Diabetic kidney disease

What is diabetic kidney disease?

Diabetic kidney disease (diabetic nephropathy) is a complication that occurs in some people with diabetes. Diabetic kidney disease is one of the causes of chronic kidney disease, a long-term condition where the kidneys do not work as well as they should.

In diabetic kidney disease, the filters of the kidneys, the glomeruli, become damaged. Because of this the kidneys 'leak' abnormal amounts of protein from the blood into the urine. The main protein that leaks out from the damaged kidneys is called albumin.

In normal healthy kidneys only a tiny amount of albumin is found in the urine. A raised level of albumin in the urine is the typical first sign that the kidneys have become damaged by diabetes.

If diabetic kidney disease gets worse, the amount of protein leaking into the urine increases, and the kidneys' ability to filter blood reduces. In some people, it can eventually lead to kidney failure.

How does diabetic kidney disease develop?

A raised blood sugar (glucose) level that occurs in people with diabetes can cause a rise in the level of some chemicals within the kidney, which leads to damage. This damage tends to make the glomeruli more 'leaky' which then allows albumin to leak into the urine.

In addition, the raised blood glucose level may cause some proteins in the glomeruli to link together. These 'cross-linked' proteins can trigger a localised scarring process. This scarring process in the glomeruli is called glomerulosclerosis. It usually takes several years for glomerulosclerosis to develop and it only happens in some people with diabetes.

As the condition becomes worse, scarred tissue (glomerulosclerosis) gradually replaces healthy kidney tissue. As a result, the kidneys become less and less able to do their job of filtering the blood. This gradual 'failing' of the kidneys may gradually progress to what is known as end-stage kidney failure.

How common is diabetic kidney disease?

Diabetic kidney disease is common. Around 30 to 40% of people with diabetes (both type 1 diabetes and type 2 diabetes) develop some form of diabetic kidney disease.

Diabetic kidney disease is actually the most common cause of kidney failure in the UK. Around one in five people needing dialysis have diabetic kidney disease, and this will probably increase in future.

Note: most people with diabetes do not need dialysis.

For people with type 1 diabetes

Roughly 1 in 10 people with diabetes have type 1 diabetes.

Type 1 diabetes is an autoimmune condition where the body's immune system destroys the cells that make insulin. It usually begins in childhood or adolescence.

People with type 1 diabetes usually don't have any signs of kidney disease when type 1 diabetes is first diagnosed. Instead, it can develop years later.

By five years after the diagnosis of diabetes, about 1 in 7 people with type 1 diabetes will have signs of early diabetic kidney disease on urine tests.

This increases to about 4 in 10 people after 30 years.

Between 1 in 10, to 3 in 10, people with type 1 diabetes develop kidney failure needing dialysis in their lifetime.

For people with type 2 diabetes

About 9 in 10 people with diabetes have type 2 diabetes.

Type 2 diabetes is when the body becomes resistant to the effects of insulin, or doesn't produce enough insulin. It has lots of different causes, including a link to overweight and obesity.

It's more common for people with type 2 diabetes to have signs of diabetic kidney disease when the diabetes is first diagnosed. About 1 in 8 people have early signs of diabetic kidney disease on urine tests, when the diabetes is first diagnosed.

This is probably because they have already had type 2 diabetes for some time before being diagnosed.

Up to 4 in 10 people with type 2 diabetes develop some form of diabetic kidney disease eventually. Amongst people without any kidney disease when diagnosed with type 2 diabetes, this usually takes 5-10 years, or longer, to develop.

Some people with type 2 diabetes develop kidney failure needing dialysis. It's difficult to give a precise figure of how likely this is, mainly because it differs a lot, depending on how long someone lives with type 2 diabetes for.

People who are diagnosed with type 2 diabetes at a young age are more likely to develop kidney failure needing dialysis. One study estimates that around 1 in 10 people diagnosed with type 2 diabetes before the age of 40 will eventually develop kidney disease needing dialysis.

Diabetic kidney disease is much more common in South Asian and Black people with diabetes than in white people. We don't fully understand why this is.

Diabetic kidney disease symptoms

Kidney disease usually doesn't cause any symptoms until it reaches an advanced stage.

This is why it's important for people with diabetes to have regular testing (see "How is diabetic kidney disease diagnosed?", below) to detect and treat diabetic kidney disease early.

When kidney disease does cause symptoms, the symptoms at first tend to be vague and nonspecific, such as feeling tired, having less energy than usual and just not feeling well. With more severe kidney disease, symptoms that may develop include:

• Difficulty thinking clearly.

• A poor appetite.

• Weight loss.

• Dry, itchy skin.

• Muscle cramps.

• Fluid retention which causes swollen feet and ankles.

• Puffiness around the eyes.

• Needing to pass urine more often than usual.

• Being pale due to anaemia.

• Feeling sick (nausea).

As the kidney function declines, various other problems may develop - for example, anaemia and an imbalance of calcium, phosphate and other chemicals in the bloodstream. These can cause various symptoms, such as tiredness due to anaemia, and bone 'thinning' or fractures due to calcium and phosphate imbalance. End-stage kidney failure is eventually fatal unless treated.

How is diabetic kidney disease diagnosed?

Diabetic kidney disease is diagnosed when urine and blood tests show signs of kidney disease, and there is no other explanation aside from the diabetes.

These are:

• A urine test for protein, usually one called the albumin:creatinine ratio (ACR). A raised ACR means there is an increased level of protein in the urine. This is usually one of the first signs of diabetic kidney disease.

  • An ACR level of less than 3mg/mmol is normal.

  • An ACR level between 3mg/mmol and 30mg/mmol is moderately raised. This is called microalbuminuria and usually indicates early diabetic kidney disease.

  • An ACR level above 30mg/mmol is significantly raised. This is called albuminuria or proteinuria and indicates more advanced diabetic kidney disease.

• A blood test to measure how well the kidneys are filtering the blood. This is usually a test for a chemical called creatinine, to calculate an estimated glomerular filtration rate, or eGFR, which measures how well the kidneys are working.

  • An eGFR of 60 or higher is normal, unless there are other signs of kidney disease (such as protein in the urine).

  • An eGFR between 15 and 59 indicates reduced kidney function.

  • An eGFR below 15 indicates kidney failure.

In diabetic kidney disease, the urine tests (ACR) can be raised with a normal blood test (eGFR), particularly in the early stages. Some people also have a reduced eGFR with a normal urine ACR.

This is why it's important to check both urine and blood tests.

People with diabetes should have blood and urine tests checked once a year, as part of routine monitoring. Some people may need to have tests done more often.

Urine and blood kidney tests can be affected by any cause of kidney disease. So, if it's not clear whether a kidney problem is due to diabetes or something else, other tests may be recommended to look for other causes, such as blood tests or an ultrasound.

Rarely, if the diagnosis is still unclear, a kidney specialist may recommend a kidney biopsy. This can help to determine if reduced kidney function is due to diabetic kidney disease, or something else.

What increases the risk of developing diabetic kidney disease?

Diabetic kidney disease can affect anyone with diabetes.

There are some things that are known to increase the risk of getting diabetic kidney disease:

• A poor control of your blood sugar (glucose) levels. (The greater your HbA1c level, the greater your risk.)

• Having diabetes for a longer time.

• Having overweight or obesity.

• Having high blood pressure. The higher your blood pressure, the greater your risk.

• Smoking.

• Being male.

• Being of South Asian or Afro-Caribbean ancestry.

This means that having a good control of your blood glucose level, keeping your weight at a healthy level, and treating high blood pressure will reduce your risk of developing diabetic kidney disease. Stopping smoking is also important, if you smoke.

What are the possible complications?

End-stage kidney failure

Diabetic kidney disease can sometimes lead to kidney failure, or end-stage kidney disease.

End-stage kidney disease is when the kidneys are no longer able to function well enough to keep someone alive. The only treatments are dialysis or a kidney transplant.

Diabetic kidney disease is the leading cause of end-stage kidney disease in the UK.

The risk of developing end-stage kidney disease differs from person to person. Having high levels of protein in the urine (proteinuria) increases this risk.

Getting good diabetic control, keeping blood pressure under control, maintaining a healthy weight, and (if needed) using medications to treat diabetic kidney disease all reduce the risk of developing end-stage kidney disease.

Cardiovascular diseases

All people with diabetes have an increased risk of developing cardiovascular diseases, such as heart disease, stroke and peripheral arterial disease. If you have diabetes and diabetic kidney disease, your risk of developing cardiovascular diseases is increased further.

The worse the kidney disease, the further increased the risk. This is why reducing any other cardiovascular risk factors is so important if you have diabetic kidney disease (see below).

High blood pressure

Kidney disease has a tendency to increase blood pressure. In addition, increased blood pressure has a tendency to make kidney disease worse. Treatment of high blood pressure is one of the main treatments of diabetic kidney disease.

What is the treatment for diabetic kidney disease?

Treatments that may be advised are discussed below. Treatments aim to:

• Prevent or delay the disease progressing to kidney failure. In particular, if you have early diabetic kidney disease (microalbuminuria) it does not always progress to more severe kidney disease - which is why it's important to try to detect and treat microalbuminuria early.

• Reduce the risk of developing cardiovascular diseases such as heart disease and stroke.

An angiotensin-converting enzyme (ACE) inhibitor

There are several types and brands of this type of medication. ACE inhibitors work by reducing the amount of a chemical called angiotensin II that you make in your bloodstream. This chemical tends to narrow (constrict) blood vessels.

Therefore, less of this chemical causes the blood vessels to relax and widen and so the pressure of blood within the blood vessels is reduced.

ACE inhibitors are medicines that are often used to treat high blood pressure. However, the way they work also seems to have a protective effect on the kidneys and heart. This means that they help to prevent or delay the progression of the kidney disease.

It's therefore worth using them in people with diabetic kidney disease even if their blood pressure is normal.

An angiotensin-II receptor antagonist (AIIRA)

There are several types and brands of this type of medication. The ones available in the UK are: azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan and valsartan. AIIRAs work in a similar way to ACE inhibitors.

One may be used instead of an ACE inhibitor if you have problems or side-effects with taking an ACE inhibitor. (For example, some people taking an ACE inhibitor develop a persistent cough.)

SGLT2 inhibitors

Examples of these medications include dapagliflozin and empagliflozin.

SGLT2 inhibitors work by causing glucose (sugar) to pass into the urine, lowering blood sugar levels. They are commonly used to treat type 2 diabetes.

They also reduce pressure in the kidneys, which helps to prevent or slow kidney disease. They are also useful for treating heart failure, and can help to protect against further heart disease in people with atherosclerosis.

SGLT2 inhibitors are particularly useful in people with type 2 diabetes and diabetic kidney disease who still have high levels of protein in their urine, despite taking an ACE inhibitor or angiotensin-II receptor antagonists.

Because of the increasing evidence of benefit in many different areas, SGLT2 inhibitors are increasingly being used in people with type 2 diabetes now, even if they do not have diabetic kidney disease.

SGLT2 inhibitors have been used to treat diabetic kidney disease in people with type 1 diabetes, but this is a new area under research. So far, research suggests that they are helpful at treating diabetic kidney disease in type 1 diabetes, but increase the risk of developing diabetic ketoacidosis. They should only be used in type 1 diabetes under the direction of a diabetes specialist.

Finerenone

Finerenone is a new drug which blocks the action of certain hormones (mineralocorticoids) which may damage the kidneys.

In the UK, it's currently recommended as an option for people with type 2 diabetes who have stage 3 or 4 kidney disease and albuminuria, if they are already on the maximum dose of an ACE inhibitor or angiotensin-II receptor antagonist and an SGLT2 inhibitor.

Currently, it's usually started by kidney specialists.

Good control of your blood glucose level

Good control of your blood sugar (glucose) level will help to delay the progression of the kidney disease and to reduce your risk of developing associated cardiovascular diseases, such as heart disease and stroke.

Ideally, the aim is to maintain your HbA1c to less than 48 mmol/mol but this may not always be possible to achieve and the target level of HbA1c should be agreed on an individual basis between you and your doctor.

Good control of your blood pressure

Strict blood pressure control is likely to reduce the risk of developing cardiovascular diseases and prevent or delay the progression of kidney disease. Most people should already be taking an ACE inhibitor or AIIRA (described above). These medicines lower blood pressure.

However, if your blood pressure remains high, then one or more additional medicines may be advised to lower your blood pressure.

Review of your medication

Certain medicines can affect the kidneys as a side-effect which can make diabetic kidney disease worse. For example, you should not take anti-inflammatory medicines unless advised to by a doctor. You may also need to adjust the dose of certain medicines that you may take if your kidney disease becomes worse.

Other treatments to reduce risk factors

A medicine to lower your cholesterol level (such as a statin) is commonly advised. This will help to lower the risk of developing some complications such as heart disease, peripheral arterial disease and stroke.

Where relevant, to tackle lifestyle risk factors, which include:

• Stop smoking if you smoke.

• Eat a healthy diet. However, those with established kidney damage may need to reduce the protein in their diet and limit sodium, potassium and phosphorus intake.

• Keep your weight and waist in check. Those with established disease may need to increase calories, if they develop problems maintaining a healthy weight.

• Take regular physical activity.

• Cut back if you drink a lot of alcohol.

What is the outlook?

The outlook for diabetic kidney disease can vary a lot depending on many different factors.

Diabetic kidney disease can get worse over time. If so, it usually gets slowly worse over years. But treatment for diabetic kidney disease can slow or sometimes stop this from happening.

In people with microalbuminuria (mild-to-moderate increases in albumin in the urine), treatment often reduces the albumin level back to normal.

People with proteinuria (significantly raised levels of albumin in the urine) are more likely to go on to develop end-stage kidney disease, but, again, treatment can slow or sometimes stop this happening.

Most people with diabetic kidney disease never get to the stage of needing dialysis or a kidney transplant, but some people do.

People with diabetic kidney disease are more likely to get cardiovascular diseases, such as heart attacks or strokes. It's important to make lifestyle changes and consider treatments (detailed above) to reduce the chances of this happening.