Diabetic Nephropathy

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

Diabetic nephropathy (DN) is typically defined by macroalbuminuria—that is, a urinary albumin excretion of more than 300 mg in a 24-hour collection—or macroalbuminuria and abnormal renal function as represented by an abnormality in serum creatinine, calculated creatinine clearance, or glomerular filtration rate (GFR). Clinically, diabetic nephropathy is characterized by a progressive increase in proteinuria and decline in GFR, hypertension, and a high risk of cardiovascular morbidity and mortality.

How does Diabetes Mellitus cause Nephropathy

When our bodies digest the protein we eat, the process creates waste products. In the kidneys, millions of tiny blood vessels (capillaries) with even tinier holes in them act as filters. As blood flows through the blood vessels, small molecules such as waste products squeeze through the holes. These waste products become part of the urine. Useful substances, such as protein and red blood cells, are too big to pass through the holes in the filter and stay in the blood.

Diabetes mellitus can damage this system. High levels of blood sugar make the kidneys filter too much blood. All this extra work is hard on the filters. After many years, they start to leak and useful protein is lost in the urine. Having small amounts of protein in the urine is called microalbuminuria.

When diabetic nephropathy is diagnosed early, (during microalbuminuria), several treatments may keep diabetic nephropathy from getting worse. Having larger amounts of protein in the urine is called macroalbuminuria. When diabetic nephropathy is caught later (during macroalbuminuria), end-stage renal disease, or ESRD, usually follows.

In time, the stress of overwork causes the kidneys to lose their filtering ability. Waste products then start to build up in the blood. Finally, the kidneys fail. This failure, ESRD, is very serious. A person with ESRD needs to have a kidney transplant or to have the blood filtered by machine (dialysis).

who gets diabetic nephropathy?

There are several factors that can increase your risk of developing diabetic nephropathy. These include:

  • Having chronically elevated blood sugar levels
  • Being overweight or obese
  • Smoking
  • Having a diabetes mellitus-related vision problem (diabetic retinopathy) or nerve damage (diabetic neuropathy)
  • Having a family history of  diabetic nephropathy  or belonging to certain ethnic groups (African American, Mexican, Pima Indian) can also increase your risk of diabetic nephropathy.
 But the factors listed above are the ones you can do something about.

Signs and symptoms of Diabetic Nephropathy

Early signs and symptoms of diabetic nephropathy in patients with diabetes mellitus are typically unusual. However, a vast array of signs and symptoms listed below may manifest when diabetic nephropathy has progressed: 

  • Albumin or protein in the urine
  • High blood pressure
  • Ankle and leg swelling, leg cramps
  • Going to the bathroom more often at night
  • High levels of blood urea nitrogen (BUN) and serum creatinine
  • Less need for insulin or antidiabetic medications
  • Morning sickness, nausea, and vomiting
  • Weakness, paleness, and anemia
  • Itching

The differential diagnosis of diabetic nephropathy is vast, but includes the following in a patient with known diabetes mellitus:

  • Primary or secondary glomerular disease
  • Nephrosclerosis
  • Renovascular hypertension
  • Renal artery stenosis
  • Renal vein thrombosis
  • Multiple myeloma
  • Cholesterol embolization
  • Chronic obstruction
  • Interstitial nephritis
  • Amyloidosis

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 mellitus to have regular testing.

If you have type 1 diabetes mellitus, get a urine test every year after you have had diabetes mellitus for 5 years.

If your child has diabetes mellitus, yearly testing should begin when your child is 10 years old and has had diabetes mellitus for 5 years.

If you have type 2 diabetes mellitus, start yearly testing at the time you are diagnosed with diabetes mellitus.

Can I prevent Diabetic Nephropathy?

Diabetic nephropathy can be prevented by keeping blood sugar in your target range. Research has shown that tight blood sugar control reduces the risk of microalbuminuria by one third. In people who already had microalbuminuria, the risk of progressing to macroalbuminuria was cut in half. Other studies have suggested that tight control can reverse microalbuminuria.

How can i treat Diabetic Nephropathy?

People with diabetes mellitus often focus on keeping their blood sugar levels in the right ranges. And while it is important to control blood sugar, it turns out that controlling blood pressure is at least as important. That's because high blood sugar and high blood pressure work in concert to damage the blood vessels and organ systems. (See "Treatment of diabetic nephropathy".)

For these reasons, the most important things you can do to stall diabetic nephropathy and protect against other diabetes mellitus complications are to:

  • Make healthy lifestyle choices
  • Keep your blood sugar as close to normal as possible (see 'Manage blood sugar levels' below).
  • Keep your blood pressure below 130/80, if possible (see 'Manage high blood pressure' below).
  • Lifestyle changes — Changing your lifestyle can have a big impact on the health of your kidneys. The following measures are recommended for everyone, but are especially important if you have diabetic nephropathy:
  • Limit the amount of salt you eat (see "Patient information: Low sodium diet (Beyond the Basics)")
  • If you smoke, quit smoking (see "Patient information: Quitting smoking (Beyond the Basics)")
  • Lose weight if you are overweight (see "Patient information: Diet and health (Beyond the Basics)" and "Patient information: Exercise (Beyond the Basics)" and "Patient information: Weight loss treatments (Beyond the Basics)")

Manage blood sugar levels — Keeping blood sugars close to normal can help prevent the long-term complications of diabetes mellitus. For most people, a target for fasting blood glucose and for blood glucose levels before each meal is 80 to 120 mg/dL (4.4 to 6.6 mmol/L); however, these targets may need to be individualized. (See "Patient information: Self-blood glucose monitoring in diabetes mellitus (Beyond the Basics)".)

A blood test called A1C is also used to monitor blood sugar levels; the result provides an average of blood sugar levels over the last one to three months. An A1C of 7 percent or less is usually recommended; this corresponds to an average blood glucose of 150 mg/dL (8.3 mmol/L) (table 1). Even small decreases in the A1C lower the risk of diabetes mellitus-related complications to some degree.

Manage high blood pressure — Many people with diabetes mellitus have hypertension (high blood pressure). Although high blood pressure causes few symptoms, it has two negative effects: it stresses the cardiovascular system and speeds the development of diabetic complications of the kidney and eye. A healthcare provider can diagnose high blood pressure by measuring blood pressure on a regular basis. (See "Patient information: High blood pressure in adults (Beyond the Basics)".)

The treatment of high blood pressure varies. If you have mild hypertension, your healthcare provider may recommend weight loss, exercise, decreasing the amount of salt in the diet, quitting smoking, and decreasing alcohol intake. These measures can sometimes reduce blood pressure to normal. (See "Patient information: High blood pressure, diet, and weight (Beyond the Basics)".)

If these measures are not effective or your blood pressure needs to be lowered quickly, your provider will likely recommend one of several high blood pressure medications. Your provider can discuss the pros and cons of each medication and the goals of treatment. (See "Patient information: High blood pressure treatment in adults (Beyond the Basics)".)

A blood pressure reading below 130/80 is the recommended goal for most people with diabetic nephropathy.

Blood pressure medications — Most people with diabetic nephropathy need at least one medication to lower their blood pressure. Several medications can be used for this purpose, but a medication known as an angiotensin converting enzyme inhibitor (abbreviated ACE inhibitor) or a related drug known as an angiotensin receptor blocker (ARB) are used most commonly. ACE inhibitors are generally used first because they have been available longer than ARBs.

ACE inhibitors and ARBs are particularly useful for people with diabetic nephropathy because they decrease the amount of protein in the urine and can prevent or slow the progression of diabetes mellitus-related nephropathy. In fact, the kidney benefits of ACE inhibitors and ARBs are so robust that healthcare providers sometimes prescribe them for people with diabetic nephropathy who have normal blood pressure.

Still, despite their kidney-protecting abilities, ACE inhibitors and ARBs do have their downsides. For instance, ACE inhibitors cause a persistent dry cough in 5 to 20 percent of the people who take them. Some people get used to the cough; others find it so disruptive that they cannot continue taking an ACE inhibitor. For them, ARBs are often a good alternative, because ARBs are less likely to cause a cough.

In rare cases, you can have more serious side effects with ACE inhibitors and ARBs. These include a decrease in kidney function or a condition called hyperkalemia, in which too much potassium accumulates in the blood. To monitor for these and other side effects, healthcare providers sometimes run blood tests soon after starting these drugs. In some people, the medications will need to be stopped.

More information on the risks and side effects of ACE inhibitors and ARBs is available (see "Major side effects of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers").

Monitor for signs of change — After beginning treatment and lifestyle changes to stall diabetic nephropathy, you will need to have repeat urine and blood tests to determine if urine protein levels have improved. If the urine protein levels have not improved or your kidney function has worsened, your healthcare provider may need to adjust your medications or recommend other strategies to protect your kidneys.

Kidney Failure

Once kidneys fail, dialysis is necessary. The person must choose whether to continue with dialysis or to get a kidney transplant. This choice should be made as a team effort. The team should include the doctor and diabetes mellitus educator, a nephrologist (kidney doctor), a kidney transplant surgeon, a social worker, and a psychologist.

Pregnancy and Diabetic Nephropathy

If you have diabetes mellitus and are interested in getting pregnant, it is important to talk with your healthcare provider well in advance, especially if you have diabetic nephropathy. Diabetes mellitus and its attendant problems can increase the risk of complications in pregnancy, especially in women with decreased kidney function. However, many women with mild diabetic nephropathy have normal pregnancies and healthy babies.

To ensure the best outcome with a pregnancy, the most important thing you can do is to keep your blood sugar and blood pressure under tight control. However, women who are pregnant or attempting to get pregnant should not take ACE inhibitors or ARBs, as these drugs can cause birth defects. Instead, other medications (such as calcium channel blockers) are used during pregnancy to keep the blood pressure in check.

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