A/G Ratio: Conditions Linked to High or Low Albumin/Globulin Levels

The A/G ratio is a test that measures the amount of proteins called albumin and globulin in your blood. The A/G ratio may be performed as part of a routine blood test called the comprehensive metabolic panel (CMP) or ordered if you have certain unusual symptoms like hematuria (blood in the urine) or jaundice (yellowing of the eyes or skin).

A high A/G ratio may indicate kidney disease, antibody deficiencies, or severe dehydration. A low A/G ratio can also indicate kidney disease as well as liver disease, chronic infections like human immunodeficiency virus (HIV), autoimmune diseases like lupus, and certain cancers.

This article explains why the A/G ratio test is used and what the ratio of albumin to globulin says about your health. It also describes what you need to do if your test results are high or low.

Albumin/Globulin Ratio Results: What's Measured

The A/G ratio describes the amount of albumin compared to the amount of globulin in your blood. Albumin and globulin are major proteins in your blood, called serum proteins. They have different purposes in the human body, as follows:

• Albumin is the most common serum protein made by the liver. It helps fluids remain inside arteries and veins and prevents them from leaking into your lungs, abdomen, or other parts of your body. A normal albumin range is between 3.4 and 5.4 grams per deciliter (g/dL).
• Globulins are a group of serum proteins, some of which are produced by the liver and others by the immune system (immunoglobulins). Globulin plays a central role in liver function, blood clotting, and fighting infections. A normal globulin range is between 2.0 and 3.5 g/dL.

Under normal circumstances, there is slightly more albumin in your blood than globulin.

While the reference ranges of values (meaning the range between which test results are normal) can differ by the lab, most consider an A/G ratio between 1.1 and 2.5 as normal.

What Do High or Low A/G Ratio Results Mean?

When your body is functioning normally, the proportion of albumin to globulin will remain relatively consistent. When the proportion changes and the A/G ratio is either high or low, it may be a sign of an infection, disease, or nutritional deficiency.

Low A/G Ratio

Generally speaking, your A/G ratio may become low for three reasons:

• Your albumin is normal, but your globulin is high.
• Your albumin is low, and your globulin is high.
• Your globulin is normal, but your albumin is low.

High globulin levels are typically a sign of inflammation and the activation of the immune system to fight an infection or disease.

Low albumin levels (referred to as hypoalbuminemia) are most often due to the excessive excretion of albumin through the kidneys or the reduced production of albumin in the liver. Chronic inflammatory conditions can also contribute to hypoalbuminemia by increasing the permeability of blood vessels, allowing albumin to leak into surrounding tissues.

Given these dynamics, the possible causes of a low A/G ratio include:

• Chronic kidney disease
• Liver disease (including cirrhosis)
  
• Pancreatitis (inflammation of the pancreas)
• Chronic infections (such as HIV, tuberculosis, and hepatitis)
• Malnutrition (which decreases the amino acids needed to make albumin)
  
• Autoimmune diseases (such as lupus and rheumatoid arthritis that cause chronic, multi-organ inflammation)
• Gastrointestinal diseases (like celiac disease, ulcerative colitis, and Crohn's disease that cause protein loss)
• Gastrointestinal (GI) cancers (like stomach cancer, colon cancer, and pancreatic cancer)
• Multiple myeloma (a type of blood cancer that blocks the production of albumin and increases globulin levels)
• Type 2 diabetes (in which low insulin decreases albumin production while persistently high blood sugar causes kidney damage)
• Nephrotic syndrome (a complication of kidney diseases that causes too much protein to be excreted from the body in urine)

A low A/G ratio does not cause symptoms per se other than those related to the underlying cause.

In many cases, a person with a low A/G ratio will have no symptoms, particularly those with chronic kidney disease who can be asymptomatic (symptom-free) for years.

Even so, your healthcare provider may order an A/G ratio test if you have signs of chronic kidney disease (including difficulty urinating, ankle swelling, and ammonia-smelling breath) or liver disease (including jaundice, dark urine, severe fatigue, and pain in the upper right abdomen).

High A/G Ratio

A high A/G ratio is far less common than a low A/G ratio and can occur when:

• Your albumin is high, and your globulin is normal.
• Your globulin is low, and your albumin is normal.
• Your albumin and globulin are both high, but the proportion is abnormal.

Globulin levels can drop when your body is not able to produce enough or an excessive amount is eliminated through the kidneys when you urinate.

The only situation in which albumin can abnormally increase is with severe dehydration. In such cases, albumin will increase in relationship to decreased volumes of blood plasma (the liquid part of the blood).

Given these dynamics, possible causes of a high A/G ratio include:

• Severe diarrhea or vomiting (or other causes of severe dehydration)
• Pregnancy (during which albumin and globulin will increase to support fetal growth)
• Antibody deficiency disorders (a group of genetic disorders that cause the inadequate production of immunoglobulins)

As with a low A/G ratio, a high A/G ratio does not cause a set group of symptoms. In many cases, there may be no symptoms at all.

However, people with antibody deficiencies are vulnerable to a host of symptoms, including recurrent infections (especially of the ears, sinuses, and lungs) as well as bacterial or viral meningitis and chronic diarrhea.

Follow-Up for High or Low A/G Test Results

An A/G ratio cannot diagnose any medical condition on its own, but it can point your healthcare provider in the direction of possible causes. Other tests can help characterize the nature of the problem and help narrow the causes.

These involve lab tests like:

• Complete blood count (CBC): A standard panel of blood tests that can detect signs of inflammation or infection
• Urinalysis: A urine-based test that can detect excess protein in urine (proteinuria)
• Creatinine clearance (CrCl): A blood test that can detect a waste product called creatinine that can accumulate in the blood when the kidneys are damaged
• Estimated glomerular filtration rate (eGFR): A test that calculates how well or how poorly the filtering unit of the kidneys, called glomeruli, are working
• C-reactive protein (CRP): A blood test that can detect generalized inflammation in the body
• Erythrocyte sedimentation rate (ESR): A blood test that measures general inflammation based on how quickly red blood cells settle to the bottom of a test column
• Liver function tests (LFTs): A battery of tests used to check for signs of liver disease
• Antinuclear antibody (ANA): A blood test that can check for abnormal antibodies seen with different types of autoimmune diseases

Imaging tests and specialist procedures may be also ordered if a gastrointestinal disease or cancer is suspected. These may include:

• Imaging studies: Including X-ray, ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI)
• Endoscopy: A minimally invasive test in which a fiberoptic scope is inserted into the mouth or rectum to view the digestive tract
• Biopsy: A procedure used to obtain a sample of tissue samples for evaluation in the lab to check for cancer, inflammatory diseases, or certain autoimmune disorders
  

Summary

An A/G ratio is a blood test that compares the amount of two proteins (albumin and globulin) in your blood. A normal A/G ratio is between 1.1 and 2.5, although this can vary by lab.

A low A/G ratio may be due to kidney disease, liver disease, chronic infections, type 2 diabetes, malnutrition, certain autoimmune diseases, and cancers. A high A/G ratio may also be due to kidney disease as well as severe dehydration, pregnancy, and antibody deficiencies.