Nephropathy

Nephropathy is a broad term for kidney disease or damage that can lead to serious health problems. While it affects millions of people worldwide, early detection and proper management can help slow its progression and protect your overall health.

Table of contents

• What is nephropathy?
• Types of nephropathy
• Diabetic nephropathy
• Who is at risk?
• Signs and symptoms
• Stages of kidney disease
• How is nephropathy diagnosed?
• Treatment and management
• Lifestyle changes and self-care
• Preventing nephropathy

What is nephropathy?

Nephropathy is a broad medical term used to describe disease or damage to the kidneys, which can eventually result in kidney failure^[2]. Your kidneys perform vital functions in your body. They filter waste products from your blood, regulate water balance, and help control acid-base balance^[2]. When your kidneys are damaged, they lose their ability to filter out waste products properly, which can lead to serious health problems.

Nephropathy is considered a progressive illness, meaning that as your kidneys become less effective over time, your condition can worsen if left untreated^[2]. This is why receiving proper diagnosis and treatment as early as possible is crucial for managing the disease and protecting your kidney function.

• Kidneys
• Nephrons
• Glomeruli
• Blood vessels

Types of nephropathy

There are several different types of nephropathy, each with its own causes and characteristics. Understanding the type of kidney disease you have helps your healthcare team provide the most appropriate treatment.

The most common types include diabetic nephropathy, which affects people with diabetes, and IgA nephropathy, which involves deposits of antibodies in the kidneys. Other forms include analgesic nephropathy caused by certain pain medications, and various types that result from immune system disorders^[2].

Diabetic nephropathy

Diabetic nephropathy, also called diabetic kidney disease, is a serious complication that can develop in people with both type 1 and type 2 diabetes^[1]. In the United States, about 1 in 3 people living with diabetes have diabetic nephropathy^[1]. It is the leading cause of end-stage renal disease, which is a life-threatening condition where the kidneys stop working^[3].

Diabetic nephropathy is considered a major complication of diabetes that affects approximately one-third of all diabetic patients^[2]. It affects the kidneys’ normal work of removing waste products and extra fluid from the body^[1]. When you have diabetes, your body can’t properly process blood sugar (glucose) from the foods and drinks you consume. Extra glucose in your bloodstream may damage tiny blood vessels in the kidneys called glomeruli, which act as filters^[5].

The condition usually begins with albuminuria, which means protein appears in the urine, along with changes in how the kidneys filter blood. In the early stage, it often shows up with increased filtering by the kidneys and kidney enlargement^[2]. Over time, if not properly managed, diabetic nephropathy can lead to a progressive decline in kidney function.

The primary features of diabetic kidney disease include enlargement of the filtering units in the kidneys, thickening of the membranes that help filter blood, and accumulation of extra material in the kidney tissue^[3]. These changes gradually reduce the kidneys’ ability to work properly.

IgA nephropathy

Since it was first described in 1968, immunoglobulin A (IgA) nephropathy has remained the most common form of primary glomerulonephritis that can lead to chronic kidney disease^[2]. This condition is very commonly observed in Southern Europe, Australia, and Asia, while in Northern climates of the western world, the incidence is approximately 5-10% of all biopsies for glomerulonephritis^[2].

The diagnostic hallmark of IgA nephropathy is the deposit of IgA antibodies in the glomeruli, either alone or together with other antibodies. The condition involves activation of the body’s immune response and the formation of immune complexes, which play a significant role in how severe the disease becomes^[2]. Young males with visible blood in their urine following an upper respiratory tract infection are highly suspicious for IgA nephropathy^[2].

Who is at risk?

Anyone with type 1 or type 2 diabetes can develop diabetes-related nephropathy^[5]. However, certain factors put you at greater risk. You’re more likely to develop kidney disease if you have diabetes, high blood pressure, heart disease, or a family history of kidney failure^[3][16].

Some racial and ethnic groups face higher risks. People who are Black, Native American, Alaska Native, First Nations, Polynesian, or Maori have a greater chance of developing diabetes-related nephropathy^[5]. About 40% of people who have diabetes develop diabetes-related nephropathy, making it the most common cause of end-stage kidney disease in the world^[5].

Additional risk factors include a family history of kidney disease, using tobacco products, having high blood sugar levels (hyperglycemia), and high cholesterol levels (hyperlipidemia)^[5].

Signs and symptoms

In the early stages of diabetic nephropathy and other forms of kidney disease, there might not be any symptoms at all^[1]. This is why regular testing is so important for people at risk. Diabetes-related nephropathy symptoms usually don’t appear until the disease has affected at least 80% to 90% of your kidneys^[5].

When symptoms do develop, they may include:

• Swelling in your face, hands, and feet, called edema^[5]
• Nausea and vomiting^[5]
• Tiredness or fatigue^[5]
• Shortness of breath, also called dyspnea^[5]
• Loss of appetite^[5]

Early kidney disease may not have any symptoms, so getting tested may be the only way to know your kidneys are healthy^[16]. If you develop a urinary tract infection (UTI), you should see a healthcare provider right away, as UTIs can cause kidney damage if left untreated^[16].

Stages of kidney disease

Kidney disease, including nephropathy, progresses through five stages based on how well your kidneys are filtering blood. This is measured using your estimated glomerular filtration rate (eGFR), which is a calculation of how efficiently your kidneys filter substances^[5]. A normal eGFR is about 100, while the lowest eGFR is 0, which means there is no remaining kidney function^[5].

The five stages are:

• Stage I: Your GFR is 90 or higher. At this stage, your kidneys have mild damage but still function normally^[5].
• 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^[5].
• 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^[5].
• Stage IV: Your GFR may be as low as 15 or as high as 29. You have severe loss of kidney function^[5].
• Stage V: Your GFR is below 15. Your kidneys are nearing or at complete failure^[5].

How is nephropathy diagnosed?

Diabetic nephropathy is usually diagnosed during regular testing that’s part of managing diabetes^[6]. If you have type 2 diabetes or have had type 1 diabetes for more than five years, you should get tested every year^[6].

Routine screening tests may include:

Urinary albumin test: This test can detect a blood protein called albumin in urine. Normally, the kidneys don’t filter albumin out of the blood, so too much albumin in your urine can mean that the kidneys aren’t working well^[6].

Albumin/creatinine ratio: Creatinine is a chemical waste product that healthy kidneys filter out of the blood. This test measures how much albumin compared to creatinine is in a urine sample and shows how well the kidneys are working^[6].

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^[6].

Other diagnostic tests may include imaging tests such as X-rays and ultrasounds to show the makeup and size of the kidneys. CT and MRI scans can show how well blood is moving within the kidneys. In some cases, a kidney biopsy may be needed, which involves taking a small sample of kidney tissue to be studied in a lab^[6].

Screening for early kidney disease is best done with annual spot urine albumin/creatinine ratio testing, and diagnosis is confirmed by repeated elevation in urinary albumin excretion^[8].

Treatment and management

There’s no cure for chronic kidney disease, but treatment can help relieve symptoms and stop it from getting worse^[10]. Your treatment will depend on the stage of your kidney disease. The best way to prevent or delay diabetic nephropathy is by living a healthy lifestyle and keeping diabetes and high blood pressure managed^[1]. Early treatment may prevent this condition or slow it and lower the chance of complications^[1].

Managing blood pressure

Good control of blood pressure is vital to protect the kidneys. People with kidney disease should usually aim to get their blood pressure down to below 140/90 mmHg, but you should aim to get it down to below 130/80 mmHg if you also have diabetes^[10]. Blood pressure should be monitored at every clinical visit and maintained at less than 140/90 mm Hg to prevent changes in the small blood vessels^[8].

There are many types of blood pressure medicines. Medicines called angiotensin converting enzyme (ACE) inhibitors are often used. Examples include ramipril, enalapril, and lisinopril^[10]. If the side effects of ACE inhibitors are troublesome, you can be given a medicine called an angiotensin-II receptor blocker (ARB) instead^[10]. Both ACE inhibitors and ARBs prevent progression of kidney disease and may decrease albuminuria^[8].

Managing blood sugar

If you have diabetes, controlling your blood sugar can help slow the progression of kidney disease^[9]. In people with either type 1 or type 2 diabetes mellitus, high blood sugar has been shown to be a major factor in the progression of diabetic nephropathy^[11]. Intensive therapy can partially reverse some kidney changes, delay the development of protein in the urine, and stabilize kidney function^[11].

Several new medication classes have improved outcomes for patients with diabetes. In adults with diabetes, metformin should be used as first-line therapy for glucose management because it is associated with blood sugar reduction, decreased risk of kidney failure, and decreased mortality^[8]. For patients with kidney disease, GLP-1 receptor agonists or SGLT-2 inhibitors should be considered as second-line therapy to reduce progression of kidney disease^[8].

Managing cholesterol

People with chronic kidney disease have a higher risk of cardiovascular disease, including heart attack and stroke^[10]. You may be prescribed medicines called statins to reduce your risk of developing cardiovascular disease. Examples include atorvastatin and simvastatin^[10]. Statin therapy should be considered for all patients with diabetic kidney disease^[8].

Additional medications

If you also have type 2 diabetes or a high albumin to creatinine ratio, you may be offered a type of medicine called an SGLT2 inhibitor, such as dapagliflozin, as well as medicines for high blood pressure. Dapagliflozin helps to lower your blood sugar and can reduce damage to your kidneys^[10].

You may also be given an additional medicine called finerenone to take with dapagliflozin. Finerenone works by blocking the action of certain hormones that can damage your kidneys^[10].

It’s very important that you take any prescribed medicine, even if you don’t feel unwell. Some medicines are designed to prevent serious problems from happening in the future^[17].

Advanced kidney disease

In advanced cases of kidney disease (stage 5), treatment options include dialysis or a kidney transplant^[1]. Dialysis is a treatment to replicate some of the kidney’s functions. There are two different types: hemodialysis, which cleans the blood through a machine at a dialysis center, and peritoneal dialysis, where fluid is put into your abdomen to remove toxins^[6][13].

Lifestyle changes and self-care

Taking an active role in managing chronic kidney disease will help you feel better and improve your overall well-being^[18]. While it’s not possible to reverse kidney damage that has already happened, chronic kidney disease will not necessarily get worse. The condition only reaches an advanced stage in a small proportion of people^[17].

Healthy eating

If you have chronic kidney disease, you may not need a special diet, but a healthy, balanced diet can help improve your general health and reduce your risk of developing further problems^[17]. Choose foods that are healthy for your heart and your entire body: fresh fruits, fresh or frozen vegetables, whole grains, and low-fat or fat-free dairy products^[16].

You should limit salt, as eating healthy meals and cutting back on salt and added sugars is important. Aim for less than 2,300 milligrams of sodium each day^[16]. You should restrict your salt intake to less than 6g a day, which is around 1 teaspoon^[17]. Reducing dietary salt intake may help slow progression of diabetic kidney disease. Get creative with herbs, spices, mustard, and flavored vinegars in your favorite recipes^[18].

If blood tests show you have high levels of potassium and phosphate in your blood, you may be referred to a dietitian who will give you advice about changes you can make to your diet^[17]. Some foods that work well for both diabetes and chronic kidney disease include berries, grapes, cherries, apples, plums, cauliflower, onions, eggplant, turnips, lean meats, fish, eggs, unsalted seafood, white bread, bagels, unsalted crackers, pasta, water, clear diet sodas, and unsweetened tea^[18].

Physical activity

Regular physical activity can help improve your general health. Don’t be scared to exercise—it is good for anyone with kidney disease, however severe^[17]. Not only will it boost your energy, help you sleep, strengthen your bones, and ward off depression, it may also reduce your risk of problems such as heart disease^[17].

Physical activity is good for anyone with kidney disease, whether you have mild, moderate, or severe chronic kidney disease. It can boost your energy, help you sleep, strengthen your bones, and help prevent depression. It may also reduce your risk of problems such as heart disease^[18]. If you have mild to moderate kidney disease, you should be able to be active as often as someone with healthy kidneys^[18]. Aim to do at least 150 minutes of exercise a week^[17].

Quit smoking and limit alcohol

If you smoke, stopping smoking can improve your overall health and reduce your risk of many other health problems^[17]. Smoking can make kidney disease worse and interfere with medicine that lowers blood pressure^[8]. Tobacco cessation reduces the risk of diabetic kidney disease^[8].

You may still be able to drink alcohol if you have kidney disease, but it’s advisable not to exceed the recommended limit of more than 14 alcohol units a week^[17]. Alcohol can increase your risk of high blood pressure^[18]. Manage your alcohol intake so you drink no more than the recommended limit of 14 units of alcohol a week, and lose weight if you’re overweight or obese^[10].

Vaccinations

Kidney disease can put a significant strain on your body and make you more vulnerable to infections. Everyone with the condition is encouraged to have the annual flu jab and the one-off pneumococcal vaccination^[17]. Get your annual flu shot to protect your health^[18].

Medication safety

Check with your care team if you plan to take any painkillers or nutritional supplements. These can sometimes affect your kidneys or interfere with your medicine^[18]. Avoid over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, except when advised to by a medical professional, as these medicines can harm your kidneys if you have kidney disease^[10].

Preventing nephropathy

You can protect your kidneys by preventing or managing health conditions that cause kidney damage, such as diabetes and high blood pressure^[16]. Prevention of diabetes in the general population is the most effective means of minimizing the impact of diabetic kidney disease^[8].

The steps described for healthy living may help keep your whole body healthy, including your kidneys. During your next medical visit, you may want to ask your healthcare provider about your kidney health. Early kidney disease may not have any symptoms, so getting tested may be the only way to know your kidneys are healthy. Your healthcare provider will help decide how often you should be tested^[16].

Make healthy food choices, cook with a mix of spices instead of salt, choose veggie toppings for your meals, try baking or broiling meat instead of frying, eat foods made from whole grains every day, and read food labels to choose foods low in saturated fats, trans fats, cholesterol, salt, and added sugars^[16].

If you have diabetes, stay in your target blood sugar range as much as possible. Keep your blood pressure below 140/90 mm Hg or the target set by your doctor^[18]. Given the complexity of the disease and the risk of poor outcomes, patients who progress to stage 3 chronic kidney disease or beyond may benefit from referral to nephrology specialists^[8].