What is Nephrotic Syndrome?

Nephrotic syndrome is a collection of signs and symptoms which indicate that there is a problem with the kidneys. It is a syndrome rather than a disease. A syndrome is a group of symptoms that often occur together and typically develop as a result of another condition or underlying medical problem.

There can be various underlying conditions or problems, all of which require specific treatment. It can occur among adults and children but is more common among children, especially children aged between 18 months and four years.^[1] In children under 8 years old, boys are more commonly affected than girls.

While the prognosis is usually quite good, nephrotic syndrome can become severe and even potentially life-threatening, if left untreated. The degree of severity depends on the underlying cause.

The major symptoms of nephrotic syndrome include:

• The excretion of abnormally large amounts of protein, especially albumin, in the urine, known as proteinuria generally and albuminuria specifically
• Reduced levels of protein in the blood
• Edema, abnormal accumulations of fluid, causing swelling of the body or parts of it

Hypertension (high blood pressure) and thrombotic events (blood clots) may also be present, as might hyperlipidemia, a high level of lipids in the blood.

Causes of nephrotic syndrome include kidney damage from nephrotoxic drugs (drugs that are potentially damaging to the kidneys), systemic disorders such as diabetes or lupus, or diseases affecting the kidneys directly, such as glomerulonephritis.^[2] In children, most cases of nephrotic syndrome are caused by minimal change disease (MCD).

Treating nephrotic syndrome usually involves managing hypertension and hyperlipidemia, as well as relieving edema and stopping or lessening the loss of protein in the urine. Ways to do this include following a specific diet and taking medication to lower lipid levels and manage hypertension.^[3][4] If the nephrotic syndrome is caused by minimal change disease, steroids may be used as part of treatment.^[2]

How is nephrotic syndrome different to nephritic syndrome?

Nephritic syndrome is an inflammatory kidney disorder that is sometimes confused with nephrotic syndrome during initial diagnosis. However, there are several clear differences that are determined during laboratory testing. While the nephritic syndrome is characterized by inflammation and hematuria (blood in urine), nephrotic syndrome is mostly characterized by proteinuria.

Of the two, nephrotic syndrome is often the more serious, depending on the underlying cause. In both cases, medical assistance should be sought out as quickly as possible.

Symptoms and complications of nephrotic syndrome

Symptoms of nephrotic syndrome include:^[1][5][6]

• Appetite loss
• Malaise, a general feeling of unwellness
• Frothy urine due to proteinuria
• Edema; accumulated fluid under the skin, which may appear as weight gain
• Hyperlipidemia; high cholesterol or other high blood lipid values
• Hypertension; high blood pressure
• Hypoalbuminemia and albuminuria, low blood levels and high urine levels of the protein albumin

Proteinuria and edema are the two most distinctive symptoms of the nephrotic disorder.

Proteinuria in nephrotic syndrome

In a healthy kidney, small groupings of capillaries, known as glomeruli, filter the blood. The glomerulus and nearby tube for the removal of byproducts, known as a tubule, together make up a structure called a nephron.^[7]

In the nephron, the glomerulus filters the blood. Substances needed by the body, such as potassium, protein, and phosphorus, return to the blood, while unwanted products pass through a membrane into the tubule. These unwanted products pass from the tubule to the ureter, to the bladder and are eventually passed out of the body in the urine. If the tubule, glomerulus, or both, become damaged or infected, this filtration system may become unbalanced. Waste products may build up in the body, and necessary substances such as proteins and minerals may be lost, instead of being reabsorbed.^[7]

In glomerular disorders, such as some of those that lead to nephrotic syndrome, the membrane between the glomerulus and the tubule may lose its ability to prevent protein molecules and red blood cells from passing out into the tubule, for various reasons.^[8]

Healthy glomeruli allow less than 400mg of protein into urine per day. In nephrotic syndrome, three grams or more of protein pass into the urine and are subsequently lost, causing blood protein levels to fall.^[2] Nephrotic range proteinuria is defined as 3 to 3.5 or more grams of protein lost in urine over a twenty-four-hour period.^[5] This is almost eight times the amount of protein a healthy glomerulus would allow through.

This has various effects on the body, as protein loss causes low levels of blood protein. Because blood protein is vital to the absorption and elimination of extra fluid from the body’s tissues, low levels of protein result in a buildup of fluids in the tissues, known as edema.

Edema , ascites and pleural effusion

In nephrotic syndrome, the lack of protein leads to a buildup of fluid made up of sodium and water in the tissues. It is usually starting in the face, around the eyes, or in the legs and ankles, but may lead to generalized swelling of the entire body, too. ^[9][10] It can also lead to fluid build-up around the lungs.^[11] This is known as pleural effusion, and if this happens, the affected person may experience difficulty breathing and breathlessness. If this is the case a doctor should be consulted urgently. If fluid builds up inside the belly this is called ascites and may be uncomfortable. Ascites can lead to an increased abdominal circumference and a feeling of heaviness and discomfort in the stomach area or the entire belly.

While edema is generally not serious most of the time, it can among others cause joint and abdominal pain that is a cause of concern for people affected. If someone is not sure what causes their particular symptoms it is always advisable to see a doctor to get a proper diagnostic workup..

Ascites

Ascites are a common complication in disorders that involve proteinuria, such as nephrotic syndrome. In ascites, fluid accumulates inside the abdominal cavity, causing the abdomen to distend.[12] Ascites caused by the nephrotic syndrome are more common among children than adults.^[13] Symptoms of ascites include:^[12]

• Abdominal pain
• A swollen abdomen
• Weight gain
• Feeling full sooner during meals
• Shortness of breath

Ascites have to be treated by a doctor, and anyone who develops ascites should seek medical help as soon as possible.^[12] In nephrotic syndrome, treatment for ascites involves treating the underlying condition. In addition to this, some cases of ascites may need to be drained using a process called therapeutic paracentesis.

Pleural effusion

A pleural effusion is the buildup of an unusually large amount of fluid around the lungs between the layers of the pleura, the thin membrane that lines the inside of the chest cavity, and the surface of the lungs.^[14] Symptoms of pleural effusion include:^[15]

• A dry cough
• Shortness of breath
• Chest pain
• Difficulty breathing properly or worsening of shortness of breath while sitting or lying down

The treatment of pleural effusion depends on the degree of discomfort it is causing, whether it is obstructing breathing and what is causing it. Treating pleural effusion caused by nephrotic syndrome involves treating the underlying condition, but can also involve draining the fluid in a procedure called thoracentesis.^[15][16]

If you are concerned that you or someone you know is experiencing ascites or pleural effusion because of nephrotic syndrome, You can search for the nearest doctor Find my doctor.

Causes of nephrotic syndrome

Nephrotic syndrome is not a disease in itself, but rather a sign that something else is wrong in the body. Underlying conditions that can cause nephrotic syndrome can be primary, originating in the kidneys, or secondary, originating elsewhere in the body. Primary causes include:^[1][17][18]

• Minimal change disease, which can cause proteinuria, mostly found among children
• Focal segmental glomerulosclerosis, which causes scarring of the glomeruli
• Membranous nephropathy, which occurs when the glomeruli become thickened and damaged

Secondary causes include:^[1][19][20]

• Diabetic nephropathy, which results from long-term high levels of blood glucose
• Preeclampsia, a pregnancy complication
• Amyloidosis, a bone-marrow disorder that causes malformed protein chains, mostly found among older adults
• HIV-associated nephropathy

Some drugs may lead to kidney damage, which may then in some cases lead to nephrotic syndrome. Nephrotoxic drugs that can cause kidney damage in children include:^[21]

• Cyclosporine
• Aminoglycoside antibiotics
• Cisplatin
• Amphotericin B
• Beta-lactam antibiotics
• Indomethacin

It should be noted that the circumstances in which these drugs can become nephrotoxic vary from case to case and it is always advisable to talk to your doctor if you are worried about medication side effects.

Other drugs that can be nephrotoxic include:^[22]

• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Radiocontrast media
• Antirheumatic drugs
• Certain anticancer drugs

In cases where a certain drug may be causing the nephrotic syndrome, stopping using the drug usually improves the symptoms and relieves the syndrome.

Nephrotic syndrome in adults

Glomerulonephritis is the most common cause for nephrotic syndrome. The two most common subtypes of glomerulonephritis are focal segmental glomerulosclerosis (FSGN) and membranous glomerulonephritis, also known as MGN or membranous nephropathy. FSGN is the most common form of glomerulonephritis among people of African or African-American ancestry, while MGN is the most common among people of European ancestry.

There are many other causes for nephrotic syndrome, the most common being diabetes, and systemic lupus erythematosus.^[9] Glomerulonephritis can also be the result of a streptococcal infection. While some cases of glomerulonephritis clear up on their own, others may take longer. In cases where glomerulonephritis becomes chronic, long-term damage to the kidneys may occur.^[23]

The various types of glomerulonephritis are characterized by change or damage to the structures of the glomerulus, for example as a result of an attack by the body’s own immune system, infection, or exposure to toxins. It can lead to nephrotic syndrome, but also to another different syndrome called a nephritic syndrome. In most cases of nephrotic syndrome, the underlying condition affects the membrane between the tubule and the glomerulus, which causes the loss of protein in the urine.

The causes of the inflammation of the glomeruli that characterize focal segmental glomerulonephritis (FSGN) are not well-understood, but it is suspected that viral infection or exposure to toxins may be at least part of the problem. In most cases of membranous nephropathy, the cause for the damage to the glomerular membranes can be considered a result of an autoimmune attack on the glomeruli, leading to the person affected producing antibodies against their own glomerular membrane.^[24] This is called primary MGN. Secondary MGN can be caused by certain painkillers, known as NSAIDs, Hepatitis B and C, systemic lupus erythematosus, or other conditions, particularly other infections, but rarely also secondary due to tumors.

Nephrotic syndrome in children

Although nephrotic syndrome can affect people of any age, it often affects children between the ages of eighteen months and five years. Below the age of 8, more boys than girls are affected. While most cases of nephrotic syndrome in children can be treated and managed quite well (see the ‘Treatment’ section of this resource), some cases or underlying conditions causing nephrotic syndrome are congenital and more difficult to manage. However, the most common form of the nephrotic syndrome among children, minimal change disease, is not congenital.

Minimal change disease

Minimal change disease is the cause of up to 90% of cases of the nephrotic syndrome among children older than one year.^[25] Although adults can have minimal change disease, it is very rare among adults. Most cases of minimal change disease respond very well to treatment with steroids (see the ‘Treatment’ section of this resource).

If you are concerned that your child, or a child you care for, may have one of these kidney problems, You can search for a doctor near you My Doctor at any time.

Congenital nephrotic syndrome

Congenital nephrotic syndrome is, generally, a very rare form of nephrotic syndrome that affects children from infancy; symptoms often appear in the child’s first three months of life.^[26] The congenital nephrotic syndrome often does not respond well to treatment, and it is possible for the condition to become quite severe and for kidney failure to develop before the age of ten.

End-stage renal disease may develop before puberty, although treatment can postpone this.^[26] Congenital nephrotic syndrome is hereditary and is sometimes known as familial nephrotic syndrome.

Diagnosis of nephrotic syndrome

Nephrotic syndrome is initially diagnosed using urine testing, as well as a physical examination. Visible edema is considered a sign that kidney function might be disturbed, but urine tests for protein generally, and albumin, in particular, are considered more specific tests.^[27]

Albumin levels can be determined by a dipstick test, but a larger urine sample is needed if diagnosis if to be confirmed. Formerly, a twenty-four-hour collection of the affected person’s urine would be tested for albumin, but this is now often replaced by a more convenient single-sample test.^[11]

A common urine test performed by medical professionals is a test on a single urine sample, which is often gathered first thing upon waking.^[28] This test measures albumin and creatinine in ratio. A ratio of 30mg of albumin to one gram of creatinine signals that there is a problem.^[5] Urine samples will also be checked for lipids and cell casts, which are microscopic structures that may be produced by the kidneys if nephrotic syndrome or other disorders are present.^[1]

Also depending on the result of the urine test, different blood tests will be carried out to help in determining what the underlying cause of the nephrotic syndrome might be.
Blood tests for underlying causes may include:^[1]

• Blood glucose levels and HbA1c to determine whether diabetes is present.
• Hepatitis B and C tests
• Rheumatoid factor
• HIV antibody tests
• Serologic syphilis tests

While these tests can usually identify many causes, a kidney biopsy may additionally be needed to diagnose and clearly confirm the underlying cause and help in finding the best treatment option.^[5]

In children, treatment with steroids is often begun without waiting for biopsy results. This is because the nephrotic syndrome is usually the result of minimal change in disease. A biopsy may be likewise unnecessary in the case of adults with diabetes, given that diabetic nephropathy is a very common underlying cause.^[6]

Treatment of nephrotic syndrome

Treatment of nephrotic syndrome usually involves a combination of supportive treatment intended to reduce symptoms such as proteinuria, edema, hypertension, and hyperlipidemia, and treatment of the underlying cause.^[2] Steps should also be taken to prevent possible complications.^[27]

While some cases of nephrotic syndrome clear up whether or not treatment is administered, it is generally not advisable to wait and see, and medical advice should be sought without delay.^[6] Prognosis in cases of nephrotic syndrome is generally good, but this greatly depends on the underlying cause and how effectively it is treated.

Treatment may include:^[1][2][5]

• Angiotensin-converting-enzyme (ACE) inhibitors
• Angiotensin receptor blockers (ARB)
• Diuretics to reduce blood pressure and edema
• Salt/sodium restriction in the diet
• Statins to lower cholesterol

ACEs and ARBs lower blood pressure, which reduces the pressure inside the glomeruli. They thereby also prevent protein loss in the urine. Increasing protein consumption in the diet does not alleviate protein loss and is generally not advised. Blood-thinning medications should generally only be prescribed if the affected person has had a blood clot already. If possible, people with nephrotic syndrome should be vaccinated against pneumococcal disease and are advised to get yearly flu shots.^[5]

In children, nephrotic syndrome is often treated with corticosteroids such as prednisone or prednisolone.^[29]

Complications of nephrotic syndrome

Nephrotic syndrome can cause complications due to the way it may unbalance bodily systems. Complications can include:^{[1][5][11][30][31]}

• Hypothyroidism
• Protein undernutrition, in children
• High cholesterol (hyperlipidemia or hypercholesterolemia, due to changes in blood composition resulting from protein loss
• Coronary artery disease, in adults
• Blood clots (hypercoagulability), which occur because of abnormal protein levels in the blood
• Thrombosis in the lungs, limbs, kidney vessels or brain
• Anemia, due to a mechanism yet not fully understood, iron no longer being adequately transported in the blood
• Acute kidney injury, sudden, temporary loss of kidney function
• Hematuria, blood in the urine
• Severe azotemia, high levels of nitrogen compounds in the blood
• Infections, such as cellulitis, a skin infection, pneumonia, meningitis and spontaneous bacterial peritonitis, which may be more likely than in healthy people, due to a loss of immunoglobulins.

Good to know: Immunoglobulins are proteins that form part of the immune system and help to fight disease and infections. If they are increasingly lost, the body is at increased risk of infections.

Hypercoagulability and hyperlipidemia are not merely complications, but also classic features of nephrotic syndrome. Both states are the result of increased protein loss and the following protein synthesis. As albumin is lost in the urine, as part of the nephrotic syndrome, the liver is trying to compensate by producing more. Because protein synthesis is rather unspecific and not all proteins are being lost in the urine, the levels of some proteins in the blood, e.g. lipoproteins, actually rise. Simplified, increased lipoprotein levels lead to rising fat levels in the blood.

Good to know: Hypoalbuminemia (low albumin in the blood) can sometimes also manifest as white bands in the nails, known as Muerkhe’s Lines.^[27]

Nephrotic syndrome FAQs

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1. MSD Manuals. “Overview of Nephrotic Syndrome” January 2018. Accessed 5 April 2018. ↩ ↩ ↩ ↩ ↩ ↩ ↩ ↩

2. Kidney Care UK. “Nephrotic Syndrome”. Accessed 5 April 2018. ↩ ↩ ↩ ↩ ↩ ↩

3. Medscape. “Nephrotic Syndrome Treatment & Management”. 11 October 2018. Accessed 06 November 2018. ↩

4. Nature Reviews Nephrology. “Dyslipidaemia in nephrotic syndrome: mechanisms and treatment”. November 2017. Accessed 06 November 2018. ↩

5. National Institute of Diabetes and Digestive and Kidney Diseases. “Nephrotic Syndrome in adults”. February 2014. Accessed 9 April 2018. ↩ ↩ ↩ ↩ ↩ ↩ ↩ ↩

6. Edinburgh Royal Infirmary Renal Unit. “More info on nephrotic syndrome” April 2010. Accessed 5 April 2018. ↩ ↩ ↩

7. Kidneyhealthcare.com. “The Nephron – Structure and Function of the Nephron”. Accessed 5 April 2018. ↩ ↩

8. National Institute of Diabetes and Digestive and Kidney Diseases. “Glomerular Diseases”. Accessed 4 April 2018. ↩

9. Medscape. “Nephrotic Syndrome”. 11 October 2018. Accessed 06 November 2018. ↩ ↩ ↩

10. Frontiers in Pediatrics. “Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome”. January 2016. 06 November 2018. ↩

11. National Kidney Federation. “Nephrotic Syndrome (Adults)”. 1999. Accessed 9 April 2018. ↩ ↩ ↩

12. Amboss. “Ascites”. 1 August 2018. Accessed 1 October 2018. ↩ ↩ ↩

13. Journal of Clinical Gastroenterology. “Ascites in Nephrotic syndrome. Incidence, patients’ characteristics, and complications.”. January 1996. Accessed 1 October 2018. ↩

14. WebMD. “What Is a Pleural Effusion?”. Accessed 2 October 2018. ↩

15. Cleveland Clinic. “Pleural Effusion Causes, Signs & Treatment”. Accessed 2 October 2018. ↩ ↩

16. Johns Hopkins Medicine. “Thoracentisis”. Accessed 06 November 2018. ↩

17. National Kidney Foundation. “Focal Segmental Glomerulosclerosis (FSGS)”. Accessed 9 April 2018. ↩

18. UNC Kidney Centre. “Membranous Nephropathy”. Accessed 9 April 2018. ↩

19. Amyloidosis Foundation. “AL Amyloidosis”. Accessed 9 April 2018. ↩

20. Kidney and Urology Foundation of America. “Nephrotic Syndrome in Adults”. Accessed 9 April 2018. ↩

21. Journal of Paediatric Nephrology. “Nephrotoxic drugs.”. October 1988. Accessed 9 April 2018. ↩

22. Japanese Journal of Clinical Medicine. “Drug induced nephrotic syndrome”. October 2004. Accessed 9 April 2018. ↩

23. Patient.info. “Glomerulonephritis”. 21 May 2018. Accessed 20 April 2018. ↩

24. Clinical Journal of the American Society of Nephrology. “Primary Membranous Nephropathy.”. June 2017. Accessed 28 November 2018. ↩

25. Clinical Journal of American Society of Nephrology. “Minimal Change Disease”. February 2017. Accessed 1 October 2018. ↩

26. Genetics Home Reference. “Congenital nephrotic syndrome”. Accessed 1 October 2018. ↩ ↩

27. RenalMed. “Nephrotic Syndrome”. Accessed 9 April 2018. ↩ ↩ ↩

28. Journal of the American Society of Nephrology. “First Morning Voids Are More Reliable Than Spot Urine Samples to Assess Microalbuminuria”. February 2009. Accessed 06 November 2018. ↩

29. Cochrane. “Corticosteroid therapy for children with nephrotic syndrome”. 18 March 2015. Accessed 2 October 2018. ↩

30. Nephrotic Syndrome Trust. “What is Nephrotic Syndrome?”. Accessed 5 April 2018. ↩

31. Pediatric Nephrology. “Anemia in nephrotic syndrome: approach to evaluation and treatment.”. August 2017. Accessed 06 November 2018. ↩

32. MedicineNet.com. “Nonsteroidal Anti-inflammatory Drugs (NSAIDs)”. Accessed 17 April 2018. ↩

33. NEJM Journal Watch. “Nephrotic syndrome from NSAIDS.” May 18 1990. Accessed 17 April 2018. ↩

34. Pharmaceuticals (Basel). “Nonsteroidal Anti-Inflammatory Drugs and the Kidney”. July 2010. Accessed 17 April 2018. ↩

35. Seminars in Nephrology. “Interstitial nephritis, the nephrotic syndrome, and chronic renal failure secondary to nonsteroidal anti-inflammatory drugs.”. May 1995. Accessed 17 April 2018. ↩ ↩

36. UpToDate. “Clinical manifestations and diagnosis of acute interstitial nephritis”. Accessed 17 April 2018. ↩ ↩

37. DaVita. “What is dialysis and when do I start?”. Accessed 17 April 2018. ↩

38. Pediatric Nephrology. “Hereditary nephrotic syndrome: a systematic approach for genetic testing and a review of associated podocyte gene mutations”. September 2010. Accessed 3 October 2018. ↩

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45. Nephcure Kidney International. “Diet and Nutrition”. Accessed 3 October 2018. ↩

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**What is Nephrotic Syndrome?**



**Definition**



Nephrotic syndrome is a kidney disorder characterized by the excessive loss‍ of protein in​ the urine, specifically ⁣albumin. It results ​in low levels of protein in the blood (hypoalbuminemia)‍ and abnormal fluid retention (edema).



**Causes**



Nephrotic syndrome can have several causes, including:



* **Primary (idiopathic)**: No ⁤underlying cause can be identified.

* **Secondary**: Caused by another medical condition,⁤ such⁢ as:

​ * Diabetes

* Lupus (SLE)

‌ * Amyloidosis

​ ⁢* Certain medications



**Symptoms**



* Edema (swelling in legs, ankles, feet, hands, and face)

* Foamy or bubbly ​urine

* Frequent urination at night

* Fatigue

* Loss⁢ of appetite

* Abdominal‌ pain

* Nausea and ⁤vomiting



**Diagnosis**



Nephrotic syndrome is diagnosed through:



* **Urine‍ test**: Checks for protein ‍levels in the urine (proteinuria).

* **Blood test**: Measures albumin levels and checks⁢ for ⁣other abnormalities.

* ‌**Kidney biopsy**: In some cases, a ‌small sample of kidney tissue​ may be taken to determine the cause.



**Treatment**



Treatment for nephrotic syndrome depends on the⁤ underlying cause and severity. It may ⁢include:



* **Medications** ⁢to reduce protein loss‌ in‌ the urine (corticosteroids, diuretics)

* **Immunosuppressive drugs** to suppress the immune system

* **Dietary‌ modifications**​ to ⁢reduce sodium and protein intake

* **Surgery** in severe cases​ where underlying conditions‍ need correction

* **Dialysis**⁤ or **kidney transplant**⁤ in advanced cases where kidney function is ​severely impaired



**Prognosis**



The prognosis for nephrotic syndrome varies depending on the underlying cause and severity.​ With early detection and ​appropriate ‌treatment, most patients can experience improvement in symptoms and long-term‍ kidney function. However,‍ some cases can ⁤lead to permanent kidney damage or kidney failure.



**Additional Information**



* **Types**: Nephrotic​ syndrome‌ can ⁤be classified as minimal change disease, focal segmental glomerulosclerosis (FSGS), or⁣ membranous nephropathy, based ⁢on the underlying cause of glomerular ⁣damage.

*‌ **Risk Factors**: Certain factors, such as diabetes, family history, ​and certain medications,⁢ can⁣ increase ⁢the risk of developing nephrotic syndrome.

*⁤ **Complications**:‍ Untreated nephrotic syndrome ‍can lead to ‌serious complications such as blood ⁣clots, infections, and impaired kidney function.

* **Prevention**: ​There ⁤is⁤ no known ‍way to prevent nephrotic syndrome, but early diagnosis and management⁤ can minimize complications.