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Diabetic Nephropathy

Practice Essentials

Diabetic nephropathy is a clinical syndrome characterized by the following
:

Persistent albuminuria (>300 mg/d or >200 μg/min) that is confirmed on at least 2 occasions 3-6 months apart

Progressive decline in the glomerular filtration rate (GFR)

Elevated arterial blood pressure (see Workup)

Proteinuria was first recognized in diabetes mellitus in the late 18th century. In the 1930s, Kimmelstiel and Wilson described the classic lesions of nodular glomerulosclerosis in diabetes associated with proteinuria and hypertension. (See Pathophysiology.)

By the 1950s, kidney disease was clearly recognized as a common complication of diabetes, with as many as 50% of patients with diabetes of more than 20 years having this complication. (See Epidemiology.)

Currently, diabetic nephropathy is the leading cause of chronic kidney disease in the United States and other Western societies. It is also one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes. Diabetes is responsible for 30-40% of all end-stage renal disease (ESRD) cases in the United States. (See Prognosis.)

Generally, diabetic nephropathy is considered after a routine urinalysis and screening for microalbuminuria in the setting of diabetes. Patients may have physical findings associated with long-standing diabetes mellitus. (See Clinical Presentation.)

Good evidence suggests that early treatment delays or prevents the onset of diabetic nephropathy or diabetic kidney disease. This has consistently been shown in both type 1 and type 2 diabetes mellitus.
(See Treatment and Management).

Regular outpatient follow-up is key in managing diabetic nephropathy successfully. (See Long-term Monitoring.)

Recently, attention has been called to atypical presentations of diabetic nephropathy with dissociation of proteinuria from reduced kidney function. Also noted is that microalbuminuria is not always predictive of diabetic nephropathy.
Nevertheless, a majority of the cases of diabetic nephropathy present with proteinuria, which progressively gets worse as the disease progresses, and is almost uniformly associated with hypertension.

Go to Diabetes Mellitus, Type 1 and Diabetes Mellitus, Type 2 for more complete information on these topics.

Signs and symptoms of diabetic nephropathy

Diabetic nephropathy should be considered in patients who have diabetes mellitus (DM) and a history of one or more of the following:

Passing of foamy urine

Otherwise unexplained proteinuria

Diabetic retinopathy

Fatigue and foot edema secondary to hypoalbuminemia (if nephrotic syndrome is present)

Other associated disorders such as peripheral vascular occlusive disease, hypertension, or coronary artery disease

Workup in diabetic nephropathy

Diabetic nephropathy is characterized by the following:

Persistent albuminuria (>300 mg/d or >200 μg/min) that is confirmed on at least two occasions 3-6 months apart

A relentless decline in the glomerular filtration rate (GFR)

Elevated arterial blood pressure

A 24-hour urinalysis for urea, creatinine, and protein is extremely useful in quantifying protein losses and estimating the GFR.

Blood tests, including calculation of GFR (by various formulas, such as the modification of diet in renal disease [MDRD] formula), are helpful in monitoring for the progression of kidney disease and in assessing its stage.

Renal ultrasonography is performed to observe for kidney size, which is usually normal to increased in the initial stages and, later, decreased or shrunken with chronic renal disease. Rule out obstruction. Perform echogenicity studies for chronic renal disease.

Management of diabetic nephropathy

Several issues are key in the medical care of patients with diabetic nephropathy.
These include glycemic control, management of hypertension, and reducing dietary salt intake and phosphorus and potassium restriction in advanced cases.

Agents for glycemic control in patients with diabetes who have kidney disease include the following:

Dipeptidyl peptidase inhibitors

Alpha-glucosidase inhibitors

Sodium-glucose cotransporter 2 (SGLT2) inhibitors

Glucagonlike peptide-1 (GLP-1) receptor agonists or incretin mimetics

Amylin analogs

Nonsteroidal, selective mineralocorticoid receptor (MR) antagonists

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