What is Atheroembolic Kidney Disease?

Atheroembolic renal disease (AERD), also referred to as cholesterol embolism or cholesterol crystal embolization, is often undiagnosed because its symptoms can overlap with many other conditions, making it difficult to distinctly identify. There’s been a rise in AERD cases with the increased use of catheter-based treatments and a higher prevalence of risk factors. Usually, its presence is suspected through a combination of factors such as an initial triggering event, kidney injury — sudden or gradual, alongside skin symptoms.

Cholesterol emboli or clots, can lead to kidney damage by blocking small kidney blood vessels, causing a lack of blood flow or ischemia. This blockage typically prompts an inflammatory reaction that can resemble vasculitis, a condition characterized by inflammation of the blood vessels, and cause the formation of large cells. These cholesterol emboli can be linked to the use of anticoagulants, vascular manipulation, or specific drug use. But there have also been instances where these emboli occur spontaneously. Depending on the severity, patients with AERD can show a range of symptoms from mild or no symptoms to severe, life-threatening conditions.

AERD is caused when small kidney arteries are blocked by cholesterol crystal emboli, released by ruptured plaques of fatty deposits in the arteries. This type of condition is considered part of a broader disease called systemic atheroembolism. Since the kidneys are located close to the abdominal aorta and receive a high blood flow, they often become the main target of cholesterol emboli. A post-mortem study found that 74% of cases with this kind of disease involved the kidneys.

What Causes Atheroembolic Kidney Disease?

Atheroembolic renal disease is a condition that occurs in people who have atherosclerotic vascular disease, a condition where plaque builds up in the arteries. These patients usually have large amounts of plaque buildup in their aorta and larger blood vessels, and this plaque consists of a fat-rich core and a thin fibrous top layer. Sometimes, physical strain or changes in blood flow can cause this top layer to rupture, releasing the fatty material into the bloodstream. This material can end up blocking blood vessels in other parts of the body.

Often, atheroembolic renal disease can result from medical procedures such as coronary artery bypass grafting, coronary stenting, abdominal aortic aneurysm repair, angiography, angioplasty, or endovascular grafting. On rare occasions, this condition can occur on its own without any triggering causes. The fatty material, or cholesterol emboli, can be released into the bloodstream without any apparent reason, after the use of specific catheters or due to certain medications. It’s important to remember that this condition can also affect a transplanted kidney and should be considered when evaluating a patient with worsening kidney transplant function.

The most common cause of atheroembolic renal disease is a procedure called coronary angiography, although it only happens in about 0.06% to 1.8% of cases. The condition can also be caused by changes in blood flow, which may account for up to 30% of cases. Cholesterol emboli can also cause damage to other body organs. Symptoms of this can include pancreatitis, gastric ulcers, and intestinal ischemia.

Atheroembolic renal disease can generally be categorized into three types:

1. An acute type that surfaces a few days after the triggering event because of a large amount of embolization.
2. A type that develops gradually or incrementally, likely due to continual embolization or inflammation of the vessels’ lining that causes additional blockage after the initial blockage. This is the most common form of the disease.
3. A chronic type that causes slow and progressive kidney function decline and is often mistaken for other kidney conditions.

In the acute type, the creatinine levels (a waste product that can be a key indicator of kidney function) will increase immediately. However, with the gradual and chronic types, the creatinine levels might not rise until days or weeks after the initial event.

Risk Factors and Frequency for Atheroembolic Kidney Disease

Atheroembolic renal disease is a condition that usually affects people who already have a disease called generalized atherosclerosis. Certain people are at higher risk, including those who are older, male, have diabetes, high blood pressure, high cholesterol, or smoke. Usually, people with this disease also have related conditions, such as heart artery disease, cerebrovascular disease, narrowed kidney arteries, weakened kidney function, aortic aneurysms, among others.

The disease’s incidence is somewhere between 1% and 5%, this variation is because the criteria for diagnosing it can change depending on the study. Though, it’s worth noting that this disease is becoming increasingly common in older adults with atherosclerosis. In fact, one study showed that 60% of people diagnosed with atheroembolic renal disease were older than 70. However, the true commonness of this disease is not clear as it’s likely often missed and therefore underdiagnosed. Most of what we know about it comes from individual case reports and smaller case series or discussions on clinicopathologic cases.

Signs and Symptoms of Atheroembolic Kidney Disease

Atheroembolic renal disease is a part of a generalized disease where fragments of cholesterol plaques break off and block the small blood vessels in various parts of your body. The most commonly affected areas include the skin, muscles of the lower extremities, digestive tract, kidneys, and brain. This disease can cause several discomforts like fever, weight loss, fatigue, and appetite loss. One might also notice visible changes on the skin, blue or purple toes, abdominal pain, sudden neurological issues like temporary blindness, mini-strokes, full-blown strokes, headaches, confusion, nerve damage, or even spinal cord infarction.

Other indications of atheroembolic renal disease include the symptoms related to kidney failure which can show up suddenly or build up over time, mild to severe protein leakage in the urine, blood in the urine, and high blood pressure. Sometimes, fragments can be seen in the eye on the retina if they originated from the ascending aorta, although it’s more common for the fragments to come from the descending aorta. Symptoms related to the skin can also signify this disease, like livedo reticularis (a purplish network pattern on the skin) and the aforementioned blue or purple toe syndrome. Additionally, swelling may occur due to such emboli.

The skin is most commonly affected outside the kidneys in such cases, with visible abnormalities in 75% to 96%. Other body parts, particularly the parts of the digestive tract close to blood vessels, can be affected as well. This can lead to abdominal pain, nausea, or vomiting. There could be Pancreas damage too, which can cause pancreatitis and its associated symptoms.

Testing for Atheroembolic Kidney Disease

A diagnosis of Acute Embolic Renal Disease (AERD) can typically be made by considering risk factors, certain triggering events, symptoms of sudden or gradual kidney failure, and signs of clots in the extremities. In some situations, a kidney biopsy may be needed to rule out other conditions like an inflammation of the blood vessels, sudden death of kidney cells, or an allergic reaction in the kidneys. This biopsy can also provide a more concrete diagnosis.

If there are visible skin changes (like glove or sock pattern discolouration, or a web-like pattern on the skin), then a skin biopsy might be a straightforward and low-risk method for diagnosing the condition. If muscle damage is suspected and a particular muscle is thought to be responsible, taking a small sample of that muscle might help confirm the diagnosis.

Another potential clue towards AERD is an increase in a special type of white blood cell called eosinophils, which is seen in about 80% of AERD cases. However, this might not be a constant finding. Other potential but not guaranteed signs of AERD are the presence of eosinophils in urine, an increase in a general inflammation marker called C-reactive peptide, and the decrease of a type of protein involved in the immune response. But keep in mind, none of these changes are exclusively linked to AERD.

Treatment Options for Atheroembolic Kidney Disease

Atheroembolic renal disease is a condition where cholesterol deposits block blood flow in the kidneys. It doesn’t have a specific cure, so the treatment mostly focuses on managing symptoms and providing comfort to the patient. Doctors generally recommend stopping blood-thinning medication and avoid or delay invasive procedures, like surgery, if possible.

Treatment usually includes the use of medications like aspirin and statins, quitting smoking, keeping blood pressure under control, and maintaining normal blood sugar levels. These strategies focus on managing atherosclerosis, a condition where fatty deposits block arteries, which is a primary cause of kidney issues. In some instances, special devices can be used during medical procedures to capture and remove these fatty deposits before they reach smaller vessels.

The aim of the treatment here is to limit tissue damage due to lack of blood supply and prevent further spread of cholesterol crystals. Avoiding substances harmful to the kidneys and limiting exposure to imaging contrast (a substance given before certain medical imaging tests) can help reduce the likelihood of this condition. Studies conducted on animals show that high levels of sugar and uric acid in the blood can worsen this kidney disease.

If the kidney function continues to deteriorate, patients may need renal replacement therapy, a medical procedure that cleans the blood when the kidneys can’t.

Using corticosteroids, medicines that reduce inflammation, is believed to lower the body’s reaction to the blocked arteries. However, the effectiveness of this method is a topic of debate. Some studies suggest that a specific dose of prednisolone, a type of corticosteroid, can bring overall improvement to patients and boost kidney health. Contrarily, other investigations suggest that these steroids may not significantly improve long-term kidney health and could even increase the risk of death.

Statins, medicines that lower cholesterol levels in the blood, might have positive effects on this kidney condition by stabilizing and reducing fatty deposits through their anti-inflammatory and cholesterol-lowering capabilities.

In severe cases where kidneys fail, patients might need dialysis, a treatment that removes waste products and excess fluid from the blood when kidneys can no longer perform these tasks.

Several conditions can have similar symptoms to acute interstitial nephritis:

Nephropathy due to contrast dye: It usually grows a day or two after being exposed to the dye. The creatinine level in the blood often goes up within a week and returns to normal in about 10 to 14 days.
AERD, which is short for atheroembolic renal disease: This condition usually starts late, often days to weeks later, and it lasts a long time. The outcome is typically poor, and it could lead to an ongoing kidney failure that might need dialysis.
Systemic vasculitis also shows symptoms in multiple parts of the body, and both it and atheroembolic renal disease can result in lower complement levels. Doctors might need to do some blood tests, a biopsy of the affected organ, or an angiogram to confirm this disease. This condition’s treatment and outcomes are quite different, so it’s crucial to diagnose it correctly.
Subacute bacterial endocarditis may also show symptoms in multiple parts of the body and result in lower complement levels. Hence, it may be mistaken for atheroembolic renal disease.
Acute interstitial nephritis: If patients show a rise in blood creatinine, mild-to-moderate proteinuria (protein in urine), hematuria (blood in urine), and eosinophilia (high eosinophil cell count in the blood), doctors might consider this condition.
The long-lasting forms of atheroembolic renal disease (AERD) might be mistaken for hypertensive nephrosclerosis (kidney damage due to high blood pressure) or ischemic nephropathy (kidney disease due to limiting blood flow to the kidneys). Subtle or missed signs on the skin can contribute to this confusion, and a kidney biopsy could be crucial to confirm the right diagnosis.

Unfortunately, these conditions can often be mistaken for each other since they present very similarly. This means doctors need to be diligent and thorough in their testing to make the right diagnosis.

What to expect with Atheroembolic Kidney Disease

AERD, or acute embolic renal disease, is often linked with irreversible damage to organs and generally has a poor prognosis. The effect on kidney function varies from patient to patient; some may need ongoing dialysis treatment, while others may see improvements, although residual kidney impairment often remains.

Renal function, or how well your kidneys are working, may improve in roughly one-third of these patients, provided they don’t experience further embolic events. Some research findings suggest that patients with AERD may regain kidney function after a long period of dialysis, longer than is generally required for other causes of end-stage kidney disease.

Bronze acute and subacute cases of AERD, approximately 30% to 55% will typically require renal replacement therapy, sometimes known as kidney dialysis. A smaller percentage, about 21% to 28%, will likely see an improvement in kidney function. Survival rates for one and two years have been observed at 87% and 75% respectively. However, the cause of death is more often related to the underlying cause of the AERD rather than the kidney disease itself. The most common cause of death among AERD patients is heart disease.

Possible Complications When Diagnosed with Atheroembolic Kidney Disease

Atheroembolic disease can cause serious problems. Some of the complications you should know about include:

Permanent damage to organs
Advanced kidney disease
Reduced blood flow to the organs
Kidney damage due to thickened and hardened blood vessels

Preventing Atheroembolic Kidney Disease

It’s really important to prevent atheroembolic renal disease, because we don’t currently have an effective treatment for it. This means taking steps to avoid the disease getting worse is key. This disease can develop more if certain medical procedures are done too often, especially in people already suffering from atherosclerosis (hardening of the arteries). So, it’s best to do things like using blood thinners, surgery, and angiography (a type of X-ray test) as little as possible.

Using newer, non-invasive ways of diagnosing, such as spiral computed tomography (a type of high-resolution imaging technique), duplex ultrasonography (an imaging technique that evaluates blood flow), and geomagnetic resonance (a method to study biological phenomena), could decrease the chance of AERD developing because of medical treatment itself (iatrogenic AERD).

It’s crucial for patients to understand their disease and how it impacts different parts of their body. If kidney replacement (renal replacement) becomes necessary, patients should undergo a complete educational program about the different types and kidney transplant options if needed. This helps patients to make informed decisions about their course of treatment.

Frequently asked questions

Atheroembolic kidney disease, also known as AERD, is a condition where small kidney arteries are blocked by cholesterol crystal emboli. This can lead to kidney damage and a lack of blood flow, causing symptoms that can range from mild to severe. AERD is often undiagnosed due to overlapping symptoms with other conditions.

The incidence of Atheroembolic Kidney Disease is somewhere between 1% and 5%.

Signs and symptoms of Atheroembolic Kidney Disease include: - Fever - Weight loss - Fatigue - Appetite loss - Visible changes on the skin - Blue or purple toes - Abdominal pain - Sudden neurological issues like temporary blindness, mini-strokes, full-blown strokes, headaches, confusion, nerve damage, or even spinal cord infarction - Symptoms related to kidney failure, such as mild to severe protein leakage in the urine, blood in the urine, and high blood pressure - Fragments seen in the eye on the retina if they originated from the ascending aorta - Livedo reticularis (a purplish network pattern on the skin) - Swelling due to emboli - Abnormalities in the skin outside the kidneys in 75% to 96% of cases - Digestive tract symptoms like abdominal pain, nausea, or vomiting - Pancreas damage leading to pancreatitis and associated symptoms.

Atheroembolic renal disease can occur in people who have atherosclerotic vascular disease, where plaque builds up in the arteries. It can also result from medical procedures such as coronary artery bypass grafting, coronary stenting, abdominal aortic aneurysm repair, angiography, angioplasty, or endovascular grafting. In rare cases, it can occur on its own without any triggering causes.

Nephropathy due to contrast dye, Systemic vasculitis, Subacute bacterial endocarditis, Acute interstitial nephritis, Hypertensive nephrosclerosis, and Ischemic nephropathy.

The types of tests that may be needed to diagnose Atheroembolic Kidney Disease (AERD) include: - Kidney biopsy to rule out other conditions and provide a concrete diagnosis - Skin biopsy if there are visible skin changes - Muscle biopsy if muscle damage is suspected - Blood tests to check for an increase in eosinophils, C-reactive peptide, and a decrease in a type of protein involved in the immune response - Urine test to check for the presence of eosinophils in urine It is important to note that these tests are not exclusively linked to AERD and may be used to rule out other conditions as well.

Atheroembolic Kidney Disease is treated by managing symptoms and providing comfort to the patient. Treatment includes the use of medications like aspirin and statins, quitting smoking, controlling blood pressure and blood sugar levels, and avoiding substances harmful to the kidneys. Special devices can be used during medical procedures to capture and remove fatty deposits. If kidney function continues to deteriorate, renal replacement therapy may be necessary. The use of corticosteroids to reduce inflammation is debated, as some studies suggest improvement while others suggest potential risks. Statins may have positive effects by stabilizing and reducing fatty deposits. In severe cases, dialysis may be needed.

When treating Atheroembolic Kidney Disease, there can be side effects such as: - The effectiveness of corticosteroids in improving kidney health is a topic of debate, with some studies suggesting improvement and others suggesting no significant long-term improvement and even an increased risk of death. - Statins, while they may have positive effects on this kidney condition by stabilizing and reducing fatty deposits, can also have side effects such as muscle pain, liver damage, and digestive issues. - In severe cases where the kidneys fail, patients may need dialysis, which can have its own complications and side effects. - The disease itself can cause serious problems, including permanent organ damage, advanced kidney disease, reduced blood flow to the organs, and kidney damage due to thickened and hardened blood vessels.

The prognosis for Atheroembolic Kidney Disease (AERD) varies depending on the individual and the severity of the disease. Here are the key points regarding the prognosis: - AERD is often linked with irreversible damage to organs and generally has a poor prognosis. - The effect on kidney function varies from patient to patient; some may need ongoing dialysis treatment, while others may see improvements, although residual kidney impairment often remains. - Roughly one-third of patients may experience an improvement in renal function, provided they don't experience further embolic events. - Approximately 30% to 55% of acute and subacute cases may require renal replacement therapy (kidney dialysis), while about 21% to 28% may see an improvement in kidney function. - Survival rates for one and two years have been observed at 87% and 75% respectively, but the cause of death is more often related to the underlying cause of AERD rather than the kidney disease itself. The most common cause of death among AERD patients is heart disease.

A nephrologist.

Blood Cholesterol Management Chronic Kidney Disease Kidney Health Renal Failure