Diabetic Nephropathy

Diabetic nephropathy is a serious kidney disease caused by diabetes that affects millions of people worldwide. It develops slowly over many years and can eventually lead to kidney failure if not properly managed. Understanding this condition and taking early action can help protect your kidneys and improve your overall health.

Table of contents

• What is diabetic nephropathy?
• Who is affected by diabetic nephropathy?
• How does diabetes damage the kidneys?
• Stages of diabetic nephropathy
• Symptoms
• How is it diagnosed?
• Treatment and management
• Prevention
• Outlook and prognosis

What is diabetic nephropathy?

Diabetic nephropathy is a serious complication of both type 1 and type 2 diabetes. It is also called diabetic kidney disease (DKD)^[1]. This condition affects the kidneys’ normal work of removing waste products and extra fluid from the body^[1].

Your kidneys contain more than a million tiny filtering units called nephrons. Each nephron contains groups of tiny blood vessels called glomeruli, which perform the first step in filtering your blood. When you have diabetes, extra glucose (blood sugar) in your bloodstream can damage these glomerular membranes and other parts of the nephron^[3].

Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in developed countries, including the United States^[2]. In the United States, about 1 in 3 people living with diabetes have diabetic nephropathy^[1].

• Kidneys
• Glomeruli
• Nephrons
• Blood vessels

Who is affected by diabetic nephropathy?

Anyone with type 1 or type 2 diabetes can develop diabetic nephropathy^[3]. Globally, approximately 20% of the 400 million individuals with diabetes mellitus have diabetic kidney disease^[11]. About 40% of people who have diabetes develop diabetes-related nephropathy^[3].

You are at greater risk of developing diabetic nephropathy if you are Black, Native American, Alaska Native, First Nations, Polynesian, or Maori^[3].

Other risk factors include^[3]:

• A family history of kidney disease
• High blood pressure
• Using tobacco products
• Hyperglycemia (high blood sugar)
• Hyperlipidemia (high cholesterol)
• Male sex
• Age at diagnosis
• Level of formal education

How does diabetes damage the kidneys?

High blood sugar linked to diabetes damages the kidney in several different ways. Mainly, it damages the blood vessels that filter the blood to make urine. People with diabetes also often develop high blood pressure, which can also damage your kidneys^[7].

The primary features of diabetic kidney disease include glomerular hypertrophy (enlargement of the filtering units), glomerular basement membrane thickening, changes in the structures that filter blood, and expansion of the tissue that supports the glomeruli^[2].

Diabetic nephropathy has multiple mechanisms involving tiny blood vessel changes and larger blood vessel changes. These changes lead to protein in the urine (albuminuria) and decreased filtering of waste from the blood^[11].

Stages of diabetic nephropathy

Diabetic nephropathy progresses through stages according to your estimated glomerular filtration rate (eGFR). Your eGFR is a calculation of how efficiently your kidneys filter substances. A normal eGFR is about 100. The lowest eGFR is 0, which means there is no remaining kidney function^[3].

The stages of kidney disease include^[3]:

• Stage I: Your GFR is 90 or higher. At this stage, your kidneys have mild damage but still function normally.
• Stage II: Your GFR may be as low as 60 or as high as 89. You have more damage to your kidneys than in stage I, but they still function well.
• Stage III: Your GFR may be as low as 30 or as high as 59. You may have mild or severe loss of kidney function.
• Stage IV: Your GFR may be as low as 15 or as high as 29. You have severe loss of kidney function.
• Stage V: Your GFR is below 15. Your kidneys are nearing or at complete failure.

Going from one stage to the next can take many years. It is rare for kidney failure to happen in the first 10 years of diabetes. Kidney failure often happens 15 to 25 years after the first symptoms of diabetes^[7].

Symptoms

In the early stages of diabetic nephropathy, there might not be symptoms^[1]. Until diabetic kidney disease is severe, most people with it don’t have symptoms. Having your kidney function checked by a simple blood and urine test is the only way to know if there are problems^[7].

Diabetes-related nephropathy symptoms usually don’t appear until it has affected at least 80% to 90% of your kidneys^[3]. These symptoms include:

• Swelling in your face, hands and feet (edema)
• Nausea and vomiting
• Tiredness or fatigue
• Dyspnea (shortness of breath)
• Loss of appetite
• Weight loss
• Weakness
• Trouble sleeping
• Foamy urine
• Peeing more often

As your kidneys become less able to do their job, you may have higher blood pressure, higher cholesterol and triglyceride levels, and lose more protein in your urine^[7].

How is it diagnosed?

Diabetic nephropathy usually is diagnosed during the regular testing that’s part of managing diabetes. Get tested every year if you have type 2 diabetes or have had type 1 diabetes for more than five years^[9].

If you have diabetes, it’s important to be checked regularly for kidney disease. Individuals with type 2 diabetes mellitus should be screened for albuminuria at the time of diagnosis and annually thereafter^[11].

Routine screening tests may include^[9]:

• Urinary albumin test: This test can detect a blood protein called albumin in urine. Typically, the kidneys don’t filter albumin out of the blood. Too much albumin in your urine can mean that the kidneys aren’t working well.
• Albumin/creatinine ratio: Creatinine is a chemical waste product that healthy kidneys filter out of the blood. The albumin/creatinine ratio measures how much albumin compared to creatinine is in a urine sample. It shows how well the kidneys are working.
• Glomerular filtration rate (GFR): The measure of creatinine in a blood sample may be used to see how quickly the kidneys filter blood. A low rate means the kidneys aren’t working well.

A routine urine dipstick test doesn’t pick up albumin in the urine until you are leaking more than 300 to 500 mg a day. This is now called severely increased albuminuria. For amounts less than 300 mg a day, the term is moderately increased albuminuria. This change in wording shows that any amount of protein in the urine is abnormal^[7].

Other diagnostic tests may include imaging tests such as X-rays and ultrasound to show the makeup and size of the kidneys, or a kidney biopsy to take a sample of kidney tissue to be studied in a lab^[9].

Treatment and management

The best way to prevent or delay diabetic nephropathy is by living a healthy lifestyle and keeping diabetes and high blood pressure managed^[1]. Good evidence suggests that early treatment delays or prevents the onset of diabetic nephropathy^[4].

Treatment will depend on your symptoms, age, and general health. It will also depend on how severe the condition is^[7]. Treatment may include:

• Blood pressure management: The main treatment is medicine to lower your blood pressure and prevent or slow the damage to your kidneys. Medicines include angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs)^[7]. Blood pressure should be monitored at every clinical visit and maintained at less than 140/90 mm Hg to prevent microvascular changes^[11].
• Blood sugar control: Strict checking and controlling of blood sugar levels, often with medicine and insulin injections^[7]. Keep your blood sugar levels within your target range^[7].
• New diabetes medications: Several new medication classes have improved the prognosis for patients with diabetes mellitus. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists should be considered as second-line therapy for patients with diabetic kidney disease to reduce progression^[11]. In 2019, SGLT2 inhibitors showed effectiveness against diabetic kidney disease^[12].
• Cholesterol management: Statin therapy should be considered for all patients with diabetic kidney disease^[11].
• Dietary modifications: Following the correct diet, including possibly being advised to watch how much protein you eat^[7]. Patients with diabetic kidney disease should eat a protein-restricted diet (0.8 g per kg per day)^[11]. Limit your salt to help keep high blood pressure from getting worse^[7]. Reducing dietary salt intake may help slow progression of diabetic kidney disease^[13].
• Exercise: Engage in regular physical activity^[7].
• Avoiding harmful substances: Tobacco cessation reduces the risk of diabetic kidney disease^[11]. Not taking other medicines that harm the kidneys, including some pain medicines^[7].

If your diabetic kidney disease becomes more severe, you will need a referral to a kidney specialist (nephrologist). Patients who progress to stage 3 diabetic kidney disease or beyond may benefit from referral to nephrology subspecialists^[11]. For kidney failure, you will need dialysis to cleanse the blood, or a kidney transplant^[7].

Prevention

You can protect your kidneys by preventing or managing health conditions that cause kidney damage, such as diabetes and high blood pressure^[22]. Prevention of diabetes in the general population is the most effective means of minimizing the impact of diabetic kidney disease^[11].

Steps that may help keep your whole body healthy, including your kidneys, include^[22]:

• Make healthy food choices: Choose foods that are healthy for your heart and your entire body, such as fresh fruits, fresh or frozen vegetables, whole grains, and low-fat or fat-free dairy products. Eat healthy meals, and cut back on salt and added sugars. Aim for less than 2,300 milligrams of sodium each day.
• Keep your blood sugar within target range: Work with your doctor to maintain optimal blood glucose control^[7].
• Control your blood pressure: Managing blood pressure is crucial for preventing diabetic kidney disease^[7].
• Maintain a healthy weight: Maintaining a healthy weight can have a positive impact on overall kidney health^[3].
• Exercise regularly: Engaging in regular physical activity helps control risk factors^[3].
• Avoid smoking: Avoiding smoking can have a positive impact on kidney health^[3].

Early kidney disease may not have any symptoms, so getting tested may be the only way to know your kidneys are healthy. During your next medical visit, you may want to ask your health care provider about your kidney health^[22].

Outlook and prognosis

Diabetic nephropathy is a serious condition. It can lead to kidney failure, which is a life-threatening condition. Kidney failure can be fatal^[3].

Diabetic kidney disease is associated with increased risks of morbidity and mortality and is the leading cause of end-stage renal disease in the United States^[11]. Rates of cardiovascular morbidity and mortality rise dramatically with the progression of renal disease. For patients who develop severely increased albuminuria, in any given year the risk of mortality (4.6%) is higher than the risk of progression to end-stage renal disease (2.3%)^[11].

However, with early detection and proper treatment, the progression of diabetic nephropathy can be slowed or delayed. Over years, diabetic nephropathy slowly damages the kidneys’ filtering system. Early treatment may prevent this condition or slow it and lower the chance of complications^[1].

If you have had diabetes for more than 25 years without any signs of kidney failure, your risk of having it decreases^[7].

Treatment options for kidney failure are dialysis or a kidney transplant^[1]. Several new medication classes have improved the prognosis for patients with diabetes mellitus^[2].