Basics of Diabetic Nephropathy

Saima Andrabi   by Saima Andrabi, MS, Clinical Biochemistry    Last updated on December 12, 2019,

diabetic nephropathy overview

 

What is Diabetic Nephropathy?

Diabetic nephropathy is a serious kidney-related complication of diabetes, and is also called as diabetic kidney disease also. Almost 40 % of people with diabetes ultimately develop kidney disease. Diabetic nephropathy interferes with the ability of kidneys to do their usual work of removing waste products and extra fluids from the body. Over many years, the condition slowly damages the kidney’s delicate filtering system. However, an early treatment may help in preventing or slowing the disease progression and thereby reducing the chances of further complications.

Kidney diseases if not treated may progress to kidney failure or end-stage kidney disease. In diabetic nephropathy or diabetic kidney disease, the kidneys are damaged because of diabetes and the high blood glucose levels in diabetes damage the part of the kidneys that filters the blood. As a result, the damaged filter becomes leaky and releases the proteins into urine. In some people, diabetic nephropathy can progress to end-stage kidney disease. However, in most people with diabetes, the kidney diseases do not progress to kidney failure or end-stage kidney disease.

Diabetic nephropathy or diabetic kidney disease results from diabetes and is the number one cause of kidney failure. Almost a third of people suffering from diabetes develop diabetic nephropathy. It has been found that people with diabetic kidney diseases have more complications as compared to people with kidney disease alone. This is because people with diabetes have some other medical conditions also like high blood pressure, high cholesterol, and blood vessel diseases like atherosclerosis. Besides, people with diabetes are more prone to have other kidney-related problems like bladder infections and nerve damage to the bladder.

Kidney diseases in type 1 diabetes and type 2 diabetes are slightly different. In type 1 diabetes, kidney disease rarely start developing in the first 10 years after diagnosis of diabetes while in type 2 diabetes, some patients already have kidney disease when they are diagnosed with diabetes.

Signs and Symptoms of Diabetic Nephropathy

The kidneys work hard to make up for the failing capillaries so that kidney disease produces no symptoms until almost all function is lost. Also, the symptoms of kidney disease are unspecific. The first symptom of kidney disease is fluid retention. Other symptoms include improper sleep, less appetite, upset stomach, weakness, and difficulty concentrating.

In the early stages of diabetic nephropathy, most people have no symptoms. Over the years, as kidney disease progresses, small amounts of the blood protein albumin begin to appear in the urine. This is the first stage of chronic kidney disease and is called moderately increased albuminuria or microalbuminuria. At this stage, the kidneys can still filter waste. With further progression in the disease, more albumin protein starts leaking into the urine. This stage is called as severely increased albuminuria or macroalbuminuria. As the albumin levels increase in the blood, kidneys are unable to filter the blood, due to which wastes get accumulated in the blood, resulting in many complications like high blood pressure.

Diabetic nephropathy is not typically characterized by symptom onset, meaning that most individuals who have the disease are unaware of the condition until it has already caused a significant damage. Screening diabetic patients for kidney damage therefore plays an important role in reducing the risk of long-term kidney damage and the associated problems.

In early stages of diabetic nephropathy, there are no symptoms. It takes many years for the kidney disease to progress and the symptoms only appear when the kidney damage has occurred drastically. In severe cases of kidney damage, following symptoms may be found:

  • Weight loss
  • Poor appetite
  • Sick feeling
  • Swelling in the ankles and feet due to fluid retention
  • Puffy eyes
  • Hiccups
  • Dry and itchy skin
  • Cramps in the muscles
  • Frequent urination
  • Feeling tired
  • Difficulty in concentrating
  • Metallic taste in the mouth
  • Nausea
  • Vomiting
  • Appetite loss
  • Protein aversion (lacking interest in eating meat)
  • Swelling in the face or hands
  • Breathlessness
  • Foamy and bubbly urine due to leaking of proteins in urine
  • Blood in the urine
  • Severe anemia
  • Feeling cold all the time
  • Mental confusion
  • Strange desire to chew ice, clay or laundry starch, a condition called pica
  • Abnormal heart rhythms due to increase in potassium levels in the blood
  • Muscle twitching
  • Inability to control blood pressure
  • Lethargy
  • Less need for insulin or diabetes medicine

What are the Causes of Diabetic Nephropathy?

The kidneys consist of many tiny blood vessels that help in filtering waste from the blood. High blood glucose levels in diabetes can destroy these blood vessels. As a result, the kidneys become unable to perform their function and may even stop working completely. This is called kidney failure. It has been found that because of certain conditions like high blood pressure, high cholesterol, smoking etc, diabetic patients are more likely to get diabetic nephropathy.


Hypertension or high blood pressure is a serious complication of diabetes and is believed to contribute most directly to diabetic nephropathy. Hypertension is both a cause of diabetic nephropathy as well as a result of the damage caused by the disease. With the progression of the disease, some physical changes in the kidneys often result in increased blood pressure. If not controlled, hypertension can progress the kidney disease towards stage 5 diabetic nephropathy very rapidly which can be very dangerous.

The high blood sugar associated with diabetes damages the kidneys through many different and complicated pathways. Most of this damage is directed towards the blood vessels that filter the blood and help in making urine. The damaged blood vessels as a result puts stress on kidneys and prevent them from working properly. As a result, following complications may occur:

  • the body’s proteins are lost through the urine
  • the kidneys become unable for removing waste products from the blood
  • the kidneys are not able to maintain healthy fluid levels in the body

Diabetic nephropathy develops very slowly. According to a study, a third of people show elevated levels of albumin in their urine after 15 years of diagnosis of diabetes. Some statistics have suggested that kidney diseases are uncommon in people who have had diabetes for less than 10 years. Also, if people have no clinical signs of nephropathy for 20–25 years after diabetes starts, they are at a lower risk of developing it thereafter.

How Common is Diabetic Nephropathy?

Diabetic nephropathy is very common. Almost one in 4 women and one in 5 men with type 2 diabetes develop diabetic nephropathy. Diabetic nephropathy is even more common in type 1 diabetes. Diabetic kidney disease has been found to be the leading cause of kidney failure in Australia.

How Does Diabetes Cause Kidney Disease?

Protein digestion in our body results in formation of waste products. These waste products are filtered with the help of millions of tiny blood vessels (capillaries) and even tinier holes present in the kidneys, which act as filters. As blood flows through these filters, small molecules such as waste products easily pass through the holes and then become part of the urine. On the other hand, some useful substances like proteins and red blood cells are too big to pass through the holes in the filter and therefore remain in the blood. Diabetes damages this filtering system of the kidneys and high levels of blood glucose make the kidneys to filter large amount of blood. Due to this extra work, the filters become overloaded and hence after many years, they start leaking useful proteins in the urine. If small amounts of protein are leaked in the urine, it is called as microalbuminuria. Microalbuminuria occurs in the early stages of kidney disease and proper treatment at this stage can prevent the disease from getting worse. Presence of larger amounts of protein in the urine is called macroalbuminuria, which is an indication of end-stage renal disease or ESRD. When kidneys lose their filtering ability, waste products start building up in the blood and finally the kidneys fail, called as kidney failure or ESRD. Kidney failure or ESRD is very serious. The treatment options in ESRD is either dialysis or kidney transplant.

Risk factors for Diabetic Nephropathy

There are many factors that can increase the risk of having diabetic nephropathy. Some of the common risk factors include:

  • Family history of kidney disease
  • High blood glucose levels due to poor management of diabetes
  • High blood pressure
  • Overweight or obesity
  • Smoking
  • Age (kidney disease and low GFR is more common in elder people above the age of 65 years)
  • Sex (the condition is more common in men than in women)
  • Race and ethnicity (more common in African Americans, Native Americans, and Asian Americans)
  • Chronic inflammation
  • Insulin resistance
  • Hyperlipidemia

Stages of Diabetic Nephropathy

There are various stages of kidney disease depending on the GFR, which in turn represents the percentage of effective kidney function.

Stage 1

At this stage, some kidney damage is present but there is a normal kidney function and a GFR of 90% or above.

Stage 2

At this stage, the kidney damage is associated with some loss of function and the GFR is 60–89%.

Stage 3

At this stage, there is mild to severe loss of function and a GFR of 30–59%.

Stage 4

At this stage, there is severe loss of function and a GFR of 15–29%.

Stage 5

At this stage, there occurs complete kidney failure and a GFR of fewer than 15%.

How is Diabetic Nephropathy Diagnosed?

In case of diabetic people, yearly blood and urine tests are recommended by doctors to check for early signs of kidney damage. This is because diabetes is a major risk factor for kidney damage. Common diagnostic tests include:

Microalbuminuria Urine Test

This test is used to check the presence of albumin in the urine which is absent in normal urine, so the presence of the protein in the urine is a sign of kidney damage.

BUN Blood Test

This test is used to check the presence of urea nitrogen in the blood. Urea nitrogen is formed in the body due to protein broken down. Higher than normal levels of urea nitrogen in the blood may be a sign of kidney failure.

Serum Creatinine Blood Test

This test measures the creatinine levels in the blood. Normally kidneys remove creatinine from the body by sending it to the bladder, from where it is released with urine. If the kidneys are damaged, they cannot remove the creatinine properly from the blood. Therefore, high creatinine levels in the blood means that the kidneys are not functioning properly.

Kidney Biopsy

If doctors suspect diabetic nephropathy in a patient, they may recommend a kidney biopsy test, which is a surgical procedure for removing a small tissue sample of one or both the kidneys that can be viewed under a microscope.

Screening for Diabetic Nephropathy

In case of adults with type 1 diabetes, screening test should be done after five years from the onset of diabetes and then annually thereafter. For people with type 2 diabetes, a screening test should be done immediately after the diabetes is diagnosed and then annually thereafter. Screening tests are very important for checking the possibility of diabetic nephropathy.

Treatment of Diabetic Nephropathy

Early treatments can usually delay or prevent the onset of diabetic nephropathy. The main aim of treatment should be to maintain and control blood glucose levels and blood pressure. Following treatments are commonly used:

Drug Treatment

Drugs like angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) can be helpful in lowering the blood pressure, protecting kidney function, and preventing any further damage. Besides this, vitamin D supplements are given to people with kidney disease because they often have low vitamin D levels. Statin may be also given to reduce cholesterol levels.

Dietary Changes

A person with kidney disease should keep a track of the following nutrients:

Water: Too much water or fluid should be avoided as it may increase the risk of swelling and high blood pressure due to fluid retention.

Sodium: This mineral can raise blood pressure as it is a constituent of salts.

Protein: In case of persons with kidney disease, protein can cause build up of waste in the blood, which in turn puts extra pressure on the kidneys.

Phosphorus: Avoid too much phosphorus rich foods because it can weaken the bones and put pressure on the kidneys.

Potassium: People with kidney disease have higher levels of potassium than normal, which can affect nerve cells.

Managing blood sugar levels

This is important for lowering the risk of diabetes complications, such as kidney disease, cardiovascular disease, and diabetic neuropathy. All these conditions can lead to further complications. Managing the blood sugar levels can also help in preventing these diseases.

Late-stage treatment options

If diabetic nephropathy progresses to ESRD, a person needs dialysis for the rest of life or until a kidney transplant.

Prevention of Diabetic Nephropathy

To reduce the risk of developing diabetic nephropathy, following steps should be taken:

  • Treat your diabetes so that you can prevent or delay diabetic kidney disease.
  • Avoid high blood pressure or other medical conditions as they increase the risk of kidney disease.
  • Avoid pain killers as they can lead to kidney damage.
  • Maintain a healthy weight by increasing daily physical activity and reducing calories.
  • Avoid smoking as it can damage the kidneys or make any existing kidney damage worse.

What is the Outlook for Diabetic Nephropathy?

Disease progression is based on many factors, however following a treatment plan and making recommended lifestyle changes can decrease the disease’s progression and keep the kidneys healthy for a longer time.

Risk Reduction Strategies for Diabetic Nephropathy

People with diabetes can either reduce their risk of diabetic nephropathy, or delay its onset in following ways:

  • Controlling blood sugar levels
  • Preventing the use of non-steroidal anti-inflammatory drugs (NSAIDS)
  • Treating urinary tract infections quickly with antibiotics
  • Drinking plenty of water
  • Avoiding  x-rays as they can stress the kidneys
  • Maintaining good health of kidneys by performing regular check ups