Nephrotic Syndrome: What You Need to Know
Medically reviewed by Kashif J. Piracha, MDMedically reviewed by Kashif J. Piracha, MD
Nephrotic syndrome is a group of symptoms that occur when your kidneys are not functioning as they should. It is not a disease but a condition caused by diseases that damage the tiny filtering blood vessels of the kidneys, called glomeruli. These include rare kidney diseases, like minimal change disease (MCD), and systemic (whole-body) diseases like lupus or diabetes.
Nephrotic syndrome is characterized by high cholesterol, low blood albumin (a type of protein), high protein in urine, and fluid overload in tissues. These can lead to symptoms like foamy urine, weight gain, puffy eyes, and swollen legs and feet. Adults and children can be affected, often for different reasons.
Treatment approaches for nephrotic syndrome are geared toward inducing remission. In some patients, this requires drug therapy; in others, there is spontaneous remission. Treatment aims to prevent kidney damage and potentially severe complications like deep vein thrombosis (DVT) and kidney failure.
This article describes the causes and symptoms of nephrotic syndrome, including how it is diagnosed and treated.
Toa55 / Getty Images
Nephrotic vs. Nephritic Syndrome
Nephrotic syndrome should not be confused with nephritic syndrome, a kidney condition caused by an abnormal immune reaction to an infection or disease. Nephritic syndrome causes the acute (sudden) inflammation of glomeruli and is distinguished by symptoms like hematuria (blood in urine), hypertension (high blood pressure), and reduced urine output.
What Causes Nephrotic Syndrome?
Nephrotic syndrome is caused either by a disease directly affecting the kidneys, called primary nephrotic syndrome, or a systemic disease that affects the kidneys and other organs, called secondary nephrotic syndrome.
Primary Nephrotic Syndrome
Primary nephrotic syndrome accounts for roughly 90% of nephrotic syndrome cases. It is caused by a category of kidney disease called glomerular disease, which affects the cluster of capillaries (called glomeruli) where protein and waste products are filtered from the blood.
Primary nephrotic syndrome is also known as idiopathic nephrotic syndrome because the underlying causes of these diseases are unknown (idiopathic).
These include:
Minimal change disease (MCD) is the most common cause in children, so named because the damage cannot be seen under a light microscope. MCD is thought to be linked to allergies, viral infections, or nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin.
Focal segmental glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome in Black adults. The disease, characterized by progressive scarring and destruction of glomeruli, is thought to be linked to genetics.
Membranous glomerulonephritis (MGN), a slowly progressive disease, is the most common cause of nephrotic syndrome in White adults. It is thought to be autoimmune (the immune system attacking the body's own tissues). MGN causes acute inflammation of glomeruli, resulting in protein leaking into the urine.
Rapidly progressive glomerulonephritis (RPGN) is a potentially serious condition seen mainly in adults. It causes rapid formation of lesions in the glomeruli. Also thought to be autoimmune, RPGN progresses so rapidly that kidney failure can occur in days to weeks.
Secondary Nephrotic Syndrome
Secondary nephrotic syndrome accounts for around 10% of nephrotic syndrome cases. It is associated with diseases that collaterally damage the kidneys. These include autoimmune diseases that damage the kidney with systemic inflammation or diseases that cause the obstruction of blood vessels, including those of the kidneys.
Common causes of secondary nephrotic syndrome include:
Diabetic nephropathy is when uncontrolled high blood sugar damages the kidney's filtering units.
Lupus nephritis is a complication of the autoimmune disease lupus. It can target and damage the kidneys with inflammation.
Sjögren's syndrome is an autoimmune disease that can cause immune protein deposits in the kidneys, triggering an inflammatory response.
Vasculitis is an autoimmune disease that causes inflammation of blood vessels, including in the kidneys.
Certain chronic viral diseases, such as HIV, hepatitis C, and hepatitis B, can cause persistent, low-level inflammation that progressively damages the kidneys.
Certain cancers, such as multiple myeloma, leukemia, and melanoma, disperse fragments of immune proteins into the bloodstream that can block glomeruli.
Amyloidosis is a group of diseases that produce abnormal proteins called amyloid fibrils that can block and damage glomeruli.
Sarcoidosis is an inflammatory disease that causes the formation of hardened granules (granulomas) in tissues, including those of the kidneys.
Syphilis is a bacterial sexually transmitted infection (STI) that can sometimes cause inflammatory kidney damage during the second stage of the infection.
Congenital nephrotic syndrome is a rare inherited disorder in infants that affects the production of a protein called nephrin, which is needed for normal kidney filtration.
Certain medications, including drugs like interferon A, lithium, heroin, and Aredia (pamidronate), may also lead to secondary nephrotic syndrome.
Symptoms of Nephrotic Syndrome
Nephrotic syndrome in adults and children is defined by four co-occurring conditions:
Proteinuria: Too much protein in the urine
Hypoalbuminemia: Low levels of a protein called albumin in your blood
Hyperlipidemia: High levels of cholesterol in your blood
Edema: The swelling of tissues due to the overload of fluid
These conditions together cause the symptoms commonly seen in people with nephrotic syndrome, including:
Foamy urine
Puffy eyelids and face
Swollen legs, ankles, and feet
Fatigue
Weight gain due to fluid retention
Nephrotic Syndrome in Children
Nephrotic syndrome is not very common in children. According to the National Institutes of Health, fewer than 5 in 100,000 children worldwide develop nephrotic syndrome each year. Children of any age can get nephrotic syndrome, but boys between the ages of 2 and 7 are most commonly affected.
In children, the first sign of nephrotic syndrome is usually a puffy face followed by swelling of the lower extremities. Other symptoms can develop, including nausea, diarrhea, muscle cramps, and blood in urine.
A Note on Gender and Sex Terminology
Verywell Health acknowledges that sex and gender are related concepts, but they are not the same. To accurately reflect our sources, this article uses terms like “female,” “male,” “woman,” and “man” as the sources use them.
Nephrotic Syndrome in Adults
Nephrotic syndrome is even less common in adults, affecting 3 in every 100,000 people in the United States each year.
In adults, the first sign is usually swelling of the lower extremities, arms, hands, and genitals (referred to as dependent or gravitational edema).
However, the early signs are often subtle and easily attributed to other causes, such as heart disease. The swelling and subsequent weight gain can also be missed if the person is overweight or has obesity.
In some cases, nephrotic syndrome is only recognized when symptoms of a severe complication, like kidney failure or a blood clot, occur.
Complications of Nephrotic Syndrome
Left untreated, the combination of proteinuria, hypoalbuminemia, hyperlipidemia, and edema can affect multiple organ systems. This can cause adverse changes in blood pressure, blood composition, the volume of body fluids, and the balance of electrolytes (charged minerals like sodium, calcium, and potassium) in the body.
Some of the more serious complications of nephrotic syndrome include:
Thrombus (blood clots): These occur when compounds that regulate clotting leak out of damaged glomeruli. This increased clotting can lead to serious complications like portal vein thrombosis (PVT) affecting the kidneys, deep vein thrombosis (DVT) affecting the legs, and pulmonary embolism (PE) affecting the lungs.
Cardiomegaly: Persistent edema can lead to the enlargement of the heart muscle, known as cardiomegaly. This, in turn, can lead to serious complications like heart failure, arrhythmia (irregular heartbeats), heart attack, and stroke.
Hypocalcemia: When vitamin D is depleted due to glomerular leakage, it can also lower calcium levels, leading to hypocalcemia. In severe cases, hypocalcemia can lead to depression, paresthesias (abnormal sensations), parkinsonism (slowed movements, muscle rigidity, and tremors), and seizures.
Infections: Along with protein, antibodies that regulate immunity can leak into urine. This may increase the risk of urinary tract infections (UTIs), respiratory infections, bacterial skin infections, peritonitis, and, in severe cases, septicemia and sepsis.
Acute kidney failure: When the body loses too much fluid (hypovolemia), the kidneys can lose their ability to filter blood, causing toxins to accumulate. This can lead to heart palpitations, shortness of breath, nausea, vomiting, and, in extreme cases, metabolic acidosis and death.
How Long Can I Live With Nephrotic Syndrome?
The survival rate for nephrotic syndrome is highly variable. While studies suggest that the three-year mortality rate for primary nephrotic syndrome is only 2% (meaning that two of every 100 people will die within three years), the number jumps to 25% by age 60. The most common cause of death is heart disease.
In contrast, people with secondary nephrotic syndrome have a lower risk of death than those with primary nephrotic disease but a greater risk of progression to end-stage kidney disease within three years (35% vs. 8%).
Related: What Are the Signs of Kidney Failure?
How Nephrotic Syndrome Is Diagnosed
The diagnosis of nephrotic syndrome starts with a review of your medical history and a physical examination to check for signs of edema. This includes pressing on swollen tissues with a thumb to see if it leaves an indentation.
The physical would be followed by a battery of urine and blood tests to check for the presence of proteinuria, hypoalbuminemia, and hyperlipidemia. Along with the presence of edema, nephrotic syndrome can be definitively diagnosed based on the following urine and blood test results:
Diagnosis | Test type | Results |
Proteinuria | Greater than 300 to 350 milligrams of protein per micromole of creatinine (mg/mmol) | |
Greater than 3 to 3.5 grams (g) of protein | ||
Hypoalbuminemia | Less than 2.5 grams of albumin per deciliter of blood (g/dL) | |
Hyperlipidemia | Over 350 milligrams of cholesterol per deciliters of blood (mg/dL) |
Additional tests would be ordered to diagnose the possible causes of nephrotic syndrome and to check for possible complications.
This may involve:
Renal function tests: Blood and urine tests used to detect kidney disease
D-dimer tests: A blood test that can help diagnose blood clots
Renal ultrasound: A non-invasive imaging study used to detect kidney damage
Doppler ultrasound of the leg: A type of ultrasound used to check for DVT
Chest X-ray: Used mainly to check for signs of PE
Immunological tests: A battery of blood tests used to detect autoimmune disease
Kidney biopsy: Used to obtain tissue samples to check for signs of primary nephrotic syndrome
Related: How Kidney Disease Is Diagnosed
Nephrotic Syndrome Treatment Options
The treatment of nephrotic syndrome is focused largely on managing symptoms and avoiding disease progression. This may involve medications and nutritional therapies that can help restore protein, albumin, cholesterol, and fluid levels back to normal.
Other treatments may be prescribed depending on the underlying cause of nephrotic syndrome. A kidney specialist known as a nephrologist oversees the treatment.
Medications
Different drugs treat various aspects of nephrotic syndrome. The drugs are usually taken by mouth, but severe cases may require intravenous (IV) infusions into a blood vein.
Among the drug options:
Angiotensin-converting enzyme (ACE) inhibitors like Privnil (lisinopril), Vasotec (enalapril), and Zestril (lisinopril) help lower blood pressure and the amount of protein released into urine.
Angiotensin II receptor blockers (ARBs) work similarly to ACE inhibitors and include drugs like Atacand (candesartan), Cozaar (losartan), and Diovan (valsartan).
Diuretics ("water pills") like Lasix (furosemide) and Aldactone (spironolactone) can reduce edema and blood pressure by promoting urination.
Statin drugs like Crestor (rosuvastatin), Lipitor (atorvastatin), Pravachol (pravastatin), and Zocor (simvastatin) can reduce blood cholesterol.
Immunosuppressants like cyclosporine, prednisone, and Rituxan (rituximab) can help control some primary causes of nephrotic syndrome. They may also help treat secondary autoimmune causes like lupus and vasculitis.
Anticoagulants (blood thinners) like warfarin, heparin, Eliquis (apixaban), and Xarelto (rivaroxaban) can reduce the risk of blood clots that lead to DVT and PE.
Managing Nephrotic Syndrome With Diet
Nephrotic syndrome is not treated with drugs alone. This is especially true with conditions like hypoalbuminemia, which is mainly treated with diet. Other dietary interventions can increase protein and lower cholesterol levels in the blood.
Dietary plans for people with nephrotic syndrome need to be tailored and managed to ensure that the therapeutic and nutritional goals are met. Working with a dietitian or qualified nutritionist often helps.
During acute illness, the following dietary measures are usually taken:
Increased protein: Your protein intake would need to be supplemented to make up for the loss of protein in urine. Plant-based proteins like beans, soy, and tofu are especially good for this.
Carbohydrates: It is recommended that you reduce your intake of simple carbohydrates (found in processed and sugary foods) and increase your intake of complex carbohydrates (like whole grains and beans).
Dietary fat: In addition to eating healthy polyunsaturated and monosaturated fats and avoiding unhealthy saturated and trans fats, the daily dietary fat intake would need to be restricted to less than 30% of the total calories for children and even less for adults.
Sodium restriction: A "no added salt" approach must be followed. Salty foods, including processed and canned foods that are typically high in sodium, would also be limited.
Fluid restriction: This is only needed for people with severe edema. Mild to moderate edema can usually be managed with diuretics.
Supplements: Your nephrologist may recommend supplements like calcium, vitamin D, iron, copper, and zinc, which may be depleted due to damaged glomeruli.
Even during periods of remission, good eating habits may help reduce your risk of a relapse.
Related: What Is the Best Diet for Kidney Disease?
Is Nephrotic Syndrome Curable?
Technically, nephrotic syndrome is not "curable." Instead, it is characterized by periods of remission (low disease activity) and relapse (the return of disease).
This is not to say that all people experience nephrotic syndrome in the same way.
While many people with nephrotic syndrome can achieve remission with treatment, others may achieve "spontaneous remission," during which the disease will suddenly clear on its own.
This is especially common with primary nephrotic syndrome, in which 30% of people will experience spontaneous remission while 30% will progress to kidney failure.
Among children with MCD, relapses tend to decrease with age and may stop altogether by the teen years. Because there is a potential for relapse, this is not described as a "cure" but rather a "sustained remission" (meaning the absence of symptoms for 12 months). Even so, the likelihood of relapse after many years remains low.
In other cases, nephrotic syndrome is not curable. This includes children with congenital nephrotic syndrome who tend to have progressively worsening symptoms and an increased risk of kidney failure.
Summary
Nephrotic syndrome is a disease that damages the filtering units of the kidneys called glomeruli resulting in these four conditions—proteinuria, high cholesterol, low blood albumin, and edema.
There are primary causes that directly damage the kidneys and secondary causes in which another disease indirectly damages the kidneys. Symptoms include fatigue, foamy urine, weight gain, puffy face, and swollen legs and feet.
Nephrotic syndrome can be diagnosed with a physical exam and a combination of urine and blood tests. The treatment involves medications and diet that help ease symptoms and avoid disease progression. Some cases resolve spontaneously.
Read the original article on Verywell Health.
