Blood Test – ALP & its Significance in CKD

ALP is one of those blood tests people don’t pay a huge amount of attention to and often don’t understand what it is measuring. It is often just looked at as a marker of liver function, but it can provide a lot more information about your health than that and for people with CKD it is something that should be monitored and if elevated, acted upon. 

Let’s take a look at what ALP is, what may cause high (and low) levels of ALP, and why this marker is particularly important for people with CKD.  

What is ALP?

Alkaline phosphatase (ALP) is an enzyme found in all tissues in the human body. An enzyme is a type of protein that catalyzes (causes or accelerates) chemical reactions in the body. ALP is produced mainly by the liver and bones but is also synthesized in smaller amounts by the intestines and kidneys. ALP is also secreted from the placenta during pregnancy.

Scientists have not yet identified the full range of biochemical reactions that ALP instigates, but the enzyme is known to contribute to the following processes:

• Transporting nutrients and enzymes to and from the liver
• Aiding in the development, growth, and maintenance of bone
• Transporting calcium and phosphate from the intestines to bones, muscles, and nerve cells to ensure normal function
• Transporting fatty acids to store energy in adipose tissues and help maintain the structural integrity of cells
• Regulating cell growth in fetuses during pregnancy

Testing ALP

The level of ALP in the blood is checked through a blood test and is often measured as part of a liver function panel along with some other enzymes.

The normal levels of ALP differ depending on factors such as age and sex. Blood levels of ALP also increase by two to four times during pregnancy- this is a result of additional ALP produced by the placenta. Reference ranges will vary slightly between pathology labs. 

https://www.rcpa.edu.au/Manuals/RCPA-Manual/General-Information/IG/Table-6-Reference-intervals-harmonised-chemical

Causes of elevated ALP

There are a number of different things that can cause someone’s ALP to be raised on a blood test and ALP should be assessed alongside other blood tests and symptoms to help determine why the level is elevated. Generally speaking, elevated ALP will come from either a liver or bone origin.

Some potential causes of elevated ALP include: 

Liver Indications:

• Impaired bile flow (Fatty liver, Cirrhosis, Gall stones)
• Biliary obstruction
• Hepatitis
• Cirrhosis
• Congestive heart failure
• Drug-induced liver toxicity
• Liver cancer and Bile duct cancer
• Impaired liver detoxification

Non-Liver Indications:

• Bone loss, turnover, or repair
• Healing bone fractures
• Paget’s Bone disease
• Osteoporosis
• Malignancy
• Hyperparathyroidism
• Rickets/Osteomalacia
• Chronic kidney disease
• Thyrotoxicosis
• Rheumatoid Arthritis
• Intestinal disease (eg. Inflammatory Bowel Disease, Coeliac disease)
• Pregnancy
• Certain medications

https://www.bmj.com/content/346/bmj.f976.full

Generally speaking, if ALP is elevated alongside other liver enzymes (eg. ALT, AST, and GGT) then it is more likely to be coming from one of the liver indications but if ALP is elevated without elevations in other liver enzymes, then it is more likely to be due to non-liver indications.

Causes of low ALP

Having elevated ALP is certainly more common but some people may have low levels of ALP. Some causes of low ALP include:

• Hypophosphatasia
• Malnutrition
• Magnesium deficiency
• Vitamin B6 deficiency
• Zinc deficiency 
• Hypothyroidism
• Severe anemia 
• Wilson’s disease

Significance of ALP in people with CKD

So what does it mean if ALP is elevated in someone with CKD?

Well, obviously there are a number of different causes of elevated ALP which may also be present in someone with kidney disease. The first thing to look at would be the results of other blood tests and specifically other liver enzymes such as ALT, AST, and GGT. As I mentioned earlier, if these are elevated then it is possible that the elevated ALP is coming from a liver source.

However, if ALP is elevated on its own, it may indicate a high turnover of bone or CKD-mineral and bone disorder (CKD-MBD). 

CKD causes mineral and bone disorder because the kidneys don’t properly balance the mineral levels in the body resulting in alterations in levels of calcium, phosphorus, parathyroid hormone, and vitamin D. Metabolic acidosis which is commonly found in people with CKD also contributes to increased bone turnover and CKD-MBD because when the body is too acidic, alkalizing minerals like calcium and magnesium are pulled out of bone to try and alkalize the body. 

High bone turnover and CKD-MBD cause bones to become thin and weak, increasing the risk of fractures and can also cause problems in the heart and blood vessels.

Problems associated with high levels of ALP

When ALP is elevated in people with CKD it may indicate the following:

1. Increased bone turnover or CKD-MBD can lead to weak bones and an increased risk of fractures.

2. Vascular calcification 

Vascular calcification is a process that leads to the accumulation of calcium phosphate crystals in blood vessel walls causing thickening and loss of elasticity in blood vessel walls. This contributes to increased blood pressure, atherosclerosis (hardening of the arteries), increases the risk of heart attack, stroke, and dementia and can result in inadequate blood supply to the legs and throughout the body.

Vascular calcification is one of the strongest predictors of cardiovascular risk and is associated with significant morbidity and mortality. In people with CKD, it increases the risk of cardiovascular events and mortality contributes to further kidney damage, and is associated with an increased risk of kidney disease progression. 

3. Inflammation

Higher ALP levels have also been associated with increased inflammation in people with and without CKD.  Multiple studies have shown that people with higher ALP levels also have elevated CRP (C-reactive protein) levels. CRP is a protein made by the liver that increases when there is inflammation in the body. 

Persistent, low-grade inflammation has been recognized as an important component of the CKD scenario, leading to fibrosis (scarring) and loss of renal function, and plays a crucial role in both the development and progression of kidney disease and is also linked to the presence of other complications like proteinuria, osteoporosis, protein-energy wasting, and cardiovascular disease. 

 4. Increased risk of cardiovascular events

Elevated ALP levels have been associated with increased risk of cardiovascular events, hospitalization, and mortality in the general population and in people with CKD. This is likely to be due to a combination of vascular calcification, arterial stiffness, and increased inflammation. 

What to do if ALP levels are elevated

So, what should you do if your ALP levels are elevated on your blood test?

Firstly, the most important step is to try to determine the CAUSE because treatment varies depending on what the underlying cause is. Addressing high ALP due to a liver issue is very different from addressing high ALP due to increased bone turnover!

This may require further testing to assist your doctor or healthcare provider to determine what is going on. 

Specific blood tests that should be done if CKD-MBD is suspected are phosphate, calcium, parathyroid hormone, and vitamin D. 

Some other helpful tips include:

• Reduce intake of foods high in phosphorus- high levels of phosphorus cause calcium to be pulled out of the bones, contributing to the development of CKD-MBD and can lead to calcium deposits in blood vessels, lungs, eyes, and the heart. 

• Ensure adequate vitamin D levels- vitamin D deficiency can cause elevated ALP.

• Follow an alkaline diet- when the body is acidic minerals like calcium and magnesium can be pulled out of bones to try to bring the body into a more alkaline state. This further weakens bones and can contribute to vascular calcification.

• Use alkalizing supplements if necessary to treat metabolic acidosis.

• Improve kidney function- anything you do to help heal your kidneys and improve your kidney function will have the added benefit of reducing bone turnover, improving CKD-MBD, lowering inflammation and reducing cardiovascular risk.

• Work on lowering inflammation- this includes eating an anti-inflammatory diet, exercising, getting enough sleep, managing stress, and looking after your gut health.

• Maintain a healthy weight- this will help to lower inflammation and reduce cardiovascular risk.

• Weight-bearing exercise- has been shown to decrease bone ALP activity and help to slow bone loss and even build bone. If you have CKD-MBD or osteoporosis, then make sure you discuss an appropriate exercise regime with a healthcare practitioner first.

• Vitamin K2- vitamin K2 may help reduce vascular calcification and arterial stiffness by redirecting calcium from soft tissues and arteries back to your bones.

• Omega-3 fatty acids- can help to prevent/reduce vascular calcification, lower inflammation, reduce cardiovascular risk, and improve bone quality.

Make sure you discuss any new supplements with your healthcare provider first to ensure they are appropriate for your use. 

Final Words

I really encourage everyone to get copies of their blood tests and ask their doctor or healthcare practitioner what their results mean. Too often, people aren’t informed about what their blood tests are showing until there is something severely wrong and we all know that prevention is better than cure, and catching problems early means that we are better able to do something about it. 

Hopefully, this article has given you a better understanding of what ALP is measuring and what elevated levels may indicate as well as a starting point to help reduce ALP levels and minimize the potential consequences that may be associated with high levels. 

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