Diabetic kidney disease is a complication that occurs in some people with diabetes. It can progress to kidney failure in some cases. Treatment aims to prevent or delay the progression of the disease. Also, it aims to reduce the risk of developing cardiovascular diseases such as heart attack and stroke which are much more common than average in people with this disease.
Understanding the kidneys and urine
The two kidneys lie to the sides of the upper part of the tummy (abdomen), behind the intestines and either side of the spine. Each kidney is about the size of a large orange but bean-shaped.
A large artery - the renal artery - takes blood to each kidney. The artery divides into many tiny blood vessels (capillaries) throughout the kidney. In the outer part of the kidneys, tiny blood vessels cluster together to form structures called glomeruli.
Each glomerulus is like a filter. The structure of the glomerulus allows waste products and some water and salt to pass from the blood into a tiny channel called a tubule whilst keeping blood cells and protein in the bloodstream.
Each glomerulus and tubule make up a nephron. There are about one million nephrons in each kidney.
As the waste products and water pass along the tubule there is a complex adjustment of the content. For example, some water and salts may be absorbed back into the bloodstream, depending on the current level of water and salt in your blood. Tiny blood vessels next to each tubule enable this 'fine tuning' of the transfer of water and salts between the tubules and the blood.
The liquid that remains at the end of each tubule is called urine. This drains into larger channels (collecting ducts) which drain into the inner part of the kidney (the renal pelvis). The urine then passes down a tube called a ureter which goes from each kidney to the bladder. Urine is stored in the bladder until it is passed out when we go to the toilet.
The 'cleaned' (filtered) blood from each kidney collects into a large vein - the renal vein - which takes the blood back towards the heart.
What are the main functions of the kidneys?
The main functions of the kidneys are to:
- Filter out waste products from the bloodstream to be passed out in the urine.
- Help control blood pressure - partly by the amount of water passed out of the body as urine and partly by making hormones which are involved in blood pressure control.
- Make a hormone called erythropoietin ('epo') which stimulates the bone marrow to make red blood cells. This is needed to prevent anaemia.
- Help keep various salts and chemicals in the blood at the right level. For example, sodium, potassium, calcium and phosphate. An imbalance of salts and chemicals in the bloodstream can cause problems in other parts of the body.
What is diabetic kidney disease?
Diabetic kidney disease (diabetic nephropathy) is a complication that occurs in some people with diabetes. In this condition 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.
Diabetic kidney disease is divided into two main categories, depending on how much albumin is lost through the kidneys:
- Microalbuminuria: in this condition, the amount of albumin that leaks into the urine is between 30 and 300 mg per day. It is sometimes called incipient nephropathy.
- Proteinuria: in this condition the amount of albumin that leaks into the urine is more than 300 mg per day. It is sometimes called macroalbuminuria or overt nephropathy.
How does diabetic kidney disease develop and progress?
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. These chemicals tend 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.
Microalbuminuria - where the amount of albumin that leaks into the urine is between 30 and 300 mg per day - is usually the first sign that diabetic kidney disease has developed. Over months or years, microalbuminuria may go away (especially if treated - see below), persist at about the same level, or progress to proteinuria.
Proteinuria - where the amount of albumin that leaks into the urine is more than 300 mg per day - is irreversible. If you develop proteinuria it usually marks the beginning of a gradual decline in kidney function towards end-stage kidney failure at some time in the future.
How common is diabetic kidney disease?
Although diabetic kidney disease is more common in people with type 1 diabetes, there are more people with type 2 diabetes and diabetic kidney disease. This is because type 2 diabetes is much more common than type 1 diabetes.
Diabetic kidney disease is actually the most common cause of kidney failure. Around one in five people needing dialysis have diabetic kidney disease.
Note: most people with diabetes do not need dialysis.
For people with type 1 diabetes
Microalbuminuria or proteinuria (defined above) is rarely present at the time when the diabetes is first diagnosed. By five years after the diagnosis of diabetes, about 14 in 100 people will have developed microalbuminuria. After 30 years, about 40 in 100 people will have developed microalbuminuria. Some people with microalbuminuria progress to proteinuria and kidney failure.
For people with type 2 diabetes
At the time the diabetes is first diagnosed, about 12 in 100 people have microalbuminuria and 2 in 100 have proteinuria. This is not because diabetic kidney disease happens straightaway in some cases but because many people with type 2 diabetes do not have their diabetes diagnosed for quite some time after the disease had begun. Of those people who do not have any kidney problem when their diabetes is diagnosed, microalbuminuria develops in about 15 in 100 people and proteinuria in 5 in 100 people, within five years.
Diabetic kidney disease is much more common in Asian and black people with diabetes than in white people.
What are the symptoms of diabetic kidney disease?
You are unlikely to have symptoms with early diabetic kidney disease - for example, if you just have microalbuminuria (defined above). Symptoms tend to develop when the kidney disease progresses. 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.
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 and assessed?
Diabetic kidney disease is diagnosed when the level of albumin in the urine is raised and there is no other obvious cause for this. Urine tests are part of the routine checks that are offered to people with diabetes from time to time. Urine tests can detect albumin (protein) and measure how much is present in the urine.
The standard routine urine test is to compare the amount of albumin with the amount of creatinine in a urine sample. This is called the albumin:creatinine ratio (ACR). Creatinine is a breakdown product of muscle.
A blood test can show how well the kidneys are working. The blood test measures the level of creatinine, which is normally cleared from the blood by the kidneys. If your kidneys are not working properly, the level of creatinine in the blood goes up. An estimate of how well your kidneys are working can be made by taking into account the blood level of creatinine, your age and your sex. This estimate of kidney function is called the estimated glomerular filtration rate (eGFR).
What increases the risk of developing diabetic kidney disease?
All people with diabetes have a risk of developing diabetic kidney disease. However, a large research trial showed that there are certain factors that increase the risk of developing this condition. These are:
- A poor control of your blood sugar (glucose) levels. (The greater your HbA1c level, the greater your risk.)
- The length of time you have had diabetes.
- The more overweight you become.
- Having high blood pressure. The higher your blood pressure, the greater your risk.
- If you are male.
This means that having a good control of your blood glucose level, keeping your weight in check and treating high blood pressure will reduce your risk of developing diabetic kidney disease.
If you have early diabetic kidney disease (microalbuminuria), the risk that the disease will become worse is increased with:
- The poorer the control of blood sugar levels. The greater your HbA1c level, the greater your risk.
- Having high blood pressure. The higher your blood pressure, the greater your risk.
What are the possible complications?
End-stage kidney failure
In people with proteinuria (described above), end-stage kidney failure develops in approximately 8 in 100 people after 10 years. If this occurs then you would need kidney dialysis or a kidney transplant.
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 the proteinuria phase of the disease.
- 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.
An angiotensin-II receptor antagonist (AIIRA)
There are several types and brands of this type of medication. 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.)
Good control of your blood sugar (glucose) level
This 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 at 130/80 mm Hg or more then one or more additional medicines may be advised to lower your blood pressure to below this level.
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
Where relevant, to tackle lifestyle risk factors
- 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 heathy weight.
- Take regular physical activity.
- Cut back if you drink a lot of alcohol.
What is the outlook (prognosis)?
If you have microalbuminuria (described above), this may clear away, especially with treatment.
If you have proteinuria (described above), over time the disease tends to become worse and progress to end-stage kidney failure. However, the length of time this takes can vary and it may take years. If your kidneys do begin to fail you should be referred to a kidney specialist. Once the kidney function goes below a certain level then you will need kidney dialysis or a kidney transplant.
A main concern is the increased risk of developing cardiovascular diseases. Cardiovascular diseases, such as heart attack and stroke, are the main causes of death in people with diabetic kidney disease. The treatments outlined above will reduce the risk of these occurring.
Dr Tim Kenny
Dr Colin Tidy
Dr John Cox