What the light microscope saw was caused by the significant spiral curl of the GBM. However, this kind of GBM is not unique to cholesterol embolism, but a typical manifestation of ischemic renal damage. Chronic glomerular lesions are vitreous deformation and global sclerosis, and corresponding interstitial fibrosis and mononuclear cell infiltration can be seen in late stages. Recent reports suggest that glomerular lesions caused by cholesterol embolism can also manifest as focal segmental glomerulosclerosis.

Immunopathology showed that 1gM and C3 coarse particles were deposited on the hardened glomeruli. Electron microscopy confirmed the irregular spiral curl of GBM.

Cholesterol embolism nephropathy

Laboratory tests: No positive urine routine findings. Recently, some patients may have proteinuria, and in severe cases, they can reach the level of nephrotic syndrome. Microscopic examination of urine sediment revealed red and white blood cells, occasionally transparent and granular casts, and severe hematuria with gross hematuria. Elevated peripheral blood leukocytes and blood clots are common. Transient peripheral eosinophilia has certain diagnostic significance for atherosclerosis-related embolic kidney disease, and some people believe that the incidence can reach 80%.

Cholesterol embolism nephropathy treatment options

There is currently no effective treatment for cholesterol embolism syndrome. Renal failure can be treated with dialysis therapy, hypertension can be appropriately controlled with blood vessel content and treated with antihypertensive drugs. Accelerated hypertension in patients with cholesterol embolism is often associated with angiotensin , such as the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists should be particularly careful. Because the two can further aggravate renal function damage in the relatively narrow renal artery, aging and / or renal ischemia, steroid hormones have been clinically tried to reduce inflammatory damage, but with little effect. Platelet inhibitors, vasodilators, and low-molecular dextran were all ineffective.

It is currently believed that anticoagulants can worsen the condition and avoid its use. Recently, some people successfully applied statin lipid-lowering drugs to partially restore the tadpole function in one patient, but further research is needed. Once the disease is suspected or confirmed, the use of anticoagulants should be avoided or discontinued, and further cardiovascular examination and treatment should be avoided. Hypertension should be strictly controlled. Sympathetic nerve activity can relieve transient pain and improve local blood circulation in some patients with lower limb ischemia. Application of vasodilator drugs and hemofiltration to treat heart failure and strengthen nutritional support. For patients with abdominal aorta falling off cholesterol emboli repeatedly, surgical treatment may be considered if necessary. If the patient also has renal artery stenosis, you can also maintain dialysis for several months to stabilize renal function, and then perform renal artery bypass surgery or place a stent.