Microalbuminuria

What is Microalbuminuria?

Albumin, a substance produced by our liver cells, plays several important roles in our body. This includes maintaining a healthy pressure balance in our blood vessels, providing nutrients for certain kidney cells, and acting as an antioxidant to protect our cells from damage. The liver typically produces around 10-15 grams of albumin each day, which gets carefully regulated by various factors in our body. Roughly 4.5% of it leaves the blood every hour and is recaptured by our lymphatic system, which is part of our immune system.

When albumin travels through our kidneys, it typically doesn’t pass through the kidney’s filtration system. This is because both albumin and kidney cells carry a negative charge, making them repel each other. Furthermore, the kidney’s filtration system has tiny openings that are usually too small for albumin to pass. Another factor that restricts albumin is a complex in the kidney that breaks it down to conserve amino acids for later use.

However, if a person has a condition that affects the kidney’s filtration system, albumin can end up in urine. The amount of albumin present in urine is medically significant. “Microalbuminuria” is a term used when the amount of albumin in urine is higher than normal, but not high enough to be detected by a standard urine test. This typically refers to a rate of between 30 to 300 milligrams of albumin being excreted in the urine every 24 hours. If this level rises above 300 milligrams in 24 hours or exceeds 100 milligrams in 12 hours, it is termed “macroalbuminuria”. These signs, along with a condition called diabetic retinopathy and the absence of other kidney diseases, could point towards diabetic kidney disease in a person with type 1 or 2 diabetes.

The measure of albumin in urine is also often expressed as a ratio to another substance, creatinine. This gives us the Urinary Albumin-to-Creatinine Ratio (UACR), which can provide a more accurate measure as it accounts for urine concentration and volume. However, many factors can affect this ratio. These include gender, race, blood pressure, time of day, muscle mass, as well as intake of food, water, and salt. Therefore, UACR can vary significantly from day to day and person to person. For an accurate measure, doctors recommend taking three UACR measurements, each a month apart.

What Causes Microalbuminuria?

Microalbuminuria happens when the glomerular basement membrane (GBM, a part of your kidney) doesn’t function correctly—allowing albumin (a type of protein) to enter your urine. This issue often arises because the N-deacetylase enzyme, responsible for forming heparan sulfate (contributing to GBM’s negative charge), becomes less effective under ill-managed blood sugar. This problem further dilutes GBM’s negative charge, leading to an excessive leakage of albumin. Similarly, advanced glycosylation end-products can nullify the negative charge of albumin, making it easier for albumin to mix with GBM and mesangial matrix proteins. High blood sugar can trigger the glycation of GBM and podocyte receptors, which can also alter the charge on GBM.

The ‘Steno hypothesis’ suggests that problems with the systemic vascular endothelial (the inner layer of blood vessels) can set off microalbuminuria and cardiovascular disease. This theory stems from the notable connection between these three conditions. Therefore, health issues causing damage to the endothelial are viewed as risk factors. They encompass ageing, insulin resistance, abnormal lipid levels (dyslipidemia), obesity, high blood pressure, lack of physical activity, and smoking. Some research studies suggest a genetic link between microalbuminuria, atherosclerosis (hardening and narrowing of arteries), and nephropathy (kidney damage). A deletion-deletion polymorphism of the ACE gene was found amongst patients with a high rate of UAE, indicating a genetic component.

Risk Factors and Frequency for Microalbuminuria

Microalbuminuria, a condition often found in patients with diabetes and hypertension, affects a significant portion of the population. It’s an issue particularly common among adults over 40, and the likelihood increases with age. In a study of over 22,000 individuals ranging from 6 to 80 years old, 7.8% overall had this condition. Women are more likely to be affected, with a prevalence of 9.7%, compared to 6.1% in men.

• In people between the ages of 20 and 49, the rate of microalbuminuria was 5.8%.
• It increases to 11.4% in people aged between 50 and 69.
• In people aged over 70, the rate rises even higher to 22.7%.

Looking at diabetes patients specifically, microalbuminuria is also a common issue. For those with type 1 diabetes, about 6% will have this condition in the first three years following their diagnosis, but after five years, that number jumps to 41%. For those with type 2 diabetes, the prevalence fluctuates between 20 and 25%, regardless of how recently they were diagnosed.

When it comes to uncontrolled hypertension patients, almost half (47.4%) will experience microalbuminuria. Those who have their blood pressure under control still have a significant risk, with the rate sitting at 36.7%.

Signs and Symptoms of Microalbuminuria

Microalbuminuria is a condition where small amounts of a protein called albumin are found in the urine. It often doesn’t cause any noticeable symptoms. However, it’s often linked with diseases like diabetes, obesity and high blood pressure so if it’s detected in a patient, healthcare providers need to look for signs of these conditions. They might do this by checking the patient’s personal and family health history and looking for signs of kidney, heart, and systemic diseases. They might also look for symptoms associated with diabetes, including heart disease, vision problems, and urinary issues. It’s also important to check blood pressure, check for any heart abnormalities, listen for carotid artery sounds, and look for swelling in the lower legs.

Microalbuminuria is often discovered during routine health check-ups or when testing for diseases like diabetes or high blood pressure. It is usually not linked with serious kidney diseases. When it’s detected, health professionals should consider more common reasons before jumping to serious conclusions. They might ask some of the following questions:

• Did the patient recently do intense physical activity or have a fever?
• Is the patient under 30 or a tall, thin adolescent with severe lordosis (curvature of the spine)?
• Is the patient dealing with non-kidney-related health issues such as severe heart failure or sleep apnea?
• Does the patient show symptoms of a serious kidney disease or significant glomerular pathology (problems with the filtering units in the kidney)?
• Has the urine’s appearance changed, is it red/smoky, frothy, and is this associated with respiratory infection?
• Is there any swelling in the patient’s ankles, around the eyes, lips, or scrotum?
• Has the patient been diagnosed with high blood pressure or high cholesterol?
• Has the patient been diagnosed with a multisystem disease or glomerulopathy?
• Does the patient, or their family, have a history of kidney disease?
• If the patient has diabetes, how long have they had it, and are there any complications like eye issues?
• Does the patient’s family have a history of diabetic kidney disease?
• Does the patient have any systemic inflammatory diseases like lupus or rheumatoid arthritis?
• Is the patient experiencing other symptoms like joint pain, skin rash, bone pain, fever, weight loss, night sweats, or Raynaud’s syndrome?
• Is the patient taking any medication, including herbal remedies?
• Does the patient have a history of certain illnesses like jaundice, malaria, tuberculosis, syphilis, or endocarditis?
• Is the patient at risk for HIV infection or hepatitis?

During the physical examination, healthcare providers should assess the patient’s intravascular volume status. They might do this by checking blood pressure and pulse while the patient is standing and lying down, examining the jugular venous pulse, and listening to heart sounds. They might also look for signs of edema or swelling, which isn’t always present with microalbuminuria. But if the protein loss is significant, the patient might have gained weight and developed fluid buildup in their lungs. Additionally, they should look for systemic features and signs of protein loss complications.

Testing for Microalbuminuria

The best test for detecting microalbuminuria, which refers to tiny amounts of a protein called albumin in the urine, is a 24-hour urine collection. This test yields the most reliable results, but it does require effort and time. The urine albumin-to-creatinine ratio (UACR) test adjusts for urine concentration and volume, but results can vary due to other factors. The urine spot collection changes depending on the urine amount. Other tests that have similar reliability to a 24-hour collection have been developed, including immunoturbidimetry, immunonephelometry, and various types of immunoassays.

The National Kidney Foundation and the European Society of Hypertension advise that high-risk patients should have a UACR screening test for microalbuminuria and potential complications. This includes the elderly, African Americans, Asians, patients with diabetes or high blood pressure, and patients with a family history of chronic kidney disease developed after the age of 60. However, whether it’s beneficial to screen the general population is still being evaluated.

The American Diabetes Association recommends that people with type 1 diabetes, if they’ve had it for more than five years, be screened yearly. Similarly, patients with type 2 diabetes and diabetic kidney damage should also have this screening yearly, starting immediately after their initial diagnosis.

Medical professionals should conduct tests including a metabolic panel (to check for decreased filter rate of kidneys, increased levels of waste products in the blood, and electrocyte imbalances) and a white blood cell count (for potential inflammation). Other blood tests may be required to assess related conditions, like blood sugar, hemoglobin A1c, lipid panel, and heart enzymes tests. An ultrasound can also be performed to detect any kidney or urinary abnormalities.

Patients with any kidney dysfunction or signs of glomerular disorders, abnormalities in the tiny blood vessels in the kidneys, should see a kidney specialist. The urine dipstick test mainly detects albumin. Some factors can lead to false-positive results, such as recent use of an iodine-based contrast dye, visible blood in the urine, and alkaline urine. Normally, there should be less than 150 mg of protein in urine per day.

An early morning spot protein test or a urinary albumin-to-creatinine ratio test can be done to screen for microalbuminuria. If a large amount of protein is detected, a 24-hour urine collection must be done. These tests can also be used for follow-up.

Sometimes protein in the urine can be temporary. To verify whether this is the case, doctors will perform repeated tests on separate occasions, in different conditions, and before any physical activity. If the cause is believed to be orthostatic proteinuria, a condition where protein is present in the urine in larger amounts when standing upright, the doctor will collect urine samples at different times of the day and night.

To identify the underlying disease causing the albuminuria, doctors can conduct a series of tests, including an autoantibody panel that tests for specific antibodies commonly found in autoimmune diseases.

Imaging tests may also be conducted, like renal ultrasonography, which could help detect any glomerular disease. Chest X-rays or CT scans might be necessary depending on the overall patient situation.

Treatment Options for Microalbuminuria

If you have microalbuminuria, it means that there are small amounts of a protein called albumin in your urine – a sign that your kidneys may not be functioning correctly. In response to this, doctors will often recommend a number of treatments aimed at reducing the chances of other health problems, particularly heart-related ones.

The first step is to adopt healthy lifestyle habits to better control both diabetes and high blood pressure. While this may sound like a simple solution, it has been shown to help save retinal (eye) function, prevent further damage to the kidneys, decrease the risk of strokes and reduce small blood vessel complications. It may be surprising, but some studies even suggest that swapping red meat for chicken could reduce the amount albumin found in urine by 46%. This dietary shift, coupled with a normal protein diet, can also lead to decreases in total cholesterol.

Maintaining a blood sugar level (A1c) of less than 7% can help to lower the risk of having albumin in your urine. Certain medications like insulin and a drug called rosiglitazone can be helpful in achieving this. Additionally, medications like ACE inhibitors and angiotensin receptor blockers (ARBs) or vasodilatory beta-blockers can help reduce high blood pressure. ACE inhibitors can even be beneficial for diabetic patients without high blood pressure as they help protect the kidneys from damage.

If controlling protein in your urine remains a challenge, additional drugs such as spironolactone, eplerenone, or a newer medication called finerenone may be added to your treatment plan. However, with these medications, there’s a risk of too much potassium build-up in your body. If needed, immunosuppressants like cyclophosphamide and azathioprine can also be considered, especially when kidney function is continuing to get worse or if vasculitic changes (inflammations of blood vessels) are observed in a kidney biopsy.

Some other experimental drugs are also showing promise in dealing with microalbuminuria. These work by reducing protein glycation, a process linked to many of the long-term complications of diabetes. Medications like thiamine, ALT-711, pimagedine, and ruboxistaurin are some examples. Other substances like glycosaminoglycans (for example, a drug named sulodexide) have demonstrated a capacity to decrease albuminuria. Statins, which are typically prescribed to lower cholesterol levels, may also help with this, although more research is required to confirm the finding.

Additional measures like weight loss, use of aspirin, maintaining low levels of LDL cholesterol (often known as the bad cholesterol), and certain new diabetes medications (like canagliflozin and empagliflozin) that also help reduce albumin in urine can be used. Non-dihydropyridine calcium channel blockers, a type of blood pressure medication (such as diltiazem and verapamil), are found to be more helpful in decreasing protein in urine than other types of calcium channel blockers.

Finally, the amount of microalbumin in your urine can also serve as a way to gauge how well the treatment is working, especially if you have high insulin levels, insulin resistance, and high blood pressure.

What else can Microalbuminuria be?

Microalbuminuria, which is an abnormal amount of albumin in the urine, is seen in many different diseases, including those related to the kidneys and those not related to the kidneys. It’s been suggested that this condition can flare up during periods of bodily inflammation. Some examples of this inflammation include:

• Periodontitis (gum disease)
• Obstructive respiratory disease (like asthma or COPD)
• Hepatitis (a liver disease)
• Bowel disease
• Pancreatitis (inflammation of the pancreas)
• Rheumatoid arthritis (an autoimmune disease affecting joints)
• Psoriasis (a skin condition)
• Ischemic conditions (where blood supply to tissues is reduced)
• Reperfusion (the restoration of blood flow after ischemia)
• Burns
• Trauma
• Sepsis (a life-threatening response to infection)
• Surgery

Additionally, an increased amount of toll-like receptor 4 – a key part of our immune system – has been linked to both microalbuminuria and diabetic kidney disease. Therefore, it’s believed that inflammation may play a big role in the progression of these diseases.

Interestingly, if microalbuminuria is found in a woman during the third trimester of her pregnancy, it could be a sign of pre-eclampsia, a potentially serious pregnancy complication, in the future.

What to expect with Microalbuminuria

The main reason for checking the level of UAE (Urinary Albumin Excretion) is to understand if a patient might face complications in the future. But, UAE should not only be seen as a sign of kidney damage. It can also predict if kidney problems are likely to get worse and if there are any systemic disorders affecting the kidneys.

The Glomerular Filtration Rate (GFR) – which measures how well your kidneys are cleaning your blood – is a well-known way to assess how severe chronic kidney disease is. When comparing GFR to UAE, you could say GFR is a direct indicator of kidney damage. Studies have shown that there’s a strong association between having higher than normal UAE and developing serious kidney disease. If a patient has low GFR, possibly indicating stage 3 or 4 kidney disease, and also has high levels of UAE, they should be seen as very high risk rather than just high risk, as per the GFR. This categorization helps make sure that swift action is taken to prevent more severe complications such as macroalbuminuria, diabetic kidney disease, proteinuria, and chronic kidney disease.

Also, having high levels of UAE is associated with a higher chance of developing cardiovascular problems, like heart disease, stroke, and peripheral vascular disease, which can increase the risk of sickness and death. For adults, the risk increases four to six times, and for people with diabetes, it doubles. The risk is even higher for patients who have macroalbuminuria, or large amounts of protein in the urine. Therefore, regular testing and treatment of high UAE could prevent the development of macroalbuminuria and possibly even prevent death. The risk of these complications can start increasing even if UAE is only slightly above normal.

In patients with essential hypertension (high blood pressure), high levels of UAE can predict a decrease in kidney function, blocked coronary arteries, and hypertensive retinopathy, a condition that can damage the retinas of the eyes. However, the latter two condition can be reversed if appropriate treatment is given in time.

Possible Complications When Diagnosed with Microalbuminuria

As the disease progresses, patients can develop macroalbuminuria, a kidney condition related to diabetes, and proteinuria, a condition where there is an abnormal amount of protein in the urine. A blood test for albumin, a type of protein, doesn’t help determine the nutritional status of a patient. However, in cases of extreme starvation, albumin levels decrease in the blood but increase in the urine.

Possible complications of proteinuria include:

• Fluid overload leading to pulmonary edema, a condition where fluid accumulates in the lungs
• Acute kidney injury due to reduced blood volume and worsening of kidney disease
• Higher chances of getting cardiovascular diseases
• Increased likelihood of vascular thromboses, such as blockages in kidney veins
• Greater vulnerability to bacterial infections

Preventing Microalbuminuria

When dealing with a kidney condition known as microalbuminuria, the patient’s involvement and understanding are vital. They need to stick to regular check-ups, adhere to guidelines for screening tests, make necessary lifestyle changes, and consistently take their prescribed medication.

If the doctor advises to testing the urine for a full 24 hours, it’s important that the patient understands the method for collecting the urine sample. Written instructions should be provided for clarity. Patients should also be informed about possible side effects of certain medications often used to treat the condition. These medications, called ARBs (Angiotensin II receptor blockers) and ACE (Angiotensin-converting enzyme) inhibitors, may cause side effects such as swelling under the skin (angioedema), cough, dizziness, fainting (syncope), high levels of potassium in the blood (hyperkalemia), low blood pressure (hypotension), and a small increased risk of lung cancer.