Male urinary system
Male urinary system
Pancreas and kidneys
Pancreas and kidneys

Diabetic nephropathy/Sclerosis

Definition:
A kidney disorder that is a complication of diabetes, characterized by proteinuria and progressive reduction in kidney function.

Alternative Names:
Kimmelstiel-Wilson disease; Diabetic glomerulosclerosis; Diabetic kidney disease

Causes, incidence, and risk factors:
Uncontrolled diabetes causes damage to many tissues of the body. Kidney damage caused by diabetes most often involves thickening and hardening (sclerosis) of the internal kidney structures, particularly the glomerulus (kidney membrane). Kimmelstiel-Wilson disease is the unique microscopic characteristic of diabetic nephropathy in which sclerosis of the glomeruli is accompanied by nodular deposits of hyaline.

The glomeruli are the site where blood is filtered and urine is formed. They act as a selective membrane, allowing some substances to be excreted in the urine and other substances to remain in the body. As diabetic nephropathy progresses increasing numbers of glomeruli are destroyed, resulting in impaired kidney functioning. Filtration slows and protein (which is normally retained in the body) may leak in the urine. Protein may appear in the urine for 5 to 10 years before other symptoms develop. Hypertension often accompanies diabetic nephropathy.

Diabetic nephropathy may eventually lead to the nephrotic syndrome (a group of symptoms characterized by excessive loss of protein in the urine) and chronic renal failure. The disorder continues to progress, with end-stage renal disease developing, usually within 2 to 6 years after the appearance of renal insufficiency with proteinuria.

The mechanism that causes diabetic nephropathy is unknown. It may be caused by inappropriate incorporation of glucose molecules into the structures of the basement membrane and the tissues of the glomerulus. Hyperfiltration (increased urine production) associated with high blood sugar levels may be an additional mechanism of disease development.

The diabetic nephropathy is the most common cause of chronic renal failure and end stage renal disease in the United States. About 40% of people with insulin-dependent diabetes will eventually develop end-stage renal disease. 80% of people with diabetic nephropathy as a result of IDDM have had this diabetes for 18 or more years. At least 20% of people with NIDDM will develop diabetic nephropathy, but the time course of development of the disorder is much more variable than in IDDM. The risk is related to the control of the blood-glucose levels. Risk is higher if glucose is poorly controlled than if the glucose level is well controlled.

Diabetic nephropathy is generally accompanied by other diabetic 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 nephrotic syndrome or chronic renal failure develops. Nephropathy is often diagnosed when routine urinalysis shows protein in the urine.
Symptoms:
There may be no symptoms for many years.

Additional symptoms that may be associated with this disease:
Signs and tests:
The first laboratory abnormality is a positive microalbuminuria test. The initial diagnosis is commonly suspected when routine urinalysis of a person with diabetes shows protein in the urine (proteinuria). There may or may not be signs of other diabetic complications. Hypertension may be present or develop rapidly and may be difficult to control. Examination of the retina of the eyes (fundoscopy) may show diabetic retinopathy.

Urinalysis shows protein, mostly representing the protein albumin. It may also show glucose in the urine, especially if blood glucose is poorly controlled.

Serum creatinine and BUN may increase as kidney damage progresses.

A kidney biopsy confirms the diagnosis and may be performed to evaluate the extent of diabetic nephropathy.

This disease may also alter the results of the following tests:
Treatment:
The disorder is progressive. The goals of treatment are to slow the progression of kidney damage and control related complications. The main treatment once proteinuria is found in diabetics is angiotensin converting enzyme inhibitors (ACEI). This class of drugs reduces urine protein excretion and slows progression of diabetic nephropathy.

Blood-glucose should be monitored regularly. Close control of the blood-glucose level may slow the progression of the disorder.

Medications used to manage diabetes may include oral hypoglycemic agents and/or insulin injections. The blood-glucose must be monitored and the dosage of insulin is adjusted as needed. Progression of kidney failure reduces the excretion of insulin, so smaller and smaller doses may be needed to control glucose levels.

Diet may be modified (diet for diabetics or other calorie, protein, and fat regulated diet) to help control blood-sugar levels.

Hypertension should be aggressively treated with antihypertensive medications. Uncontrolled hypertension will worsen kidney, eye, and vascular damage in the body. Control of hypertension is the most effective way of slowing kidney damage from diabetic nephropathy.

Dialysis may be necessary early in the course of renal failure.

Kidney transplant is commonly used in the treatment of diabetic nephropathy.

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.

Urinary-tract and other infections are common and should be treated effectively with appropriate antibiotics.

Renal failure should be treated as appropriate. A high serum potassium level (hyperkalemia) is common and should be treated with appropriate medications and/or dialysis.
Expectations (prognosis):
Diabetic nephropathy is a progressive disorder. Uremia and complications of chronic renal failure occur earlier and progress more rapidly than with glomerular disorders in nondiabetics.

Complications of dialysis or transplantation are more common with diabetic nephropathy, with death occurring from complications of dialysis or transplantation twice as often as in non-diabetics who require these treatments.
Complications:
Calling your health care provider:
Call your health care provider if known diabetic, and routine urinalysis shows protein.

Call your health care provider if symptoms indicate diabetic nephropathy, or if new symptoms develop, including decreased or no urine output.
Prevention:
Blood-glucose levels should be controlled as closely as possible in people with diabetes. Control of blood pressure is even more important than control of blood-sugar.

Review Date: 12/2/2001
Reviewed By: Andrew Koren, M.D., Department of Nephrology, NYU-Mount Sinai Medical Center, New York, NY. Review provided by VeriMed Healthcare Network.
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