Each kidney is made of more than a million units called nephrons. Each nephron has a tuft of blood vessels called a glomerulus. The glomerulus filters blood and forms urine, which drains down into collecting ducts to the ureter.

The earliest detectable change in the course of diabetic nephropathy is a thickening in the glomerulus. At this stage, the kidney may start allowing more albumin (protein) than normal in the urine, and this can be detected by sensitive tests for albumin. This stage is called "microabuminuria" (micro refers to the small amounts of albumin).

As diabetic nephropathy progresses, increasing numbers of glomeruli are destroyed. Now the amounts of albumin being excreted in the urine increases, and may be detected by ordinary urinalysis techniques. At this stage, a kidney biopsy clearly shows diabetic nephropathy.

Protein may appear in the urine for 5 to 10 years before other symptoms develop. High blood pressure often accompanies diabetic nephropathy. Over time, the kidney's ability to function starts to decline. Diabetic nephropathy may eventually lead to chronic kidney failure. The disorder continues to progress toward end-stage kidney disease, usually within 2 to 6 years after the appearance of high protein in the urine (proteinuria).

Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage kidney disease in the United States. People with both type 1 and type 2 diabetes are at risk. The risk is higher if blood-glucose levels are poorly controlled. However, once nephropathy develops, the greatest rate of progression is seen in patients with poor control of their blood pressure.

Diabetic nephropathy is generally accompanied by other diabetes complications including hypertension, retinopathy, and vascular (blood vessel) changes, although these may not be obvious during the early stages of nephropathy. Nephropathy may be present for many years before high protein in the urine or chronic kidney failure develop.

Throughout its early course, diabetic nephropathy has no symptoms. Symptoms develop in late stages and may be a result of excretion of high amounts of protein in the urine or due to renal failure:

• swelling -- usually around the eyes in the mornings; later, general body swelling may result
• foamy appearance or excessive frothing of the urine
• unintentional weight gain (from fluid accumulation)
• swelling of the legs
• poor appetite
• nausea and vomiting
• general ill feeling
• fatigue
• headache
• frequent hiccups
• generalized itching
  

The first laboratory abnormality is a positive microalbuminuria test. This means you are very likely to develop diabetic nephropathy.

Most often, the diagnosis is suspected when a routine urinalysis of a person with diabetes shows too much protein in the urine (proteinuria). The urinalysis may also show glucose in the urine, especially if blood glucose is poorly controlled.
There may or may not be signs of other diabetic complications. High blood pressure may be present or develop rapidly and may be difficult to control. Serum creatinine and BUN may increase as kidney damage progresses.

A kidney biopsy confirms the diagnosis. Most nephrologists do not need to perform the biopsy if the case is straightforward, with a documented progression of proteinuria over time and presence of diabetic retinopathy on examination of the retina of the eyes. Should there be any doubt in the diagnosis, a biopsy may be performed to confirm the diagnosis and to study the extent of the disease.

This disease may also alter the results of the following tests:

• protein electrophoresis - urine
• creatinine - urine
• 24-hour urine protein

The goals of treatment are to slow the progression of kidney damage and control related complications.

The main treatment, once proteinuria is established, is angiotensin converting enzyme (ACE) inhibitors. This class of drugs reduces urine protein levels and slows the progression of diabetic nephropathy. Many studies have shown that related drugs, angiotensin receptor blockers (ARBs), have a similar benefit. In fact, a combination may be best.

Blood-glucose levels should be closely monitored and controlled. This may slow the progression of the disorder, especially in the very early ("microalbuminuria") stages.

Medications to manage diabetes include hypoglycemic pills and insulin injections. Your blood glucose must be monitored and the dose of insulin adjusted as needed. As kidney failure progresses, less insulin is excreted, so smaller doses may be needed to control glucose levels.

The diet may be modified (see diet for diabetics) to help control blood-sugar levels.

High blood pressure should be aggressively treated with antihypertensive medications. Uncontrolled high blood pressure will worsen kidney, eye, and blood vessel damage in the body. Controlling your high blood pressure is the most effective way of slowing kidney damage from diabetic nephropathy. It is also very important to control lipid levels, maintain a healthy weight, and engage in regular physical activity.

Contrast dyes that contain iodine are excreted through the kidney. They may worsen an already reduced glomerular filtration rate, and should be avoided if possible. If they must be used, fluids should be adequate to allow their rapid excretion.

Commonly used non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen, or Cox-2 inhibitors like Celebrax or Vioxx, may injure the weakened kidney. A physician must always be consulted before using any drugs, but especially these.

Urinary tract and other infections are common and can be treated with appropriate antibiotics.

Dialysis may be necessary once end-stage renal disease develops. At this stage, a
kidney transplant must be considered. Another option for type 1 diabetes patients is a combined kidney-pancreas transplant.

Diabetic nephropathy continues to get gradually worse. Complications of chronic kidney failure are more likely to occur earlier, and progress more rapidly, when it is caused by diabetes than other causes.

Even after initiation of dialysis or after transplantation, people with diabetes tend to do worse than those without diabetes.

• hypoglycemia (from decreased excretion of insulin)
• rapidly progressing chronic kidney failure
• end-stage kidney disease
• hyperkalemia
• severe hypertension
• complications of dialysis
• complications of kidney transplant
• coexistence of other diabetes complications
• peritonitis (if peritoneal dialysis used)
• increased infections

Call your health care provider if your health care provider if you have diabetes and a routine urinalysis shows protein.

Call your health care provider if you develop symptoms of diabetic nephropathy, or if new symptoms develop, including little or no urine output.