Diabetic Nephropathy

Topic Overview

What is diabetic nephropathy?

Nephropathy means kidney disease or damage. Diabetic nephropathy is damage to your kidneys caused by diabetes. In severe cases it can lead to kidney failure. But not everyone with diabetes has kidney damage.

What causes diabetic nephropathy?

The kidneys have many tiny blood vessels that filter waste from your blood. High blood sugar from diabetes can destroy these blood vessels. Over time, the kidney isn't able to do its job as well. Later it may stop working completely. This is called kidney failure.

For reasons doctors don't yet understand, only some people with diabetes get kidney damage. Out of 100 people with diabetes, as many as 40 will get kidney damage.¹

Certain things make you more likely to get diabetic nephropathy. If you also have high blood pressureor high cholesterol, or if you smoke, your risk is higher. Also, Native Americans, African Americans, and Hispanics (especially Mexican Americans) have a higher risk.²

What are the symptoms?

There are no symptoms in the early stages. So it's important to have regular urine tests to find kidney damage early. Sometimes early kidney damage can be reversed.

The first sign of kidney damage is a small amount of protein in the urine, which is found by a simple urine test.

As damage to the kidneys gets worse, your blood pressure rises. Your cholesterol and triglyceride levels rise too. As your kidneys are less able to do their job, you may notice swelling in your body, at first in your feet and legs.

How is diabetic nephropathy diagnosed?

The problem is diagnosed using simple tests that check for a protein called albumin in the urine. Urine does not usually contain protein. But in the early stages of kidney damage-before you have any symptoms-some protein may be found in your urine, because your kidneys aren't able to filter it out the way they should.

Finding kidney damage early can keep it from getting worse. So it's important for people with diabetes to have regular testing.

• If you have type 1 diabetes, get a urine test every year after you have had diabetes for 5 years.
• If your child has diabetes, yearly testing should begin at puberty.
• If you have type 2 diabetes, start yearly testing at the time you are diagnosed with diabetes.

How is it treated?

The main treatment is medicine to lower your blood pressure and prevent or slow the damage to your kidneys. These medicines include:

• Angiotensin-converting enzyme inhibitors, also called ACE inhibitors.
• Angiotensin II receptor blockers, also called ARBs.

You may need to take more than one medicine, especially if you also have high blood pressure.

And there are other steps you can take. For example:

• Work with your doctor to keep your blood pressure down, usually below 130/80.
• Work with your doctor to keep your cholesterol level as close to normal as you can. You may need to take medicines for this.
• Keep your heart healthy by eating a low-fat diet and exercising regularly. Preventing heart disease is important, because people with diabetes are 2 to 4 times more likely to die of heart and blood vessel diseases. And people with kidney disease are at an even higher risk for heart disease.
• Watch how much protein you eat. Eating too much is hard on your kidneys. If diabetes has affected your kidneys, limiting how much protein you eat may help you preserve kidney function. Talk to your doctor or dietitian about how much protein is best for you.
• Watch how much salt you eat. Eating less salt helps keep high blood pressure from getting worse.
• Don't smoke or use other tobacco products.

How can diabetic nephropathy be prevented?

The best way to prevent kidney damage is to keep your blood sugar under tight control. You do this by staying at a healthy weight, exercising regularly, and taking your medicines as directed.

At the first sign of protein in your urine, you can take high blood pressure medicines to keep kidney damage from getting worse.

Frequently Asked Questions

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Symptoms

There are no symptoms in the early stages of diabetic nephropathy. The only sign of kidney damage may be small amounts of protein leaking into the urine (microalbuminuria). Normally, protein is not found in urine except during periods of high fever, strenuous exercise, pregnancy, or infection.

In people with type 1 diabetes, diabetic nephropathy usually develops 5 to 10 years after the onset of diabetes. People with type 2 diabetes may find out that they already have a small amount of protein in the urine (microalbuminuria) at the time diabetes is diagnosed, because they may have had diabetes for several years.

As diabetic nephropathy progresses, your kidneys cannot do their job as well. Your kidneys cannot clear toxins or drugs from your body as well. And your kidneys cannot balance the chemicals in your blood very well. You may:

• Lose more protein in your urine (macroalbuminuria, also known as overt nephropathy).
• Have higher blood pressure.
• Have higher cholesterol and triglyceride levels.

You may have symptoms if your nephropathy gets worse. These symptoms include:

• Swelling (edema), first in the feet and legs and later throughout your body.
• Poor appetite.
• Weight loss.
• Weakness.
• Feeling tired or worn out.
• Nausea or vomiting.
• Trouble sleeping.

See the topic Chronic Kidney Disease for more information.

If the kidneys are severely damaged, blood sugar levels may drop because the kidneys cannot remove excess insulin or filter oral medicines that increase insulin production, such as glipizide (Glucotrol) or glyburide (for example, Micronase).

Exams and Tests

Diabetic nephropathy is diagnosed using tests that check for a protein (albumin) in the urine, which is an indicator of kidney damage. Your urine will be checked for protein (urinalysis) when you are diagnosed with diabetes.

Microalbumin urine tests can detect very small amounts of protein in the urine that cannot be detected by a routine urine test, allowing early detection of nephropathy. Early detection is important, to prevent further damage to the kidneys. The results of two tests, done within a 3- to 6-month period, are needed to diagnose nephropathy.

When to begin checking for protein in the urine depends on the type of diabetes you have. After testing begins, it should be done every year.¹

A microalbuminuria dipstick test is a simple test that can detect small amounts of protein in the urine (microalbuminuria, also called proteinuria). The strip changes color if protein is present, providing an estimate of the amount of protein. A spot urine test for microalbuminuria is a more precise laboratory test that can measure the exact amount of protein in a urine sample. Either of these tests may be used to test your urine for protein.

You will also have a creatinine test done every year. The creatinine test is a blood test that shows how well your kidneys are working.

If your doctor suspects that the protein in your urine may be caused by a disease other than diabetes, other blood and urine tests may be done. You may have a small sample of kidney tissue removed and examined (kidney biopsy).

Other tests

It is important to check your blood pressure regularly, both at home and in your doctor's office, because blood pressure rises as kidney damage progresses. About one-third of people with type 2 diabetes have high blood pressure at the time diabetes is diagnosed. The American Diabetes Association recommends a target blood pressure of less than 130/80 millimeters of mercury (mm Hg).¹ The level recommended by other organizations may vary. Talk with your doctor about what your target blood pressure level should be. Keeping your blood pressure at or below this target can prevent or slow kidney damage.

Blood levels of cholesterol and triglycerides also should be checked regularly to see whether diabetes, nephrotic syndrome, or other factors are raising your blood cholesterol level. High cholesterol can increase the risk of hardening of the arteries (atherosclerosis), possibly leading to heart disease, peripheral arterial disease, and stroke.

Treatment Overview

Diabetic nephropathy is treated with medicines that lower blood pressure and protect the kidneys. These medicines may reverse kidney damage and are started as soon as any amount of protein is found in the urine (microalbuminuria). The use of these medicines before nephropathy occurs may also help prevent nephropathy in people who have normal blood pressure.^{3, 4}

If you have high blood pressure, two or more medicines may be needed to lower your blood pressure enough to protect the kidneys. Medicines are added one at a time as needed. The American Diabetes Association recommends a target blood pressure of less than 130/80 millimeters of mercury (mm Hg).¹ The level recommended by other organizations may vary. Talk with your doctor about what your target blood pressure level should be. For more information on blood pressure medicines, see the topic High Blood Pressure (Hypertension).

If you take other medicines, avoid ones that damage or stress the kidneys, especially nonsteroidal anti-inflammatory drugs (NSAIDs).

It is also important to keep your blood sugar as close to normal as possible. Maintaining blood sugar levels at a close to normal level prevents damage to the small blood vessels in the kidneys.

Limiting the amount of salt in your diet can help keep your high blood pressure from becoming worse. You may also want to restrict the amount of protein in your diet. If diabetes has affected your kidneys, limiting how much protein you eat may help you preserve kidney function. Talk to your doctor or dietitian about how much protein is best for you.

People with diabetes are 2 to 4 times more likely than people who don't have diabetes to die of heart and blood vessel diseases. Using low-dose aspirin therapy and eating a low-fat diet can help prevent heart attack, stroke, and other large blood vessel disease (macrovascular disease).⁵

Initial treatment

Medicines that are used to treat diabetic nephropathy are also used to control blood pressure. If you have a very small amount of protein in your urine, these medicines may reverse the kidney damage. Medicines used for initial treatment of diabetic nephropathy include:

• Angiotensin-converting enzyme (ACE) inhibitors, such as captopril, lisinopril, ramipril, and enalapril. ACE inhibitors have been shown to protect kidney function in people with type 1 diabetes, even in those who do not have high blood pressure.⁶ ACE inhibitors can lower the amount of protein being lost in the urine. Also, they may reduce your risk of heart and blood vessel (cardiovascular) disease. One study found that ramipril cut the risk of cardiovascular disease in people with diabetes (type 1 and type 2 diabetes) by 25% to 30%.⁷
• Angiotensin II receptor blockers (ARBs), such as candesartan cilexetil, irbesartan, losartan potassium, and telmisartan. You may be given both an ACE inhibitor and an ARB. The combination of these medicines may provide greater protection for your kidneys than either medicine alone.

If you also have high blood pressure, two or more medicines may be needed to lower your blood pressure enough to protect your kidneys. Medicines are added one at a time as needed. The American Diabetes Association recommends a target blood pressure of less than 130/80 millimeters of mercury (mm Hg).¹

If you take other medicines, avoid ones that damage or stress the kidneys, especially nonsteroidal anti-inflammatory drugs (NSAIDs).

It is also important to maintain your blood sugar as close to normal as possible to prevent damage to the small blood vessels in the kidneys. The American Diabetes Association recommends that you keep your blood sugar levels at:¹

• 70 mg/dL to 130 mg/dL before meals and 110 mg/dL to 150 mg/dL at bedtime.
• Less than 180 mg/dL 1 to 2 hours after meals.

People with diabetes are 2 to 4 times more likely than people who don't have diabetes to die of heart and blood vessel diseases. Eating a low-fat diet can help prevent heart attack, stroke, and other large blood vessel disease (macrovascular disease).⁵

Limiting the amount of salt in your diet can help keep your high blood pressure from becoming worse. You will also want to restrict the amount of protein in your diet. If diabetes has affected your kidneys, limiting how much protein you eat may help you preserve kidney function. Talk to your doctor or dietitian about how much protein is best for you.

Ongoing treatment

As diabetic nephropathy progresses, blood pressure usually rises, making it necessary to add more medicine to control blood pressure. The goal set by the American Diabetes Association is to keep your blood pressure less than 130/80 mm Hg, if possible, to protect your kidneys. The level recommended by other organizations may vary. Talk with your doctor about what your target blood pressure level should be.

Your doctor may advise you to take the following medicines that lower blood pressure. You may need to take different combinations of these medicines to best control your blood pressure. By lowering your blood pressure, you may reduce your risk of kidney damage. Medicines include:

• A combination of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). A combination of these medicines may be more effective in controlling blood pressure than either used alone.
• Calcium channel blockers lower blood pressure by making it easier for blood to flow through the vessels. Examples include diltiazem (such as Cardizem SR, Dilacor XR, or Tiazac), verapamil (such as Calan SR or Isoptin SR), amlodipine (such as Norvasc), and nifedipine (such as Adalat or Procardia XL).
• Diuretics. Medicines such as chlorthalidone, hydrochlorothiazide, or spironolactone help lower blood pressure by removing sodium and water from the body.
• Beta-blockers lower blood pressure by slowing down your heart beat and reducing the amount of blood pumped with each heart beat. Examples include atenolol (Tenormin), carvedilol (Coreg), or metoprolol (such as Lopressor).

If you take other medicines, avoid ones that may damage or stress the kidneys, especially nonsteroidal anti-inflammatory drugs (NSAIDs).

It is also important to maintain your blood sugar as close to normal as possible to prevent damage to the small blood vessels in the kidneys. The American Diabetes Association recommends that you keep your blood sugar levels at:¹

• 70 mg/dL to 130 mg/dL before meals and 110 mg/dL to 150 mg/dL at bedtime.
• Less than 180 mg/dL 1 to 2 hours after meals.

People with diabetes are 2 to 4 times more likely than people who don't have diabetes to die of heart and blood vessel diseases. Eating a low-fat diet can help prevent heart attack, stroke, and other large blood vessel disease (macrovascular disease).⁵

Limiting the amount of salt in your diet can help keep your high blood pressure from becoming worse. You will also want to restrict the amount of protein in your diet. If diabetes has affected your kidneys, limiting how much protein you eat may help you preserve kidney function. Talk to your doctor or dietitian about how much protein is best for you.

People who have diabetic nephropathy also have an increased risk of illness and death from cardiovascular disease, so it is important to work with your doctor to reduce your risk of heart problems. Strategies include keeping your cholesterol at a normal level, using low-dose aspirin therapy, getting regular exercise, and not smoking.

Treatment if the condition gets worse

If damage to the blood vessels in the kidneys continues, kidney failure eventually develops. When that occurs, it is likely that you will need dialysis treatment (renal replacement therapy)-an artificial method of filtering the blood-or a kidney transplant to survive. For more information, see the topic Chronic Kidney Disease.

What to think about

Diabetic nephropathy can get worse during pregnancy and can affect the growth and development of the fetus. If your nephropathy is not severe, your kidney function may return to its prepregnancy level after the baby is born. If you have severe nephropathy, pregnancy may lead to permanent worsening of your kidney function.⁸

If you have nephropathy and are pregnant or are planning to become pregnant, talk with your doctor about which medicines you can take. You may not be able to take some medicines (for example, angiotensin-converting enzyme [ACE] inhibitors, such as captopril, lisinopril, ramipril, or enalapril) during pregnancy, because they may harm your developing baby. Talk to your doctor about your medicines and your plan to become pregnant.

Prevention

Prevention is the best way to avoid kidney damage from diabetic nephropathy.

• Keep your blood glucose levels as close to normal as possible. Manage your blood sugar by eating a balanced diet, taking your medicines (insulin or oral medicines), and getting regular exercise. The American Diabetes Association recommends that you keep your blood sugar levels at:¹
  • 70 mg/dL to 130 mg/dL before meals and 110 mg/dL to 150 mg/dL at bedtime.
  • Less than 180 mg/dL 1 to 2 hours after meals.
  Your doctor will want you to check your blood sugar several times each day. For more information, see:

  Diabetes: Checking your blood sugar.

• Have yearly testing for protein in your urine.
  • If you have type 1 diabetes, begin urine tests for protein after you have had diabetes for 5 years.
  • Children with type 1 diabetes should begin yearly urine protein screening beginning at puberty.
  • If you have type 2 diabetes, begin screening at the time diabetes is diagnosed.
• Keep your blood pressure at less than 130/80 mm Hg with medicine, diet, and exercise. Learn to check your blood pressure at home. For more information, see:

  Chronic kidney disease: Changing your diet.

  High blood pressure: Checking your blood pressure at home.

• Stay at a healthy weight. This can help you prevent other diseases, such as high blood pressure and heart disease. For more information, see the topic Weight Management.
• Follow the nutrition guidelines for hypertension (including the Dietary Approaches to Stop Hypertension, or DASH, diet). For more information, see:

  High blood pressure: Using the DASH diet.

• Do not smoke or use other tobacco products. For more information, see the topic Quitting Smoking.

If you already have diabetic nephropathy, you may be able to slow the progression of kidney damage by:

• Avoiding dehydration by promptly treating other conditions-such as diarrhea, vomiting, or fever-that can cause it. Be especially careful during hot weather or when you exercise.
• Reducing your risk of heart disease. Lifestyle changes such as eating a low-fat diet,quitting smoking , and getting regular exercise can help reduce your overall risk of developing heart disease and stroke. For more information, see the topics Healthy Eating, Fitness, and Quitting Smoking.
• Treating other conditions that may block the normal flow of urine out of the kidneys, such as kidney stones, an enlarged prostate, or bladder problems.
• Not using medicines that may be harmful to your kidneys, especially nonsteroidal anti-inflammatory drugs (NSAIDs). Be sure that your doctor knows about all prescription, nonprescription, and herbal medicines you are taking.
• Avoiding X-ray tests that require IV contrast material, such as angiograms, intravenous pyelography (IVP), and some CT scans. IV contrast can cause further kidney damage. If you do need to have these types of tests, make sure your doctor knows that you have diabetic nephropathy.
• Avoiding situations where you risk losing large amounts of blood, such as unnecessary surgeries. Do not donate blood or plasma.
• Lowering your blood pressure, because high blood pressure can make kidney damage even worse.
• Checking with your doctor to find out if it is safe for you to drink alcohol. If you do drink alcohol, have no more than 1 drink a day. Limiting alcohol can lower your blood pressure and lower your risk of kidney damage.

Home Treatment

If you have diabetes, work with your doctor to keep your blood sugar levels as close to normal as possible. By managing your blood sugar, you can reduce the chances of developing nephropathy, or you can slow the disease if you already have it.¹ Your doctor will want you to check your blood sugar several times each day. For more information, see:

Diabetes: Checking your blood sugar.

Other steps you can take include the following:

• Check your blood pressure often, and also have it checked at your doctor's office. The American Diabetes Association recommends a target blood pressure of less than 130/80 millimeters of mercury (mm Hg).¹ The level recommended by other groups may vary. Talk with your doctor about the target blood pressure that is right for you. Learn to check your blood pressure at home. For more information, see:

  High blood pressure: Checking your blood pressure at home.

• Be sure to take your blood pressure medicines as prescribed.
• Don't take medicines that damage or stress the kidneys, especially nonsteroidal anti-inflammatory drugs (NSAIDs).
• Follow the nutrition guidelines for hypertension (including the Dietary Approaches to Stop Hypertension, or DASH, diet). For more information, see:

  High blood pressure: Using the DASH diet.

• Stay at a healthy weight for your height and age by eating a well-balanced diet and exercising regularly. A low-fat diet and regular exercise also will lower your risk of heart and blood vessel (cardiovascular) disease. See the body mass index (BMI) chart for adults or the same chart in metric to determine your healthy weight.
• Do not smoke or use other tobacco products. People with diabetes who smoke raise their risk of nephropathy, cardiovascular disease, and other complications of diabetes.
• Eat a moderate amount of protein. If you have nephropathy, your doctor may recommend limiting protein. Limiting how much protein you eat may help you preserve kidney function. Talk to your doctor or dietitian about how much protein is best for you.
• Limit salt. Your doctor may recommend that you cut back on salt because it may make your high blood pressure worse.

What to Think About

If your diabetic nephropathy becomes worse and kidney failure develops, you may need to follow a specific diet. A dietitian can help you understand the requirements of this diet and help you make healthy choices. For more information, see:

Chronic kidney disease: Changing your diet.

Other Places To Get Help

Organizations

Related Information

• Chronic Kidney Disease
• Diabetic Neuropathy
• Diabetic Retinopathy
• High Blood Pressure (Hypertension)
• Low-Dose Aspirin Therapy
• Nephrotic Syndrome
• Type 1 Diabetes
• Type 2 Diabetes: Living With Complications
• Type 2 Diabetes: Living With the Disease

References

Citations

1. American Diabetes Association (2008). Standards of medical care in diabetes. Clinical Practice Recommendations 2008. Diabetes Care, 31(Suppl 1): S12-S54.

2. American Diabetes Association (2004). Nephropathy in diabetes. Clinical Practice Recommendations 2004. Diabetes Care, 27(Suppl 1): S79-S83.

3. Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group (2001). Beneficial effects of intensive therapy of diabetes during adolescence: Outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT). Journal of Pediatrics, 139(6): 804-812.

4. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2002). Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA, 287(19): 2563-2569.

5. Van Dam RM, et al. (2002). Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Annals of Internal Medicine, 136(3): 201-209.

6. ACE Inhibitors in Diabetic Nephropathy Trialist Group (2001). Should all patients with type 1 diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors? Annals of Internal Medicine, 134(5): 370-379.

7. Gerstein HC, et al. (2000). Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: Results of the HOPE study and MICRO-HOPE substudy. Lancet, 355(9200): 253-259.

8. American Diabetes Association (2004). Preconception care of women with diabetes. Clinical Practice Recommendations 2004. Diabetes Care, 27(Suppl 1): S76-S78.

Other Works Consulted

• American Diabetes Association (2005). Diabetes complications and prevention. In American Diabetes Association Complete Guide to Diabetes, 4th ed., pp. 320-324. Alexandria, VA: American Diabetes Association.

• Bakris GL (2003). The evolution of treatment guidelines for diabetic nephropathy. Postgraduate Medicine, 113(5): 35-50.

• Brownlee M, et al. (2008). Complications of diabetes mellitus. In PR Larsen et al., eds., Williams Textbook of Endocrinology, 11th ed., pp. 1417-1498. Philadelphia: Saunders Elsevier.

• Molitch ME, Genuth S (2006). Complications of diabetes mellitus. In DC Dale, DD Federman, eds., ACP Medicine, section 9, chap. 3. New York: WebMD.

• Parving H, et al. (2008). Diabetic nephropathy. In BM Brenner, ed., Brenner and Rector's The Kidney, 8th ed., vol. 2, pp. 1265-1298. Philadelphia: Saunders Elsevier.

• Shlipak M (2008). Diabetic nephropathy, search date November 2006. Online version of BMJ Clinical Evidence. Also available online: http://www.clinicalevidence.com.

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