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Proteinuria and Diabetes byShu Golda
Diabetic kidney disease is one of the chronic complications of diabetes. Kidney disease and cardiovascular disease are closely related; diabetic kidney disease can increase mortality from cardiovascular diseases (1). Proteinuria is one of several markers of kidney damage in diabetes. In proteinuria, urine contains different molecular weight proteins including albumin (albuminuria). It is defined by increased excretion of albumin in urine when other renal diseases are absent (2). This condition can be a sign of kidney damage. Proteins ¾ which help build muscle and bone, regulate the amount of fluid in the blood, combat infection, and repair tissue ¾ should remain in the blood. It is not healthy for proteins to be found in the urine.

Proteinuria in diabetes usually results either from long term hyperglycemia (high blood sugar levels) or hypertension (high blood pressure) (3)

How do proteins get into urine? 

Protein gets into the urine if the kidneys are not functioning properly. The glomeruli which are tiny loops of capillaries (blood vessels) in the kidneys, filter waste products and excess water from the blood. The glomeruli allow smaller molecules-waste and water to be filtered into the urine and not larger proteins and blood cells. If smaller proteins sneak through the glomeruli, tubules (long thin, hollow tubes in the kidneys) recapture those proteins and keep them in the body.

However, if the glomeruli or tubules are damaged, if there is a problem with the reabsorption process of the proteins, or if there is an excessive protein load, the proteins will flow into the urine.

What is proteinuria?

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When the kidneys are working correctly they filter waste products out of the blood but keep in important elements including albumin. Albumin is the protein that helps to prevent water from leaking out of the blood into other tissues.

Prolonged hyperglycemia can cause kidney damage, allowing the loss of albumin from blood to the urine. Proteinuria is therefore a sign of kidney damage in diabetes.

Signs and symptoms of proteinuria 

The signs of proteinuria only become noticeable once the kidneys have become very damaged and levels of protein in the urine are high. When this happens, symptoms such as swelling of the ankles, hands, tummy, or face may present.

Screening and diagnosis of albuminuria.

Since the symptoms only occur at a later stage of kidney damage, diabetics must be screened for kidney disease at least once a year.

The screening involves providing a sample of urine which will be tested by the health team for any abnormal levels of protein. This is done by comparing the ratio of albumin to creatinine.

Urine albumin excretion is generally evaluated as an albumin/creatinine ratio (ACR) in either milligrams per millimoles or milligrams per gram when spot. The sample should preferably be early morning urine.

Healthy albumin to creatinine ratio is defined as:

  • Men: less than or equal to 2.5mg/mmol.
  • Women: less than or equal to 3.5mg/mol.

Causes of Proteinuria.

The main cause of proteinuria in diabetes patients is prolonged hyperglycemia. High blood pressure can also lead to the development of kidney damage.

Pre-eclampsia, a condition that can affect pregnant women, includes very high blood pressure and is another potential cause of protein in the urine.

One of such proteins found in urine is albumin. Between 4% and 15% of adults with diabetes have small amounts of albumin leaking into their urine, a condition known as microalbuminuria (2). Microalbuminuria can progress to kidney disease hence; early detection is important. Microalbuminuria cannot be detected by standard urine tests; it can only be detected by special tests that became available within the past 20 years.

If the injury to the blood filters gets worse, larger amounts of albumin may begin to leak into the urine. This stage is called clinical albuminuria or clinical nephropathy. Because so much albumin is lost in the urine, the level of albumin in the blood falls below the normal range. Albumin is needed for blood to hold water inside the arteries and capillaries. When there’s not enough albumin, water can accumulate in the tissues, causing swelling in the legs (edema), chest, and abdomen. People with clinical nephropathy may notice that their shoes and clothes no longer fit. Carrying extra water weight can cause fatigue and shortness of breath.

Treatment for Proteinuria.

The primary treatment for proteinuria will be to control both blood pressure and blood glucose levels, which may be achieved through lifestyle changes and could include taking additional medication. Water tablets, a diuretic medication that helps to remove water from the body can be administered if fluids accumulate in the ankles or around the lungs. If the level of kidney damage is severe, kidney dialysis or a kidney transplant might be done.

Risk factors of proteinuria

The following subset of patients are more prone to proteinuria:

  • Genetic predisposition
  • Sustained hyperglycemia and hypertension
  • Smokers
  • Dyslipidemia
  • The type and source of proteins and fats consume

Prevention of proteinuria (albuminuria)

Prevention: normoalbuminuric patients

The primary preventive measure for proteinuria is the treatment of all risk factors such as hyperglycemia, hypertension, dyslipidemia, and smoking. Risk factors for cardiovascular diseases should also be targeted.

Intensive blood-glucose control

Blood glucose regulation is primary in the prevention of diabetes complications like kidney disease. At A1c levels <7% there is less risk of diabetic nephropathy in type 1 and type 2 diabetic patients.

Blood pressure control

Hypertension is common in diabetes patients, and control of this high blood pressure can reduce the risk of cardiovascular and microvascular diseases in diabetics. Diabetes patients should target blood pressure 130/80mmHg.

Treatment: micro- and macroalbuminuric patients

The goal of treatment is to prevent the progression from micro- to macroalbuminuria, the decline of renal function in patients with macroalbuminuria, and the occurrence of cardiovascular events (1). Both treatment and prevention have the same strategies, however these strategies are more intense during treatment.

Intensive blood-glucose control

Blood glucose levels can be dropped by using some oral antihyperglycemic drugs such as Rosiglitazone. Metformin should not be used when serum creatinine is >1.5 mg/dl in men and >1.4 mg/dl in women due to the increased risk of lactic acidosis (1). As such, it is preferable to treat. Thus, most type 2 diabetic patients with diabetic nephropathy with insulin.

Intensive blood pressure treatment and renin-angiotensin system blockade

Regardless of the agent used, treatment of hypertension has been shown to have a beneficial consequence on diabetes patients with albuminuria.

Dietary intervention

Reducing the intake of proteins, cholesterol, and saturated fats can reduce the chances of microalbuminuria from developing to albuminuria. An example of this dietary change can be replacing red meat with skinless chicken. Chicken contains a lower amount of saturated fat and a higher proportion of polyunsaturated fatty acids than red meat.

Dyslipidemia

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The target level for Low-Density Lipoprotein cholesterol is <100 mg/dl for diabetic patients in general and <70 mg/dl for diabetic patients with cardiovascular disease

Anemia

Anemia in diabetic patients with kidney disease is related to erythropoietin deficiency, and may occur before advanced kidney failure (serum creatinine <1.8 mg/dl). This anemia can also be a contributing factor to kidney failure. Begin erythropoietin treatment when hemoglobin levels are <11 g/dl. Target Hb levels should be 12–13 g/dl.

In diabetic patients with albuminuria and kidney disease, reducing albumin levels may reduce the disease outcome and kidney disease progression. Albuminuria is not at the endpoint for cardiovascular diseases but it is more likely to show the disease manifestation. Thus, albuminuria is useful in the identification of patients at risk of cardiovascular diseases.