Nephrotic Syndrome

Nephrotic Syndrome What is nephrotic syndrome? Nephrotic syndrome is a sign that your kidneys are not working right. You have nephrotic syndrome if you have high levels of protein in your urine, low levels of protein in the blood, and high cholesterol. Nephrotic syndrome is not a disease. It is a warning that something is damaging your kidneys. Without treatment, that problem could cause kidney failure, so it’s important to get treatment right away.

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Nephrotic syndrome is caused by damage to the tiny blood vessels in the kidney that filter waste and excess water from the blood. Many conditions and diseases can cause nephrotic syndrome, including:

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Nephrotic syndrome can occur at any age, but it is most common in children between the ages of 18 months and 8 years. What causes nephrotic syndrome?

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There are tiny blood vessels in the kidneys that filter waste and extra water from the blood. When these filters are damaged, you get nephrotic syndrome. Protein helps move water from the tissues into the blood. Healthy kidneys keep the right amount of protein in the blood. Damaged kidneys let protein slip from the blood into the urine. Without enough protein in the blood, fluid builds up in the tissues. This can cause swelling. Many things can cause this blood vessel damage, including diabetes, lupus, infection, certain cancers, and some medicines. Sometimes doctors don't know what causes it. A type of kidney disease called minimal change disease (also called nil disease) causes most of the cases of nephrotic syndrome in children. Doctors don't know what causes minimal change disease.

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What are the symptoms?

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The most common early symptom of nephrotic syndrome, in both children and adults, is swelling in the tissues around the eyes or in the feet or ankles. They may also have swelling in the lungs that can make it hard to breathe.

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But many people who have nephrotic syndrome don't have symptoms. How is nephrotic syndrome diagnosed? Doctors diagnose nephrotic syndrome using blood and urine tests. You may have other tests to see what is causing nephrotic syndrome. Adults may also have a kidney biopsy, in which the doctor takes a sample of tissue to test for cancer.

With treatment, young children usually get better and have no lasting problems. Often treatment is not as successful in older children and adults. If the kidney damage is not stopped, it can lead to chronic kidney disease. *********************** Learning about nephrotic syndrome:

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What causes it?

Minimal change disease (also called nil disease), a type of kidney disease. The cause of minimal change disease is unknown, but it causes most of the cases of nephrotic syndrome in children.1 Membranous glomerulopathy and focal segmental glomerulosclerosis, which are two other diseases of the kidney. Both of these diseases affect the glomeruli. The glomeruli help filter waste out of your blood. In focal segmental glomerulosclerosis, some of the parts of the glomeruli have scar tissue. This can affect how they filter the blood. In membranous glomerulopathy, the tissue wall (membrane) that separates blood and urine and acts as a filter in your kidney becomes thickened and damaged. Diabetes and lupus. Diabetes is the most common cause of nephrotic syndrome in adults in the United States.2 Infections, such as HIV, hepatitis B, hepatitis C, syphilis, malaria, tuberculosis, or post-streptococcal glomerulonephritis. Cancer, such as breast cancer, lung cancer, Hodgkin's lymphoma, or multiple myeloma. Medicines, such as nonsteroidal anti-inflammatory drugs, penicillamine, gold therapy, or captopril. Illegal drugs, such as heroin. Conditions such as preeclampsia, chronic graft rejection following an organ transplant, and allergic reactions to bee stings. Unknown (idiopathic) factors.

Symptoms Many people who have nephrotic syndrome do not have any noticeable physical symptoms. When symptoms are present, they can include:

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How is it treated? Treatment focuses on reversing, slowing, or preventing further kidney damage. The treatment you need depends on whether you are an adult or a child and what health problem caused nephrotic syndrome. You may take medicine, and your doctor may suggest a diet that is low in salt and protein.

What are the symptoms? What increases my risk for nephrotic syndrome?

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Swelling in the tissues around the eyes (periorbital edema) or in the feet or ankles (peripheral edema). This is the most common early symptom of nephrotic syndrome in both children and adults. Shortness of breath caused by fluid buildup in the lungs (pulmonary edema). o Adults older than 65 may be misdiagnosed with heart failure. o Children are often thought to have allergies. Dry skin. Swelling of the scrotum (scrotal edema), which may cause a cord in the testicles to twist (testicular torsion).

Signs of nephrotic syndrome in blood and urine tests can include:

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Low protein (albumin) in the blood. High cholesterol and triglyceride levels. Low blood levels of iron and vitamin D. Protein in the urine (proteinuria).

What Increases Your Risk Diabetes is the most common cause of nephrotic syndrome in adults in the United States. About one-third of children who develop nephrotic syndrome have diabetes.

You also have an increased risk of developing nephrotic syndrome if you have a disease that results in an impaired immune system, such as AIDS or lupus. Nephrotic syndrome is a relatively rare disease that can occur at any age. In the United States, it affects between 2 and 7 people out of 100,000 each year. Children most commonly affected are between the ages of 18 months and 8 years. Boys are affected more often than girls. ******************************************

Being diagnosed:

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Who can diagnose and treat nephrotic syndrome? How will my doctor diagnose nephrotic syndrome? Can it be prevented?

When To Call a Doctor Call 911 or other emergency services if you have nephrotic syndrome and you develop:

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Chest pain. Severe shortness of breath or difficulty breathing. Sudden and severe abdominal or one-sided (flank) pain.

Call your doctor immediately if you have:

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Bloody urine (gross hematuria). Sudden, severe swelling in your legs, and pain when you flex your feet. Swelling of the scrotum. Sudden, severe increase in swelling around the eyes or in the hands, legs, or feet. Sudden weight gain, such as 2 lb (0.9 kg) in 24 hours or 5 lb (2.3 kg) in a week.

In adults, additional testing usually includes:

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Unless nephrotic syndrome is clearly caused by diabetes, a kidney biopsy is usually done to find the cause. Children do not usually have a biopsy. Prevention Avoiding situations or controlling the other diseases that can contribute to kidney disease can sometimes prevent nephrotic syndrome. The earlier a person changes factors that damage the kidneys, the better. You can help prevent kidney damage by:

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If you think your child or you may have nephrotic syndrome, or if your child or you have the condition and the symptoms are getting worse, don't wait to get treatment. Call your doctor right away. Exams and Tests In addition to a medical history and physical exam, other tests to diagnose nephrotic syndrome include:

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A 24-hour urine collection, which measures the total amount of protein in the urine collected over 24 hours. You will be diagnosed with nephrotic syndrome if you have more than 3500 mg of protein in your urine. Urine test for albumin. Lower levels of albumin in the blood can cause fluid to collect in the ankles, lungs, or abdomen. Creatinine and creatinine clearance. Results of these tests give information on how well your kidneys are working. Blood profile tests to measure the amount of protein, cholesterol, and sugar (glucose) in the blood. Kidney ultrasound to look at the kidneys. This exam can rule out other causes of your symptoms.

You may need other tests before treatment for nephrotic syndrome begins, including:

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A test for varicella (chickenpox) antibodies. A bone density scan.

Keeping your blood pressure at less than 125/75 mm Hg with medication, diet, and exercise. For more information, see the topic High Blood Pressure (Hypertension). Keeping strict control over your blood glucose level if you have diabetes. For more information, see the topic Type 1 Diabetes or Type 2 Diabetes. Maintaining healthy levels of fats (lipids), such as cholesterol and triglycerides. For more information, see the topic High Cholesterol. Not smoking or using other tobacco products. For more information, see the topic Quitting Tobacco Use.

If you were diagnosed with nephrotic syndrome in the past:

Watchful Waiting

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Serum protein electrophoresis (SPEP). Antinuclear antibodies (ANA). Antibody tests for systemic lupus erythematosus. C3 and C4 complement, proteins normally found in the blood. Tests for hepatitis B and hepatitis C.

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Avoid dehydration. For more information, see the topic Dehydration. o Promptly treat illnesses that cause dehydration, such as diarrhea, vomiting, or fever. o Prevent dehydration during hot weather and when you exercise. Drink 8 to 10 glasses of fluids (water or rehydration drinks) each day. Drink extra water before, during, and after exercise. Take a container of water or sports drink with you when you exercise, and try to drink at least every 15 to 20 minutes. Use a sports drink if you will be exercising for longer than 1 hour. o Avoid caffeine drinks, such as coffee and colas. They increase urine output, which increases dehydration. o Avoid alcoholic beverages. They increase urine output, which increases dehydration. o Do not take salt tablets. Most people get plenty of salt in their diets. Use a sports drink if you are worried about replacing minerals lost through sweating. Do not use a sports drink if you have heart failure unless you are instructed to do so by your doctor. o Stop working outdoors or exercising at the first sign of dizziness, lightheadedness, or fatigue. o Wear one layer of lightweight, light-colored clothing when you are working or exercising outdoors. Replace sweaty clothing with dry clothing as soon as you can. Avoid medications that may harm the kidney. Avoid X-ray tests that use contrast material. Prevent heart disease. Lifestyle changes—eating a lowfat diet, quitting smoking, and getting regular exercise— can help reduce your overall risk of developing heart disease and stroke. For more information, see the topic Coronary Artery Disease.

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Getting treatment:

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How is nephrotic syndrome treated? Will I need to take medicines? Is surgery used to treat nephrotic syndrome?

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Treatment Overview

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Treatment for nephrotic syndrome depends on the cause and the age of the person who has the condition. Medicines, changes in diet, and care for other conditions, such as diabetes or high blood pressure, are all possible treatments for this syndrome. These treatments may reverse, slow or prevent further kidney damage.

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Most children who have nephrotic syndrome do well with treatment and have a normal life expectancy. Children older than age 12 at the time of diagnosis and adults who also have diabetes or high blood pressure do not respond as well to treatment as do children younger than 12. Doctors define complete recovery as living without symptoms or treatment for more than 2 years.1 Initial treatment Treatment of nephrotic syndrome depends on the cause of the disease and may include:

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Corticosteroids, such as prednisone or prednisolone, to reduce swelling. Diuretics, such as bumetanide (Bumex) or furosemide (Lasix), to reduce fluid buildup in the body (edema) and help with reducing sodium, potassium, and water. Fluid reduction should occur slowly to avoid further kidney damage and low blood pressure. Medications, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), to reduce the amount of protein lost in the urine, lower blood pressure, and slow the progress of the disease. In rare cases, salt-free albumin given through a vein (IV). Albumin helps remove extra fluid from the tissues.

You may need emotional support during treatment for nephrotic syndrome. If you or your child has nephrotic syndrome and you are having a hard time handling treatment or the severity of your child's condition, talking with a doctor or seeking counseling may help. First treatments can last from 6 to 15 weeks, often longer in adults.4 Depending on how severe your symptoms are or whether they return, ongoing treatment may be necessary for months to years, or even the rest of your life. Ongoing treatment Ongoing treatment for nephrotic syndrome and complications of the disease include:

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Daily or alternate-day prednisone, if nephrotic syndrome returns. Cyclophosphamide, cyclosporine, or CellCept, when treatment with corticosteroids is not successful. Steps to lower blood pressure, including medication, a healthier diet, and exercise. Untreated high blood pressure increases your risk for stroke or heart attack. For more information, see the topics High Blood Pressure (Hypertension), Coronary Artery Disease, and Stroke.

Changes in diet to replace nutrients lost through the urine, reduce fluid buildup in the body, and reduce the risk of complications. Some doctors prescribe a diet that limits protein, salt (sodium), and fats but is high in carbohydrates. The amount of protein allowed may vary, depending on your condition. Anticoagulants, such as warfarin (Coumadin) or heparin, to treat blood clots if they form. Early treatment of infections with antibiotics. Vaccinations with a pneumococcal vaccine (What is a PDF document?), such as Pneumovax, to prevent infections; chickenpox (varicella) vaccines; and a yearly flu shot. Vaccination is not recommended until nephrotic syndrome has responded to treatment with corticosteroids.5, 6 Calcium and vitamin D supplements to protect your bones and help prevent osteoporosis during long-term corticosteroid treatment (for example, prednisone).

You can help slow the progression of kidney damage caused by nephrotic syndrome by:

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Keeping blood pressure at less than 125/75 mm Hg with medication, diet, and exercise. For more information, see the topic High Blood Pressure (Hypertension). Keeping strict blood glucose control if you have diabetes. For more information, see the topics Type 1 Diabetes and Type 2 Diabetes. Maintaining healthy levels of fats (lipids), such as cholesterol and triglycerides. For more information, see the topic High Cholesterol. Not smoking or using other tobacco products. For more information, see the topic Quitting Tobacco Use. Avoiding medications that may harm the kidneys. Avoiding X-ray tests that use contrast material. Preventing coronary artery disease. Lifestyle changes such as eating a low-fat diet, quitting smoking, and getting regular exercise can help reduce your overall risk of developing heart disease and stroke. For more information, see the topic Coronary Artery Disease. Weighing yourself daily so that you are aware of any rapid weight gain.

You may need emotional support during treatment for nephrotic syndrome. If you or your child has nephrotic syndrome and you are having a hard time handling treatment or the severity of your child's condition, talking with a doctor or seeking counseling may help. Treatment if the condition gets worse Sometimes treatment for nephrotic syndrome is unsuccessful. If this occurs, you may develop chronic kidney disease. Your doctor may recommend that you begin hemodialysis, peritoneal dialysis, or consider a kidney transplant. For more information, see the topic Chronic Kidney Disease. Clinical trials are ongoing to test more effective medicines for the treatment of steroid-resistant (relapsing) nephrotic syndrome. Ask your doctor about clinical trials if treatment has not successfully controlled your nephrotic syndrome. To participate in a clinical trial, you may need to travel to a large treatment center. Medications Nephrotic syndrome is usually successfully treated with a combination of medicines. Medication Choices Medicines to treat nephrotic syndrome include:

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Corticosteroids, such as prednisone or prednisolone, to reduce swelling. Albumin, to restore blood volume. Diuretics, such as bumetanide or furosemide, to help maintain fluid balance. Cyclophosphamide, cyclosporine, or CellCept, when treatment with corticosteroids is not successful.

Most children are successfully treated with corticosteroids, though relapses are common.7 Clinical trials are ongoing to test more effective medicines for the treatment of steroid-resistant (relapsing) nephrotic syndrome. Ask your doctor about information on clinical trials if treatment has not successfully controlled your nephrotic syndrome. To participate in a clinical trial, you may need to travel to a large treatment center. What To Think About

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Skin care when you have nephrotic syndrome Nephrotic syndrome may cause your skin to become dry and fragile, break open easily, bleed, and become infected. You can prevent or reduce additional skin problems by using these tips:

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Most children who have nephrotic syndrome do well with treatment and have a normal life expectancy. Children older than age 12 at the time of diagnosis and adults who also have diabetes or high blood pressure do not respond as well to treatment as do children younger than 12. Surgery

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Surgery is not used to treat nephrotic syndrome. But if treatment is not controlling your condition and you have developed chronic kidney disease, your doctor may recommend a kidney transplant. ************************** Living with nephrotic syndrome:

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Should I reduce my salt intake? What can I do about my dry skin? What medicines should I avoid if I have nephrotic syndrome?

serving size may increase your sodium beyond a healthy level. Avoid foods that contain monosodium glutamate (MSG) and disodium phosphate. Avoid canned foods. Avoid salted ham, potato chips, pretzels, salted nuts, and other salty snack foods.

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Check for areas that are red, warm to the touch, or bleeding. Use a mirror or ask someone else to look at your feet, back, or buttocks if you have trouble seeing these areas. Avoid excessive bathing. Soap and water deplete your skin of the essential oils that hold in moisture. o Limit showers or baths to 10 minutes. o Do not use hot water to bathe. o Use bath oils in the tub. (Be careful, because bath oil will make the tub slippery.) o Use mild soaps, such as Dove or Cetaphil, especially under the arms and in the genital area. Use a moisturizing lotion after you bathe, or more frequently if your skin tends to become dry easily. Avoid products that contain alcohol, because they can dry your skin. Avoid scratching your skin or rubbing it vigorously with towels. If itching is a problem, see relief from itching. Avoid chemicals that may irritate the skin, such as rubbing alcohol, soaps, detergents, or solvents. Use baking soda or cornstarch powders on areas of your skin that become irritated. Avoid powders that contain talc. Breathing in talc can irritate your lungs. Avoid tight-fitting clothes and shoes. Wear natural-fiber clothes that allow moisture to evaporate from your skin. Avoid wearing wool and acrylic fabrics next to your skin.

Reducing your salt intake Medications that can cause acute renal failure It's often a good idea to reduce the amount of salt (sodium) in your diet if you are diagnosed with certain conditions, such as nephrotic syndrome, Cushing's syndrome, or heart failure. Exactly how much daily salt is needed varies from person to person. Try some of these tips for lowering your salt intake:

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Flavor your foods with herbs and spices such as basil, tarragon, or mint, or use salt-free sauces or lemon juice. Try plain or flavored vinegar to flavor soups and stews. Use about 1 tsp (4.9 mL) of vinegar for every 2 qt (1.9 L) of soup or stew. Choose fresh or frozen vegetables and fruits. Include more grains and beans in your diet. Choose foods marked “low-salt” or “low-sodium.” Foods labeled this way must contain less than 140 mg of sodium per serving. Do not use salt during cooking or at the table. Talk to your health professional before using a salt substitute. It may not be recommended, because most salt substitutes contain potassium. Potassium can build up in the bodies of people with kidney disease and cause severe illnesses and even death. Avoid fast foods, prepackaged foods (such as TV dinners and frozen entrees), and processed foods (such as lunch meats and cheeses). Always check the serving size on processed food. Eating more than the single

Many medications can cause acute renal failure. Examples include:

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Antibiotics, such as aminoglycosides, cephalosporins, amphotericin B, bacitracin, acyclovir, and vancomycin. Blood pressure medicines called ACE inhibitors (such as captopril and ramipril) and angiotensin receptor blockers (ARBs). Medicines used for cancer treatment (chemotherapy), such as cisplatin, carboplatin, and methotrexate. Dyes (contrast media) used in medical imaging tests. Illegal drugs, such as heroin and methamphetamine. Medicines used to treat HIV (protease inhibitors), such as indinavir and ritonavir. Nonsteroidal anti-inflammatory drugs, such as ibuprofen, ketoprofen, or aspirin. Ulcer medicines such as cimetidine (Tagamet).

Other chemicals, such as insecticides, herbicides, and ethylene glycol, can also cause acute renal failure. http://health.yahoo.com/urinary-overview/nephrotic-syndrometopic-overview/healthwise--aa124985.html ************************************************** Childhood Nephrotic Syndrome

Childhood nephrotic syndrome can occur at any age but is most common between the ages of 1-1/2 and 8 years. It seems to affect boys more often than girls. A child with the nephrotic syndrome has these signs:

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High levels of protein in the urine Low levels of protein in the blood Swelling resulting from buildup of salt and water.

The nephrotic syndrome is not itself a disease. But it can be the first sign of a disease that damages the tiny blood-filtering units (glomeruli) in the kidneys, where urine is made. The kidneys are two bean-shaped organs found in the lower back. They are about the size of a fist. They clean the blood by filtering out excess water and salt and waste products from food. Healthy kidneys keep protein in the blood, which helps the blood soak up water from tissues. But kidneys with damaged filters may let protein leak into the urine. As a result, not enough protein is left in the blood to soak up the water. The water then moves from the blood into body tissues and causes swelling. You may see swelling around your child's eyes, belly, and legs. Your child may urinate less often than usual and may gain weight from the excess water. To diagnose childhood nephrotic syndrome, the doctor may ask for a urine sample to check for protein. The doctor will dip a strip of chemically treated paper into the urine sample. Too much protein in the urine will make the paper change color. Or the doctor may ask for a 24-hour collection of urine for a more precise measurement of the protein and other substances in the urine. The doctor may take a blood sample to see how well the kidneys are removing wastes. Healthy kidneys remove creatinine and urea nitrogen from the blood. If the blood contains high levels of these waste products, some kidney damage may have already occurred. But most children with the nephrotic syndrome do not have permanent kidney damage. In some cases, the doctor may want to examine a small piece of the child's kidney under a microscope to see if substances there are causing the syndrome. The procedure of collecting a small tissue sample from the kidney is called a biopsy, and it is usually performed with a long needle passed through the skin. The child will be awake during the procedure and receive calming drugs and a local painkiller at the site of the needle entry. General anesthesia is used in the very rare cases where open surgery is required. The child will stay overnight in the hospital to rest and allow the health care team to ensure that no problems occur. Minimal Change Disease The most common form of the nephrotic syndrome in children is called minimal change disease. Doctors do not know what causes it. The condition is called minimal change disease because children with this form of the nephrotic syndrome have normal or nearly normal biopsies. If your child is diagnosed with minimal change disease, the doctor will probably prescribe prednisone, which belongs to a class of drugs called corticosteroids. Prednisone stops the movement of protein from the blood into the urine, but it does have side effects that the doctor will explain. Following the doctor's directions exactly is essential to protect your child's health. The doctor may also prescribe another type of drug called a diuretic, which reduces the swelling by helping the child urinate. When protein is no longer present in the urine, the doctor will begin to reduce the dosage of prednisone. This process takes several weeks. Some children never get sick again, but most do develop swelling and protein in the urine again, usually following a viral illness. However, as long as the child continues to respond to prednisone and the urine becomes protein free, he or she has an excellent long-term outlook without kidney damage.

Children who relapse frequently, or who seem to be dependent on prednisone or have side effects from it, may be given a second type of drug called a cytotoxic agent. The agents most frequently used are cyclophosphamide, chlorambucil, and cyclosporine. After reducing protein in the urine with prednisone, the doctor may prescribe the cytotoxic agent for a while. Treatment with cyclophosphamide and chlorambucil usually lasts for 8 to 12 weeks, while treatment with cyclosporine frequently takes longer. The good news is that most children "outgrow" this disease by their late teens with no permanent damage to their kidneys. Other Conditions That Involve the Childhood Nephrotic Syndrome In about 20 percent of children with the nephrotic syndrome, the kidney biopsy reveals scarring or deposits in the glomeruli. The two most common diseases that damage these tiny filtering units are focal segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN). Very rarely, a child may be born with a condition that causes the nephrotic syndrome (congenital nephropathy). Since prednisone is less effective in treating these diseases than it is in treating minimal change disease, the doctor may use additional therapies, including cytotoxic agents. Recent experience with a class of drugs called ACE inhibitors (a type of blood pressure drug) indicates that these drugs help prevent protein from leaking into the urine and keep the kidneys from being damaged in children with the nephrotic syndrome. Hope Through Research The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports research to help many kinds of people with kidney disease, including children. NIDDK's Division of Kidney, Urologic, and Hematologic Diseases maintains the Pediatric Nephrology Program, which supports research into the causes, treatment, and prevention of kidney diseases in children, including minimal change disease, congenital nephrotic syndrome, primary glomerular disease, and postinfection glomerulonephritis. ************************ http://www.patient.co.uk/showdoc/27000748/ Nephrotic Syndrome

Nephrotic syndrome is a condition where the 'filters' in the kidney become 'leaky' and large amounts of protein leak from your blood into your urine. The main symptom is oedema (fluid retention) which is mainly due to the low protein level in the blood. Various diseases can cause nephrotic syndrome, some more serious than others. Treatment and outcome (prognosis) vary, depending on the cause. The common cause in children (minimal change disease) usually responds very well to treatment.

Understanding kidneys and urine The kidneys clear waste materials from the body and maintain a normal balance of fluids and chemicals in the body. The two kidneys lie to the sides of the upper abdomen, behind the intestines, and either side of the spine. Each kidney is about the size of a large orange, but bean-shaped. A large renal artery takes blood to each kidney. The artery divides into many tiny blood vessels (capillaries) throughout the kidney. In the outer part of the kidneys tiny blood vessels cluster together to form structures called glomeruli. Each glomerulus is like a filter. The structure of the glomerulus

allows waste products and some water and salt to pass from the blood into a tiny channel called a tubule, while keeping blood cells and protein in the bloodstream. Each glomerulus and tubule is called a 'nephron'. There are about one million nephrons in each kidney.

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proteins normally found in the bloodstream, the main protein that leaks from the blood into the urine is called albumin. A low blood level of albumin is a main feature of nephrotic syndrome. Fluid retention (oedema). This is a consequence of the low level of albumin in the bloodstream, and other complex factors not fully understood. A high blood level of cholesterol and other lipids (fats). This is due to the change in the balance of various protein levels in the blood due to the protein leakage. Normal kidney function, at least initially. This means that the 'waste clearing' function of the kidneys is not affected - at least not at first. However, some of the conditions that cause nephrotic syndrome can progress to cause kidney failure.

Other typical symptoms and signs of nephrotic syndrome are discussed later. What are the causes of nephrotic syndrome? Various diseases can affect the glomeruli and can result in nephrotic syndrome. The following gives a brief description of the main ones. Minimal change disease The name 'minimal change' comes from the fact that there is virtually no change detectable in the glomeruli if a sample of kidney is looked at under the microscope. Although the glomeruli look normal under the microscope, there seems to be some minor change in the glomeruli that allows leakage of protein. The cause of minimal change disease is not clear. It probably has something to do with a slight change in the immune system, or perhaps a 'reaction' of parts of the immune system to some unidentified factor.

As the waste products, water and salts pass along the tubule there is a complex adjustment of the content. For example, some water and salts may be absorbed back into the bloodstream, depending on the current level of water and salt in your blood. Tiny blood vessels next to each tubule enable this 'fine tuning' of the transfer of water and salts between the tubules and the blood. The liquid that remains at the end of each tubule is called urine. This drains into larger channels (ducts) which drain into the renal pelvis (the inner part of the kidney). From the renal pelvis the urine passes down a tube called a ureter which goes from each kidney to the bladder. Urine is stored in the bladder until it is passed out through the urethra when we go to the toilet. The 'cleaned' (filtered) blood from each kidney collects into a large renal vein which takes the blood back towards the heart. What is nephrotic syndrome? Nephrotic syndrome is not a single disease - it is a syndrome. A syndrome is a set of symptoms and signs that tend to occur together, and which can be caused by one or more different diseases. Nephrotic syndrome can be caused by many different diseases, some more serious than others. The 'hallmark' or main feature of nephrotic syndrome is that the kidneys leak a lot of protein. Normally, urine contains virtually no protein. In nephrotic syndrome the urine contains large amounts of protein. What happens is that filters in the kidneys (the glomeruli) become 'leaky' and protein, instead of remaining in the blood, leaks out into the urine. Protein in the urine is called 'proteinuria.' The other key features of nephrotic syndrome are:

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A low level of protein in the blood as a result of protein loss in the urine. Although there is a drop in many of the

Minimal change disease causes about 9 in 10 cases of nephrotic syndrome in children under the age of five years. It causes about 1 in 5 cases of nephrotic syndrome in adults. It usually responds well to treatment with steroid medication and does not cause kidney failure in most cases. Membranous nephropathy This is sometimes called membranous nephritis or membranous glomerulonephritis. It is a common cause of nephrotic syndrome in adults. It is an uncommon cause in children. In this condition there is some thickening of the membrane in the glomeruli (the 'filter' of the glomeruli) which makes the glomeruli 'leaky' to protein. The thickening can be seen under a microscope if a sample of kidney is taken for testing. In many cases, the cause or reason for this change to occur in the glomeruli is not known. However, there are various conditions that can result in membranous nephropathy developing. For example, an abnormal reaction of the immune system to some infections or drugs can cause this disease. Focal segmental glomerulosclerosis (FSGS) This is a condition where small 'scars' (sclerosis) develop on some glomeruli. The cause is unknown in most cases. However, a reaction of the immune system to 'something' or to various different things is thought to be the cause. FSGS accounts for up to 1 in 10 cases of nephrotic syndrome in children but a higher percentage of cases in adults. Other disorders of the glomeruli There are various other uncommon kidney disorders which primarily affect the glomeruli that can result in nephrotic syndrome. For example, membranoproliferative glomerulonephritis, mesangial proliferative glomerulonephritis, fibrillary glomerulosclerosis, diffuse mesangial sclerosis, IgM mesangial nephropathy. The cause of some of these conditions is

not clear. However, some are probably caused by reactions of the immune system that cause damage to specific parts of the glomeruli or nearby cells.

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Other general conditions A complication of some other more generalised conditions can cause damage to glomeruli resulting in nephrotic syndrome. For example, nephrotic syndrome is a possible complication of diabetes, SLE (systemic lupus erythematosus), rheumatoid arthritis, polyarteritis nodosa, Henoch-Schönlein purpura, various infections, various cancers, amyloidosis. It can also occur as a side effect of certain drugs, and as a consequence of various poisons or toxins.

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What are the symptoms of nephrotic syndrome? Oedema ('fluid retention') is a main symptom Oedema occurs when fluid leaks out of blood vessels into the body tissues. This causes swelling and 'puffiness' of the affected tissues. The swelling is usually painless, but the swollen tissues may feel 'tight'. With children, the face is often affected first and the face becomes 'puffy'. With adults, the ankles often become swollen at first (as gravity helps fluid to pool in the lower legs). As oedema becomes worse, the calves, then the thighs may become swollen. In severe cases of nephrotic syndrome, the oedema can become extensive. Fluid may accumulate in the lower back, the arms, in the abdominal cavity (ascites) or in the chest between the lungs and the chest wall (pleural effusion). The main reason why fluid leaks out from the blood vessels and into the body's tissues with nephrotic syndrome is because of a low level of protein in the blood. As protein is lost from the body in the urine, the body makes more protein in the liver which passes into the bloodstream. However, in time the amount made by the liver cannot keep up with the amount lost by the leaky kidneys, and so the blood level of protein goes down. If the blood level of protein is low then fluid tends to leak out of the blood vessels into the body tissues. (Protein and other chemicals in the blood exert an 'osmotic pressure' which tends to pull fluid into the blood vessels. If the concentration of protein reduces, the osmotic pressure reduces, and fluid leaks out.) Note: nephrotic syndrome is just one cause of oedema. There are other causes of oedema. For example, heart failure is the most common cause of oedema, especially in older people.

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An increased risk of developing infections. This is because you can lose antibodies in the urine. (Antibodies are proteins that help to defend the body from infection.) Any signs of infection (sore throat, fever, etc) should be taken seriously and reported promptly to a doctor. An increased risk of developing blood clots in the blood vessels (thrombosis). For example, a deep vein thrombosis (DVT) in a leg. This can cause pain, swelling and other complications. The reason for this is because there can be a change in the balance of proteins in the blood that protect against blood clots forming. A high cholesterol level. If this persists long-term it is a risk factor for developing heart disease. Increased risk of vitamin D deficiency which may lead to bone problems. This is due to loss of vitamin Dbinding protein from the bloodstream. Anaemia. This is due to loss of proteins that help to carry iron around in the bloodstream. You need iron to make red blood cells and to prevent anaemia.

Depending on the duration and severity of the nephrotic syndrome, you may be advised to take treatment to help prevent or counter these possible complications. Possible complications from the cause of the nephrotic syndrome You may also have various complications from the underlying condition which has caused the nephrotic syndrome. For example:

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One of the most common complications of kidney disorders is high blood pressure. Some kidney disorders lead to kidney failure. Some disorders (for example, diabetes, rheumatoid arthritis, etc) that cause nephrotic syndrome can have various other symptoms and complications.

Possible complications from treatment Often, the treatment of nephrotic syndrome requires a course of steroid medicines or other medicines to suppress the immune system (see below). Some people develop side-effects and complications from these treatments, especially if the treatment requires high doses, or is for long periods. Do I need any tests?

Other symptoms

To confirm nephrotic syndrome

Other symptoms that may develop include:

A simple 'dipstick' test of your urine can confirm that it contains a lot of protein. The amount of protein lost can be measured by more detailed urine and blood tests. A low blood level of albumin combined with a lot of protein found in the urine usually confirms that you have nephrotic syndrome.

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Your urine may appear frothy. Tiredness, lethargy and being off your food. If the nephrotic syndrome persists for a long time then you may develop wasting of your muscles, and your nails may become white. Depending on the cause of the nephrotic syndrome, you may also have other symptoms. For example, if you have nephrotic syndrome as a complication of rheumatoid arthritis you may have a range of other symptoms caused by the arthritis. Some conditions of the kidney can cause high blood pressure and/or kidney failure.

What are the possible complications? Possible complications from nephrotic syndrome itself Complications can be caused by nephrotic syndrome itself due to the loss of normal proteins from the blood. These include:

To find the cause of the nephrotic syndrome A range of blood tests may be done to try and identify the cause of the nephrotic syndrome. A kidney biopsy may also be done. A kidney biopsy is when a small sample of tissue is removed from a kidney. The sample is looked at under a microscope, or tested in other ways. This is often the most important test to clarify the cause of the nephrotic syndrome in adults. However, a biopsy is not usually done in children under the age of eight years. This is because most cases in young children are due to minimal change disease. A trial of treatment is usually advised first, and a biopsy done only if treatment does not work. (There are some exceptions to this general rule.) To check on the function of the kidneys Blood tests can check on the function of the kidneys. That is, how well they are clearing waste products from the bloodstream.

What is the treatment for nephrotic syndrome?

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Treatment of oedema

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Diuretics ('water tablets') help to clear the body of oedema. Diuretics work by acting on the cells in the kidney tubules to make them pass out more water rather than 'reabsorbing' water back into the bloodstream. So, you pass out more urine. The excess fluid in the body's tissues then passes back into the bloodstream to keep the blood volume up to normal. Your doctor may also advise you to limit the amount of salt in your diet to try and limit oedema. Treatment of high blood pressure Many people with kidney disorders have high blood pressure. If you develop high blood pressure then treatment is usually advised to bring your blood pressure down. A medicine called an ACE inhibitor is commonly used for this. Treatment of the underlying cause As mentioned, there are many causes of nephrotic syndrome. The treatment depends on the underlying cause. Some causes are more serious than others, some causes can be treated more easily than others. For example, treatment for minimal change disease usually works well to stop the leak of protein from the kidneys. The usual treatment for minimal change disease is a course of steroid medication which may last several months. In some cases, this is a 'one off' treatment and the disease does not return. In some cases of minimal change disease, the disease recurs from time to time which needs repeated courses of steroid medication. Steroids or other medicines called 'immunosuppressants' may be used to reduce inflammation and abnormal immune responses in various diseases that cause nephrotic syndrome. Your doctor will advise on the treatment options for each situation. What is the outlook (prognosis)? The outlook depends on the cause. For example, the most common cause of nephrotic syndrome in children (minimal change disease) usually responds well to treatment, and generally has a good outlook. The outlook is less good with some other conditions. Your doctor will be able to give an outlook for your particular condition. Further help and information Nephrotic Syndrome in Children Support Group 94 Bulford, Wellington, Somerset, TA21 8DH Tel: 01823 652 886 Web: www.nephrotic.co.uk Provides information for parents with affected children as well as to GPs and other health professionals. Membranous Glomerulonephritis Support Group Web: www.mgninfo.co.uk A UK based group for sufferers of membranous glomerulonephritis (membranous nephropathy).

*********************** http://www.patient.co.uk/showdoc/40000676/ Nephrotic Syndrome Description Nephrotic syndrome is a pattern of presentation of renal disease, rather than a single pathological entity or diagnosis. Nephrotic syndrome is also known as nephrosis and is defined by the presence of nephrotic-range proteinuria, oedema, hyperlipidemia, and hypoalbuminaemia. It has serious complications and must be on the differential diagnosis for any patient presenting with new onset oedema.1 Pathophysiology It comprises the following elements: Features of the nephrotic syndrome:

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Oedema is thought to occur due to the loss of plasma oncotic pressure secondary to hypoalbuminaemia, causing accumulation of fluid in the extracellular space; a decrease in intravascular volume is thought to cause renal hypoperfusion further enhancing salt and water retention. However, this model cannot fully explain all the pathophysiological and clinical features of the nephrotic syndrome and other, as yet unelucidated, intra- and extra-renal mechanisms may be responsible for the combination of biochemical and clinical features seen in nephrotic syndrome. Hypercholesterolaemia is thought to be caused by:

National Kidney Federation

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Travis L, eMedicine, Nephrotic Syndrome, 2005; Paediatric overview

Stimulation of the liver to increase synthesis of all plasma proteins (including the lipoproteins), due to their low level in the blood. Reduction of lipoprotein catabolism due to reduced levels of lipoprotein lipase in blood. Other consequences of nephrotic syndrome:3

References

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Glomerular dysfunction leading to excessive urinary protein excretion (formerly defined as >3.5 g/day but there appears to be individual variation around this cutoff figure) Hypoalbuminaemia as a result of urinary protein loss (albumin levels usually in range <25–30 g/l) Peripheral oedema due to hypoalbuminaemia Hypercholesterolaemia/dyslipidaemia

• Normal detoxifying renal function, at least initially The primary abnormality in nephrotic syndrome is thought to be loss of a layer of negatively-charged heparin sulphate within the glomerular basement membrane, that allows the increased passage of large amounts of low-molecular weight anionic proteins during ultrafiltration. However, recent research has shown that the loss of albumin in the urine may not be due to excessive filtration across the glomerular basement membrane as was previously supposed, rather a failure to reabsorb albumin after its ultrafiltration. It appears that renal disease may cause an impairment of the ability of cells in the proximal renal tubules to endocytose albumin that has been filtered across the glomeruli, and deliver it back into the blood supply around the renal tubules.2

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6 Stanley Street, Worksop, Nottinghamshire, S81 7HX Helpline: 0845 601 0209 Web: www.kidney.org.uk A national kidney charity run by patients, for patients.

Agraharkar M, Gala G, eMedicine, Nephrotic Syndrome, 2007. Hodson E, Willis N, Craig J; Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001533. [abstract]

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Decreased resistance to infections due to urinary immunoglobulin loss. Increased risk of arterial and venous thrombosis due to

loss of anti-thrombin III and plasminogen in the urine, combined with an increase in hepatic synthesis of clotting factors.

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Increased risk of osteitis fibrosa cystica and osteomalacia due to loss of vitamin D-binding protein and its complexes in the urine, through a combination of calcium malabsorption and secondary hyperparathyroidism. Epidemiology Nephrotic syndrome is a relatively rare but important manifestation of kidney disease. In the US, its annual incidence among children is reported to be 2–7 cases per 100,000.3 Incidence varies among adults depending on the incidence of underlying causes for the condition, particularly diabetes mellitus. Nephrotic syndrome has an incidence of around three new cases per 100 000 each year in adults.1

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Signs Clinical signs of nephrotic syndrome:1

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It can be caused by a wide range of primary (idiopathic) and secondary glomerular diseases.

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Primary renal diseases

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Minimal-change nephrotic syndrome (~85% of childhood cases) Focal segmental glomerulosclerosis (~9% of childhood cases) Mesangial proliferative glomerulonephritis (~2% of childhood cases) Membranous nephropathy (~3% of childhood cases) Membranoproliferative glomerulonephritis

Secondary renal diseases

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Postinfectious causes, e.g. Group-A beta-haemolytic streptococci, TB, malaria, syphilis, viruses such as VZV, HBV, HIV, infectious mononucleosis Collagen vascular diseases, e.g. SLE, rheumatoid arthritis, polyarteritis nodosa, Henoch-Schönlein purpura, vasculitides Metabolic diseases, e.g. diabetes mellitus, amyloidosis Inherited disease, e.g. Alport's syndrome, hereditary nephritis, sickle cell disease Malignant disease, e.g. multiple myeloma, leukaemia, lymphoma, carcinoma of breast/lung/colon/stomach Medications, e.g. NSAIDs, captopril, lithium, gold, diamorphine, interferon-alpha, penicillamine, probenecid and many others Toxins, e.g. bee sting, snake bites, phytotoxins Pregnancy, e.g. pre-eclampsia Transplant rejection

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Frothy urine

Oedema of dependent parts or generalised oedema are the main clinical findings. Facial oedema may be found in children. Occasionally, severely hypoalbuminaemic cases may have pleural effusions or ascites. Urinalysis will reveal gross proteinuria. Hypertension and haematuria are not usually found but may affect a minority of cases.

Investigations The aim of investigations is to find the underlying cause, direct future management, establish a baseline of severity and monitor response to treatment. The initial sequence is:1

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Symptoms In children facial swelling is a common presenting feature, with periorbital oedema often being the first evidence that something is wrong; oedema may progress to involve the whole body. Adults tend to present with peripheral oedema affecting the ankles and legs, which may progress to involve the whole body. Some patients may notice frothiness of their urine. Hypercoagulability may manifest as venous or arterial thrombosis, e.g. DVT, MI.

Periorbital oedema Lower limb oedema Oedema of the genitals Ascites Low albumin o Tiredness o Leukonychia Breathlessness o Pleural effusion o Fluid overload (high jugular venous pressure) o Acute renal failure Breathlessness with chest pain o Thromboemboli Dyslipidaemia o Eruptive xanthomata o Xanthelasmata Other

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Presentation

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Oedema

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Commoner causes of the nephrotic syndrome

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Recurrent infections and/or general fatigue, lethargy, poor appetite, weakness or episodic abdominal pain may cause presentation to a doctor.

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Confirm proteinuria present: urine dipstick positive Check for concomitant invisible (microscopic) haematuria: urine dipstick positive Exclude urine infection:urine microscopy/culture and sensitivity Measure amount of proteinuria: o Early morning urinary protein:creatinine ratio or albumin:creatinine ratio (mg/mmol) o Typically >300-350 mg/mmol in nephrotic syndrome Basic blood testing: o Full blood count and coagulation screen o Renal function including plasma creatinine and estimated glomerular filtration rate o Liver function tests to exclude concomitant liver pathology o Bone profile—corrected (for albumin) plasma calcium Check for other systemic diseases and causes of nephrotic syndrome: o C reactive protein and erythrocyte sedimentation rate o Glucose o Immunoglobulins, serum and urine electrophoresis o Autoimmune screen if an underlying autoimmune disease is suspected—antinuclear antibody (ANA), anti-double stranded DNA

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antibody (dsDNA), and complement values (C3 and C4) o Hepatitis B and C and HIV (after obtaining informed consent) Chest x ray and abdominal or renal ultrasound scan (especially if renal function is abnormal): o To check for pleural effusion or ascites o To check for the presence of two kidneys, their size and shape, and the absence of obstruction o To exclude malignancy and exclude other causes of oedema Be vigilant for complications such as thromboembolism: o Doppler ultrasound of leg veins in suspected deep vein thrombosis o Abdominal ultrasound, renal vein Doppler scan, venography of the inferior vena cava, computed tomography and magnetic resonance imaging of the abdomen if renal vein thrombosis is suspected o V/Q nuclear medicine lung scan, computed tomography pulmonary angiography for pulmonary embolism Investigate the underlying renal and systemic cause of nephrotic syndrome: o Renal biopsy under ultrasound (to assess size and structural condition of kidneys) o Obstructed or small kidneys may contraindicate renal biopsy o Make histological preparations for light microscopy, immunofluoresence or immunoperoxidase, electron microscopy

Most cases will require renal biopsy to determine the exact underlying cause of the condition; children under 8 years old usually have minimal-change nephrotic syndrome and so may be spared this investigation, especially if they are steroid-responsive. Adults with an obvious cause (e.g. diabetes with evidence of other complications) may be spared a biopsy at the discretion of a renal specialist. Other investigations to diagnose less usual causes such as abdominal fat/gingival biopsy to detect amyloidosis may be needed in place of or in addition to a renal biopsy. Diagnosis Diagnostic criteria for nephrotic syndrome:1

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Proteinuria greater than 3-3.5 g/24 hour or spot urine protein:creatinine ratio of >300-350 mg/mmol Serum albumin <25 g/l Clinical evidence of peripheral oedema

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Prognosis

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Severe hyperlipidaemia (total cholesterol often >10 mmol/l) is often present Initial management Initial management should focus on investigating the cause, identifying complications, and managing the symptoms of the disease.1 All patients should be referred to a nephrologist for further investigation, which often includes a renal biopsy.1 Indications for acute admission include:

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Severe generalised oedema, particularly if pleural effusion/oedema causing respiratory compromise Tense scrotal/labial oedema Complications of the nephrotic state (e.g. sepsis, pneumonia, MI, DVT, growth failure) Inability to comply with therapy/inability to cope with condition in family/independently Any features of a possible nephritic syndrome such as haematuria, hypertension and impaired renal function parameters Most cases do not require acute hospitalisation.

Reduce salt intake in diet (avoid processed foods and adding salt to food). Give diet with adequate calorific intake and sufficient protein content (1–2 g/kg daily).4 Hyperlipidaemia – does not initially require therapy but may do so if prolonged.4 Fluid restriction is not usually necessary (if severe enough to need this then may need admission).4 Referral to a renal service for urgent outpatient assessment is advisable, to confirm the mode of presentation and direct any future investigations/therapy. Oedema is treated through diuretic therapy with furosemide (~1 mg/kg/day) ± spironolactone (~2 mg/kg/day). Check weight regularly to assess response to diuretics and ensure fluid retention is not worsening, or that patient is over-diuresed. Patients with very low albumin levels may not respond to diuretics and may require admission to receive intravenous albumin therapy. Some children with severe oedema may be prescribed antibiotic prophylaxis against infection and this should usually be on the advice of a renal specialist. Most children will have minimal-change nephrotic syndrome and usually respond to a trial of steroid therapy under the direction of a renal specialist. Other forms of nephrotic syndrome are less treatment responsive; ACE inhibitors are frequently used in adults to some effect. In children who do not respond to steroids, and in some adults, treatment may be with other immunomodulatory drugs such as cyclophosphamide, ciclosporin, tacrolimus and levamisole.4

This is highly variable depending on the underlying cause. Congenital nephrotic syndrome usually carries a very poor prognosis. Outlook for the vast majority of children with minimalchange nephrotic syndrome is excellent; response to steroids is the norm, although there may be relapses and a need to use alternative immunomodulatory drugs. Since the introduction of corticosteroids, the overall mortality of primary nephrotic syndrome has decreased dramatically from over 50% to approximately 2-5%. Adult prognosis is variable and largely related to the underlying cause, its severity, progression and response to any treatment used to modify it.

Document references

1. 2.

3. 4.

Hull RP, Goldsmith DJ; Nephrotic syndrome in adults. BMJ. 2008 May 24;336(7654):1185-9. Russo LM, Sandoval RM, McKee M, et al; The normal kidney filters nephrotic levels of albumin retrieved by proximal tubule cells: Retrieval is disrupted in nephrotic states. Kidney Int. 2007 Jan 17;. [abstract] Agraharkar M, Gala G, Gangakhedkar AK; Nephrotic Syndrome. eMedicine, February 2007. Lane J; Nephrotic Syndrome. eMedicine, Dec 2008; Paediatric overview.