Diabetic nephropathy is the medical term for kidney disease caused by diabetes. It is the most common cause of kidney failure in the United States, accounting for 40 percent of new cases each year, according to the American Diabetes Association. Nephropathy is a slow deterioration of the kidneys, which can impair kidney function and ultimately lead to failure.

The role of the kidneys is to filter out the body’s waste products, water and other chemicals from the blood. As the kidneys become diseased, the filtration system begins to function improperly. As a result, proteins are released into the urine.

All people with diabetes are susceptible to kidney disease, but those who have type 1 diabetes or who develop type 2 diabetes at an early age are at particular risk. Recent research indicates that nephropathy can even affect people with prediabetes.

Nephropathy can be prevented by controlling glucose (blood sugar) and blood pressure, not smoking, and keeping weight and cholesterol at healthy levels.

Nephropathy can eventually lead to end-stage renal disease (ESRD), when the kidneys are unable to function. At this point, dialysis or kidney transplant are necessary for survival. However, a special urine test can detect diabetic nephropathy early and show the need for treatments such as diet and medication that may prevent or delay further damage.

Recent government statistics show progress against diabetic nephropathy and kidney failure, and scientists are working on new treatments.

Diabetic nephropathy is a type of kidney disease in which the kidneys can no longer function efficiently. Diabetes affects the kidneys by causing the blood vessels to become blocked and leaky. When the kidneys function properly, they filter out waste products from the blood.

The kidneys are bean-shaped structures located in the middle of the back on both sides of the spine. Although small, the kidneys receive about 20 percent of the blood pumped by the heart. In addition to removing waste, the kidneys:

• Maintain the water volume of the body
• Regulate blood pressure
• Maintain calcium level within the body

Each kidney is about the size of a fist and is composed of roughly 1 million filtering units called nephrons. The nephrons themselves are made up of blood vessels called glomeruli.

The glomeruli filter out molecules of waste products and water through constant, stable pressure but do not filter out red blood cells. The waste products form urine, which moves to the bladder to be eliminated while blood returns to the body.

When the nephrons become damaged, the glomeruli can leak protein into the urine, including a type of protein called albumin. This protein helps fluid remain in the bloodstream instead of leaking into the tissues. Diabetic nephropathy can cause the kidneys to lose large amounts of albumin, leading to a condition called microalbuminuria. As a result, the body retains a large amount of waste products and loses important nutrients.

A microalbuminuria test, a special type of urine test, can detect kidney damage early. If microalbuminuria is not found and treated, the result is further kidney damage and the loss of larger amounts of protein in the urine (proteinuria). Another useful tool for detecting and monitoring kidney damage is a calculation called glomerular filtration rate.

About 10 to 20 percent of people with diabetes have nephropathy, and about 40 percent of those with type 2 diabetes will eventually develop it, according to the American Diabetes Association (ADA). Severe nephropathy is more common with type 1 diabetes. Twenty to 40 percent of people with type 1 diabetes experience kidney failure by age 50, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Patients with nephropathy often have the eye disease known as diabetic retinopathy as well. Both conditions are forms of diabetic angiopathy (blood vessel disease). In addition, proteinuria, a hallmark of diabetic nephropathy, has also been linked to heart disease in people with type 2 diabetes.

The ADA estimates that, compared to whites, nephropathy is 2.6 to 5.6 times more common in non-Hispanic blacks, 4.5 to 6.6 times more common in Mexican Americans and 6 times more common in American Indians.

Recent research reveals that people with prediabetes can develop diabetic complications including nephropathy, retinopathy, neuropathy (nerve disease) and heart conditions. In a seven-year project, scientists from the National Institutes of Health (NIH) and elsewhere found that people with prediabetes developed more chronic kidney disease than those with normal glucose (blood sugar) but less than those with diabetes.

End-stage renal disease (ESRD) is the point when the kidneys stop working. Dialysis or a kidney transplant is necessary for survival. About 44 percent of new cases of ESRD are due to diabetes, according to the NIDDK. However, nephropathy can be delayed or even prevented through glucose control, careful monitoring and treatment.

Several recent studies offer promising developments in diabetic nephropathy:

• Despite the increasing incidence of diabetes, the rate of kidney failure in diabetic Americans has dropped 30 percent since its peak in 1996, the Centers for Disease Control and Prevention (CDC) reported in 2005. The CDC also estimated that hospitalization rates for diabetic complications such as kidney failure declined 35 percent between 1994 and 2002.
  
  
• U.S. rates of kidney failure have stabilized since 1999 after a two-decade surge in which rates increased 5 to 10 percent a year, the NIDDK reported.
  
  
• The incidence of ESRD in people with type 1 diabetes appears to have fallen. In a decades-long nationwide study in Finland of 20,000 young people with type 1 diabetes, 2.2 percent of the patients had ESRD 20 years after diagnosis and 7.8 percent after 30 years. This rate is markedly lower than (older) U.S. estimates by the NIDDK. The investigators attributed the improvement to advances in treatment.
  
  
• The long-term Pittsburgh Epidemiology of Diabetes Complications Study (EDC) in 2006 also found declining rates of kidney failure in people with type 1 diabetes. Eighteen percent of those diagnosed with diabetes in the 1960s had kidney failure 30 years later, compared to 31 percent of those diagnosed in the 1950s.

The high glucose (blood sugar) levels that cause diabetes can damage the membranes within the kidneys’ nephrons that are responsible for filtering the blood and forming urine. The kidneys can experience thickening and hardening (sclerosis), which weaken the ability to function.

Uncontrolled high blood pressure can also damage the kidneys. This damage can take a long time to develop and often goes unnoticed for years. People with diabetes are at particular risk for elevated blood pressure, which can cause other diabetic conditions (e.g., retinopathy, cardiovascular conditions).

More than 60 percent of patients with type 2 diabetes have high blood pressure, which puts them at greater risk for diabetic nephropathy. People diagnosed with type 2 diabetes at a young age face increased risk of nephropathy, according to recent research.

Unhealthy cholesterol levels (high “bad” LDL or insufficient “good” HDL) in people with diabetes may also lead to the development of nephropathy. Excessive “bad” cholesterol in the bloodstream causes the particles to stick to artery walls and contributes to the buildup of plaque.

Recent research shows that obesity and being overweight are major risk factors for chronic kidney disease, especially in people with high blood pressure.

Some ethnic groups appear to be predisposed to developing diabetic nephropathy. Black Americans, Hispanic Americans and Native Americans all have a higher incidence of developing renal disorders, as well as type 2 diabetes in general.

Pregnancy in diabetic women can cause nephropathy and may potentially affect the fetus. Diabetic women who wish to become pregnant are advised to have a microalbuminuria test for protein in their urine and have their kidney function checked before and during pregnancy. Pregnant women should also have their blood pressure regularly monitored as well.

Preeclampsia, a pregnancy complication involving high blood pressure and proteinuria, is more common in diabetic women than nondiabetics. Recent large-scale, long-term research indicates that an episode of preeclampsia increases the mother’s risk of kidney disease later in life.

The early stages of diabetic nephropathy often show no obvious symptoms. Symptoms may not develop until 80 percent of the kidneys have been damaged, according to the American Diabetes Association. When symptoms do appear, they may include:

• Edema (swelling) of the ankles, other extremities, face and other parts of the body
• Fatigue
• High blood pressure
• Loss of appetite
• Unintentional weight loss or weight gain
• Excessive urination (polyuria)
• Excessive thirst (polydipsia)
• Vomiting
• Headache
• Hiccups
• Pruritus (generalized itching)

During the course of the disease, small amounts of protein (microalbuminuria) and then increasing amounts of protein will leak into the urine (proteinuria). The amount can be determined only through diagnostic testing.

Diabetic retinopathy is frequently present in patients with nephropathy at the time of diagnosis, because patients often have a long history of diabetes. Measures to control nephropathy (such as maintaining healthy blood pressure and glucose levels) may help control retinopathy as well.

A crucial test for detecting diabetic nephropathy early is the microalbuminuria test of small amounts of protein in the urine. A standard urinalysis can reveal larger amounts of protein in the urine (proteinuria), but at that stage the kidneys have sustained further damage that might have been prevented or delayed.

The American Diabetes Association (ADA) recommends that people with type 2 diabetes be tested for microalbuminuria at the time of their diagnosis and then once a year thereafter. People with type 1 diabetes should be tested five years after being diagnosed and then once a year thereafter. A physician may advise more frequent testing for a patient with additional risk factors, such as elevated blood pressure.

The most basic method to test for albumin is a urine dipstick test. A coated dipstick will change color if small amounts of albumin are present. A more precise measurement can be attained by testing over a specified period of time. A patient may be asked to collect a urine sample over a four- to 24-hour period.

Other diagnostic tests for diabetic nephropathy include:  

• Serum creatinine test. A blood test that measures the level of the waste product creatinine in the blood. Creatinine comes from two sources: meat products in the diet and from wear and tear on the muscles. Almost all of it eventually ends up in a person’s urine.
  
  
• Blood urea nitrogen (BUN) test. A blood test that determines the level of urea nitrogen in the blood. Urea nitrogen is produced from a breakdown of food protein.
  
  
• Creatinine urine test. A urine test that measures the amount of creatinine in the urine.
  
  
• Creatinine clearance test. A urine test that measures the amount of fluid filtered each minute by the kidneys.
  
  
• 24-hour urine protein test. A collection of all urine produced during one day that shows how many milligrams of protein are being lost in the urine.
  
  
• Glomerular filtration rate (GFR). An indirect measurement of the amount of glomerular filtrate (a substance similar to plasma but without proteins) formed in the kidneys each minute. GFR is estimated through other tests such as creatinine clearance, serum creatinine, inulin clearance (test involving timed urine collections after intravenous administration of a sugar called inulin) or equations such as the Modification of Diet in Renal Disease (MDRD) equation. A GFR of less than 60 indicates kidney damage, according to the National Kidney Disease Education Program.

  The American Heart Association issued a recommendation in 2006 that people who have or are at risk for cardiovascular disease consider undergoing tests of kidney function, especially the MDRD, because kidney disease is a major risk factor for diseases of the heart and blood vessels.

Recent research indicates that a blood test for a protein called cystatin C can reveal increased risk for chronic kidney disease and cardiovascular disease in elderly people with no known kidney problems, and that a cholesterol blood test for a substance called apolipoprotein A-IV may predict long-term risk of progressive kidney dysfunction in people with mild to moderate kidney disease. 

As diabetic nephropathy progresses, a biopsy may be performed to determine the specific amount of kidney damage. A small tissue sample will be extracted from the kidney to be analyzed.

There are five stages that are generally recognized as belonging to the progression of nephropathy. It is important to note that acute kidney failure, which is due to such causes as trauma or poisoning, rarely progresses to end-stage renal disease (ESRD). The five stages include:

• Stage I. The kidneys filter wastes at a level that is higher than normal. This process is known as hyperfiltration. Some patients remain at this level indefinitely, while others advance to the next stage after a period of years.
  
  
• Stage II. Filtration remains elevated, and damage to the glomeruli (filtering units) begins to appear. Small amounts of the blood protein albumin can begin to leak into the urine. This condition, microalbuminuria, usually becomes progressively worse. People with diabetes who control blood pressure and keep tight control over glucose (blood sugar) levels may remain in Stage II for years.
  
  
• Stage III. Also known as overt diabetic nephropathy, it occurs when albumin in the urine increases and the kidneys’ ability to filter wastes usually begins to decrease, causing a buildup of wastes. High blood pressure (hypertension) is a frequent complication of this kidney damage. Increased levels of damage to the glomeruli are evident. Blood levels of creatinine and urea-nitrogen rise. Patients frequently remain at this stage for years.
  
  
• Stage IV. Kidney filtration is substantially impaired.  Large amounts of protein pass into the urine, and high blood pressure is almost always present. Levels of creatinine and urea-nitrogen in the blood continue to rise.
  
  
• Stage V. The final stage of kidney disease involves chronic kidney failure as part of ESRD. Filtration is seriously impaired, and the kidneys are unable to regulate the body’s balance of salt and water. Production of urine slows or stops altogether. Waste products and water accumulate in the body, leading to a potentially life-threatening overload of these substances.

There is no cure for diabetic nephropathy, but there are many steps that can be taken to slow the deterioration of kidney function. These include:

• Perform regular glucose monitoring and control glucose (blood sugar).

• Monitor blood pressure and keep it within a safe range for people with diabetes (under 130/80 mmHg).
  
  
• Lose excess weight.
  
  
• Quit smoking.
  
  
• Improve cholesterol levels. Kidney damage has been linked to elevated lipid levels. Kidney damage has been linked to elevated levels of LDL and insufficient HDL.
  
  
• Eat a healthy diet formulated to slow the speed of nephropathy. Patients may be advised to limit protein and sodium and to avoid alcohol and caffeine.

In addition, two types of blood pressure medications may be effective in treating diabetic nephropathy. Angiotensin-converting enzyme inhibitors (ACE inhibitors) have been found to help protect kidney function in people with type 1 diabetes, as well as helping to control blood pressure. Angiotensin II receptor blockers (ARBs) widen blood vessels to help lower blood pressure. The U.S. Food and Drug Administration has approved some of these drugs in the treatment of diabetic nephropathy. Sometimes a combination of ACE inhibitors and ARBs may be prescribed.

As the condition worsens, additional medications, such as calcium channel blockers or beta blockers, may be necessary to control blood pressure. In addition, diuretics may be prescribed to help flush water and sodium from the body.

Recent research has injected debate into the treatment of diabetic nephropathy and high blood pressure. Although ACE inhibitors and ARBs are generally considered to be highly desirable for treating hypertensive diabetic individuals due to kidney protection effects, other medicines that lower blood pressure (antihypertensives) may be equally effective. Individuals are advised to ask their physician about the best treatment for them.

In addition, scientists are developing potential drug treatments for diabetic nephropathy.

If damage becomes severe enough, patients may require either a kidney transplant or undergo dialysis treatment. Dialysis occurs in one of two forms:

• Hemodialysis.  A machine replaces the work of the kidneys by filtering blood. The cleaned blood is then returned to the body.
  
  
• Peritoneal dialysis. The lining of the patient’s abdomen (peritoneal membrane) is used as the filter. A catheter is surgically inserted through the wall of the abdomen, and a special dialysis solution is introduced into the abdominal cavity. This solution removes waste products and excess fluids from the bloodstream.

Patients who undergo dialysis typically need to have the procedure done three or more times a week. Dialysis treatments usually continue for life or until the patient receives a transplant. However, there have been infrequent cases of people with chronic kidney disease who regained enough kidney function to discontinue dialysis and survive.

A kidney transplant is usually more effective than dialysis. However, there are numerous factors that influence kidney transplants. The availability of and the waiting period for an appropriate kidney, the risks of rejection and the accompanying need to take anti-rejection drugs (immunosuppressives) permanently are all risks of transplantation. In addition, the new kidney will face the same strain the old ones did if glucose and blood pressure are not controlled.

Because diabetic nephropathy is progressive, the best course of action is to avoid the condition in the first place by keeping gluocse (blood sugar), blood pressure and cholesterol in safe ranges, as recommended by a physician. Healthy lifestyle habits, such as regular exercise and not smoking, are also important to prevent nephropathy.

In addition, nonsteroidal anti-inflammatory drugs (NSAIDS) are potentially toxic to the kidneys and should generally be avoided by people diagnosed with diabetic nephropathy. However, many patients who have or are at risk of cardiovascular conditions, the No. 1 killer of people with diabetes, are prescribed daily low-dose aspirin as a preventive measure.

Individuals are advised to ask their physician about the risks and benefits of aspirin therapy. Even in people who do not have diabetic nephropathy, regular long-term use of painkillers can cause a permanent form of kidney damage called analgesic nephropathy that requires dialysis or a kidney transplant, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Patients with nephropathy may be advised by a dietician to consume a diet low in protein. High-protein diets may strain the kidneys.

Kidney patients are advised to consult their physician before undergoing imaging tests using certain contrast agents. These include barium, which can worsen renal damage, and gadolinium, which has recently been linked to a rare skin disease.

Research is focusing on genetic susceptibility to kidney disease. The Joslin Diabetes Center is studying nephropathy in people with type 1 diabetes and is collaborating with the Juvenile Diabetes Research Foundation and the George Washington University Biostatistics Center in the GoKinD study, which seeks to establish a large database of DNA and clinical information from people with type 1 diabetes and their parents.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in collaboration with the National Center for Minority and Health Disparities, is studying the genetic susceptibility of ethnic populations. The Family Investigation of Nephropathy of Diabetes (FIND) is investigating the prevalence of kidney disease in family members of diabetes patients with nephropathy. Black Americans, Native Americans and Hispanic Americans appear to have an increased incidence of diabetic nephropathy and kidney disease that is unrelated to diabetes. The study will also examine the links between diabetic nephropathy and diabetic retinopathy.

The National Institutes of Health is also involved in dozens of other studies of diabetic nephropathy. These include clinical trials of several potential new drug treatments, a trial examining the possible use of COX-2 inhibitors, comparisons of the various antihypertensives and explorations of possible risk factors, including certain enzymes, oxidation and exposure to lead.

Clinical trials are investigating drugs called glycosaminoglycans that protect the kidneys. One pill that is in phase III and phase IV trials may reduce proteinuria.

Theorizing that inflammation may be an important cause of diabetic nephropathy, some researchers are studying drugs called adenosine A2 agonists that may treat nephropathy in addition to acute kidney injury.

An investigational class of drugs called aldose reductase inhibitors has shown some promise for treating diabetic complications including neuropathy, retinopathy and nephropathy.

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about diabetic nephropathy:

1. Do I have, or am I at risk of developing, diabetic nephropathy?
2. How can my diabetes affect my kidneys?
3. What condition are my kidneys in?
4. Will I see warning signs if there’s a problem with my kidneys?
5. Is my blood pressure, glucose level, cholesterol levels or weight a threat to the health of my kidneys?
6. What tests should I have to monitor my kidneys, and how often?
7. To detect nephropathy early, will my urine be tested for microalbuminuria rather than proteinuria?
8. What do my test results show?
9. If treatment is needed, what are my options, and which do you recommend?
10. If I have to take blood pressure drugs, which can help and which might hurt my kidneys?
11. Can any of my other medications affect my nephropathy?
12. What dietary changes can help treat my nephropathy?
13. What else can I do to preserve or improve the health of my kidneys?