Nephritic Syndrome

Nephritic syndrome is the name given to a collection of different signs and symptoms that occur as a result of inflammation in the kidneys. This inflammation causes the kidneys to work less effectively. It also causes protein and red blood cells to leak from the bloodstream into the urine.

There are many conditions that may cause nephritic syndrome, and it can occur in people of all ages. Common causes are infections, immune system disorders and inflammation of the blood vessels. The main symptoms are passing less urine than normal, leading to a fluid buildup in the body, and having blood in the urine. People with nephritic syndrome also often develop high blood pressure.

Treatment depends on the underlying cause, but usually involves managing the high blood pressure and reducing the inflammation in the kidneys. Although many people recover well from nephritic syndrome, some people may go on to develop renal failure. The risk of renal failure depends on the severity of the syndrome and its underlying cause.

Nephritic syndrome is not a disease but a syndrome. A syndrome is a group of symptoms that often and predictably occur together, and which develop as a result of another condition. Syndromes are not necessarily specific to any disease or disorder. Nephritic syndrome has many potential triggers, therefore, successfully treating it involves identifying the underlying cause. 1

Nephritic syndrome has both acute and chronic forms. Acute, or rapidly-progressing, nephritic syndrome usually comes on suddenly and, because of acute and painful symptoms, seldom goes undetected. Chronic nephritic syndrome typically progresses slowly and often goes undetected for some time. 2

Chronic inflammation of the kidneys can cause scarring, which may negatively impact kidney function and lead to high blood pressure and, eventually, if left undiagnosed and untreated, to a need for dialysis (renal replacement therapy, when a dialysis machine replaces the kidneys’ function and filters waste products from the blood), and possibly kidney transplantation. 3

Nephritic syndrome is the result of inflammation affecting small groups of blood vessels, known as glomeruli, in the kidneys. As the glomeruli are the kidneys’ main filter units, this inflammation disrupts the kidneys’ ability to adequately filter blood. The inflammation can originate in the kidneys themselves or be the result of infection or injury elsewhere in the body. 2 It can occur in people of any age, including children.

Nephritic syndrome can develop as a result of any of the following: 1 4

Primary glomerular diseases: Such as IgA nephropathy (Berger’s disease) or membranoproliferative glomerulonephritis. IgA nephropathy is a very common cause of nephritic syndrome. 5

Bacterial infections: Such as methicillin-resistant staphylococcus aureus (MRSA), pneumococcal pneumonia, typhoid, infective endocarditis, or secondary syphilis. Nephritic syndrome following a streptococcal throat infection is fairly common, especially in children.

Viral infections: Such as hepatitis B, mumps, measles, chickenpox or glandular fever (mononucleosis).

Multisystem systemic/inflammatory diseases: Such as vasculitis, Goodpasture’s Syndrome, granulomatosis with polyangiitis, Henoch-Schönlein purpura, or lupus (systemic lupus erythematosus).

Abdominal abscess: A pocket of infected fluid and pus inside the abdominal cavity. This can be located on or near any organ.

Parasitic infections: Such as malaria.

As there are many underlying conditions for nephritic syndrome, there are different risk factors, such as recent infections, immune system disorders and genetic disorders. See the sections below for more information on the relationship between nephritic syndrome and glomerulonephritis, and nephritic syndrome and systemic lupus erythematosus. If you are concerned that you or someone you know may be experiencing nephritic syndrome, you can do a free symptom assessment using the Ada app at any time.

Typical symptoms include passing less urine than normal, having blood in the urine and swelling of the feet or face (edema). Other possible symptoms are flank pain, back pain, headache, shortness of breath and symptoms related to the underlying cause, for example a skin rash and joint pain.

The symptoms of nephritic syndrome differ, depending on whether the acute or chronic form of the syndrome is present.

Symptoms of acute nephritic syndrome include: 1 2 4

• Edema in the face and legs: Edema is the accumulation of fluids in the body, usually under the skin, leading to a puffy appearance.
• Low urine volume: Known as oliguria, this is defined as less than 500ml of urine being produced in a 24-hour period.
• Hematuria: Blood in the urine which often, but not necessarily, leads to red discoloration. There are two types of hematuria: microhematuria, which indicates unseen blood, and macrohematuria, in which the blood is visible to the eye.
• High blood pressure: Hypertension, which results from the disruption of kidney function, may also occur. High blood pressure is generally defined as a resting blood pressure of 140/90 mmHg or higher in adults, 6. In children, what constitutes hypertension depends on the age and size of the child.
• Fever, weakness and fatigue
• Appetite loss, vomiting and abdominal pain
• Malaise (a feeling of general unwellness) and nausea may also be present.

Chronic nephritic syndrome usually presents with fairly mild or even undetectable symptoms, which can include: 2

• Edema
• Hypertension/high blood pressure
• Kidney failure in later stages

Symptoms of kidney failure can include:

• Itchy skin and/or rash
• Decreased appetite
• Nausea
• Vomiting
• Fatigue
• Difficulty breathing

In both chronic and acute nephritic syndrome, the urine will usually contain high concentrations of red blood cells, as the blood cells leak out of the damaged glomeruli. If you are concerned that you or someone you love may have nephritic syndrome, you can consult the Ada app for a free symptom assessment.

The diagnosis of nephritic syndrome is typically based on a physical examination of the person and analysis of their urine (urinalysis). People with nephritic syndrome tend to have high blood pressure, so a doctor will check this. A doctor will also look for signs of:

• Abnormalities, such as dark color or cloudiness in the urine
• Protein in the urine (proteinuria), which may indicate nephrotic syndrome
• Uremia, an excess of urea or creatinine in the blood, or azotemia, an excess of nitrogen-rich waste compounds in the blood
• Increased fluid volume in the body, which may lead to edema
• Reduced filtration in the kidneys, specifically the glomeruli

A kidney biopsy (tissue sample from the kidney) may be performed to investigate the cause of the nephritic syndrome.

Because nephritic syndrome is a cluster of symptoms rather than a disease in itself, much of the testing that makes up the diagnosis is aimed at determining what the underlying cause is. Another important element in diagnosis is differential diagnosis, as the illness may be nephrosis rather than nephritis.

In examining a person with potential nephritic syndrome, a doctor might carry out the following tests: 1

Take patient history: A doctor will ask the affected person about the time at which their symptoms began and attempt to determine the point at which the kidneys began to excrete protein into the urine.

Check appearance and colour of urine: Urine that is dark in colour may be very concentrated and contain blood.

Blood pressure: Hypertension can be a sign of disrupted kidney function.

Edema assessment: Edema, or fluid gathering in the tissues, can be a sign that there is not enough protein in the blood and may suggest proteinuria.

Urine dipstick test: A simple form of urinalysis that is used as a quick test for blood and protein in the urine. They will use a dipstick test, in which a test-strip of paper is immersed in a urine sample, to check for blood and protein in the urine

Urinalysis: A urine sample will be sent to a laboratory to do a precise check for protein levels and red blood cells.

Blood tests: To check levels of electrolytes, creatinine, blood urea nitrogen, immunoglobulins, antibodies, and other substances.

Kidney biopsy: This relatively straightforward procedure may be performed as an outpatient procedure or after hospital admission, depending on the patient’s particular circumstances. It uses only local anesthetic and is done using ultrasound and specialized biopsy needles to remove a small sample of tissue. Kidney biopsies are a very reliable way of distinguishing chronic glomerulonephritis from other, similar, disorders. 2

Treatment depends on the underlying causes. Medications (such as ramipril, benazepril, candesartan, or valsartan) are typically used to treat the high blood pressure. Medications will also be administered to reduce inflammation in the kidneys.

Generally, doctors will recommend: 1

• Bed rest
• A diet that is restricted in salt, potassium and fluid
• Medication to control blood pressure, if necessary
• Medication to reduce inflammation
• Medication to remove fluids from the body
• Dialysis to replace kidney function in severe cases

The time it takes to recover from nephritic syndrome varies according to its severity and the underlying cause. Most patients begin to feel better fairly soon, especially if treatment is prompt.

Kidney disorders are complex and may not be entirely distinguishable from one another without extensive testing. The terminology can also be hard to grasp. Some associated conditions include: 2 7

• Nephrotic syndrome
• Acute nephritis
• Acute glomerulonephritis
• Rapidly-progressive glomerulonephritis
• Chronic glomerular disease
• Lupus nephritis

Both nephritis and nephrosis are among the body’s responses to injury or illness affecting the kidneys. Nephrotic syndrome is characterized by severe proteinuria, i.e. high amounts of protein, including albumin, in the urine, while nephritic syndrome’s major feature is inflammation. Depending on the specific underlying conditions of the two, nephrotic syndrome often is the more serious. 8 In both cases, medical care should be sought as a matter of urgency. Doctors will usually need to order tests to determine whether a patient has nephritic or nephrotic syndrome. ref8 7 9

Glomerulonephritis refers to a number of kidney problems that involve inflammation in the glomeruli, which are the kidney’s filtration units. Acute glomerulonephritis can cause nephritic syndrome. Glomerulonephritis can be acute (sudden onset, lasting for a short time) or chronic (long-lasting), and it can result from a variety of factors, such as: 10

• Infections, especially those involving streptococcal bacteria
• Autoimmune conditions, such as systemic lupus erythematosus (see below)
• Hereditary factors

Edema, hematuria and hypertension are known as the nephritic triad.

Acute poststreptococcal glomerulonephritis (APSGN) generally, and rapidly-progressive glomerulonephritis (RPG) occasionally result from infections. 11 12

The symptoms of acute glomerulonephritis resemble those of acute nephritic syndrome, and include: 13 14

• Edema, often showing first as facial puffiness in the morning
• Hematuria: blood in the urine, which can color it pink, red or brown
• Oliguria: producing less urine than usual
• Hypertension: high blood pressure
• Fatigue: feeling tired, weak and/or exhausted (almost) constantly

Edema can also cause shortness of breath and coughing. If you are concerned that you or someone you know may be experiencing nephritic syndrome, you can do a free symptom assessment using the Ada app at any time.

Post-infectious glomerulonephritis is a common cause of acute glomerulonephritis, especially among children. It can be caused by a wide range of conditions and factors, including viral infections such as Epstein-Barr virus infection, the flu or Hepatitis B, and bacterial infections such as staphylococcal, pneumococcal and streptococcal infections. It commonly occurs after streptococcal infections. 15

Some conditions that can increase a person’s risk of developing post-infectious glomerulonephritis are for example: 11 15

• Sore throat, usually pharyngitis (cobblestone throat)
• Skin infections
• Diabetes
• Alcoholism
• Malignancies such as cancer or leukemia
• Heart-valve replacement surgery
• HIV infection
• Intravenous drug use

In acute postinfectious glomerulonephritis, the symptoms typically appear some weeks after the infection that triggered it has cleared up. This is typically within one to two weeks after pharyngitis or up to a month after a skin infection. If symptoms appear within a few days, however, it is possible that there are existing renal problems. 11

Symptoms of acute postinfectious glomerulonephritis include the nephritic triad: 12 13 14

• Hematuria, causing red, pink, brown or cola-colored urine
• Edema, causing facial puffiness and swelling in the legs and arms
• Hypertension, or high blood pressure

Oliguria, or reduced urine output, is less common, occurring in less than half of cases. Urinalysis can confirm hematuria even if no blood is visible in the urine; in this case it is called microscopic hematuria.

Acute poststreptococcal glomerulonephritis (APSGN) usually follows an infection, typically a streptococcal infection of the throat or skin, but also may result from mild infections that follow other illnesses or surgical procedures. APSGN is a post-infectious glomerulonephritis.

Acute poststreptococcal glomerulonephritis is most commonly found among children between the ages of four and 12, although it is also becoming more common among people who are older than 50. 14 It is more common among men than women.

The prognosis for children with acute postinfectious glomerulonephritis is good, though it can be less positive for older people. Certain debilitating conditions may also cause the prognosis to be more serious. These include:

• Malnutrition
• Alcoholism
• Diabetes
• Chronic illnesses
• HIV infection
• Intravenous drug use
• Cancer

If symptoms are severe or one of the above risk factors is present, a nephrologist or pediatric nephrologist may need to be consulted additionally to a GP.

Because the condition is generally already healing by the time symptoms become apparent, this form of glomerulonephritis is usually treated by managing the symptoms and supporting recovery. This includes managing the edema and hypertension, and supporting kidney function. Any medication that is administered will be aimed at reducing hypertension and helping kidney function to return to usual. (See the section on treatment of nephritic syndrome above for more information.)

Good to know: Rapidly-progressive glomerulonephritis (RPGN) is another form of post-infectious glomerulonephritis, but it may also occur for reasons not connected to an infection; post-infection RPGN is only one type of RPGN. Post-infection RPGN often occurs in the month following a bout of flu-like symptoms. The exact symptoms of rapidly-progressive glomerulonephritis depend on what underlying condition causes it, but may include: 12 16

• Weakness
• Fatigue
• Fever
• Nausea and vomiting
• Appetite loss and therefore unintended weight loss
• Joint pain
• Muscle pain
• Painful skin lesions
• Abdominal pain
• Nausea and vomiting
• Edema
• Low urine production

Treatment for rapidly-progressive glomerulonephritis must be sought as quickly as possible. The disorder can cause damage before it becomes symptomatic, so the long-term prognosis depends on a rapid response once symptoms are apparent.

Rarely, a case of rapidly-progressive glomerulonephritis involving the lungs may occur. This is called pulmonary-renal syndrome. People with this condition may also, in addition to having the above-mentioned renal symptoms, cough up blood. This combination of coughing up blood and renal symptoms is an emergency that may lead to kidney and lung failure. Urgent medical treatment should be sought without delay. If you are concerned that you or a loved one may have a post-infection kidney problem, consult the Ada app for a free symptom assessment.

Systemic lupus erythematosus, often known simply as lupus, is an autoimmune disease that can affect any of the body’s systems. 17 Lupus mostly affects women. Lupus affecting the kidneys is known as lupus nephritis, a kind of inflammation of the kidneys. About half of all people with lupus are affected by lupus nephritis. In children with lupus, about eight out of ten will have lupus nephritis. 18

In lupus nephritis, inflammation inside the kidney causes glomerulonephritis and therefore nephritic syndrome. 19 In the early stages of this disorder and sometimes even later, there may be no symptoms of anything being wrong with the kidneys, although lupus nephritis may be diagnosed using urine tests and kidney biopsy at any time. 17 Lab tests in people with lupus nephritis show proteinuria and hematuria, even if they are asymptomatic.

Symptoms of lupus nephritis include: 18 20 19

• Edema: puffiness or swelling in the feet, ankles, legs, hands, face and eyelids
• Foamy or red, brown, or pink urine
• Weight gain
• Joint pain or swelling in the joints
• Headache
• Dizziness
• Blood clotting problems
• Hypertension (high blood pressure)

Foamy urine is a sign of proteinuria, or protein in the urine. Pink, red or brown urine is a sign of hematuria, i.e. blood in the urine. Muscle pain and a butterfly rash on the face may also occur, but these are general symptoms of lupus and not specific to lupus nephritis. For more information, see this resource on lupus.

Good to know: Lupus itself often affects the kidneys, but does not cause kidney infections in the same way that something like a urinary tract infection may. While lupus nephritis is not itself a kidney infection, meaning it is not caused by bacteria, viruses or other infectious causes, medications used to treat lupus can suppress the immune system, potentially leading to an increased risk of infections of the kidneys. 19

If you are concerned that you or a loved one may have lupus or a kidney problem, consult the Ada app for a free symptom assessment.

Diagnosis of lupus nephritis involves urine and blood tests and often a kidney biopsy. Urine tests are used to measure the levels of protein, red blood cells and creatinine in the urine. High levels of creatinine indicate that the kidneys are not filtering wastes out of the blood very well. The same is true of high levels of protein in the urine. High levels of protein in the urine also may indicate that nephrotic syndrome is present. 18 A blood urea nitrogen, or BUN, test may also be done using a blood sample taken from a vein. This test will also be an indication of how compromised the filtering capabilities of the kidneys are. 21 A kidney biopsy, which is an outpatient procedure, will confirm the presence of lupus nephritis and determine how badly the kidneys are affected. In a kidney biopsy, a needle is used to take a small sample of kidney tissue, which will be sent to a laboratory for analysis.

Lupus nephritis is usually treated using medication to reduce inflammation, decrease the severity of the body’s auto-immune response and prevent the body from attacking the kidneys. Commonly-used medications include: 22 23

• Corticosteroids
• Hydroxychloroquine
• Cyclophosphamide
• Mycophenolic acid
• Azathioprine

Managing the hypertension that accompanies nephritic syndrome in glomerulonephritis also requires medication, which can include: 18 24

• ACE inhibitors
• Other Diuretics
• Beta-blockers
• Calcium-channel blockers

The goal of treatment for lupus nephritis is to support kidney function and keep it as normal as possible, while preventing it from becoming worse. 20

Treatment for lupus nephritis works well, so the prognosis is generally good. However, lupus nephritis can cause kidney function to decline as time goes by, and between 10-30 percent of people with lupus nephritis may develop kidney failure. 18 Very severe lupus nephritis may cause diffuse proliferative nephritis, which causes scarring to accumulate in the kidneys. This scarring causes kidney function to decline or, in the worst case, even fail.

Q: Is nephritic syndrome dangerous during pregnancy?
A: Nephritic syndrome indicates a problem with the kidneys, which is of great concern for pregnant people, whose kidneys and other internal organs are already adapting to pregnancy and thus under increased demand. A doctor should be consulted without delay if symptoms occur. Acute nephritic syndrome poses certain health risks to both mother and baby. Chronic nephritic syndrome, though rarer, is also of concern. If nephrotic syndrome occurs, complications for both mother and baby may occur, even if renal function isn’t badly affected. Mothers may experience postnatal problems, such as edema, urinary tract infections and anemia. 26 A doctor should be consulted as soon as possible.

Q: Can I take painkillers if I have or have had nephritic syndrome?
A: There is some evidence that non-steroidal anti-inflammatory drugs (NSAIDS) can worsen existing kidney damage or lead to kidney damage if used in high amounts exceeding the standard dosages over time. Normal dosages, when taken only as directed, are safe. 27 NSAIDs include diclofenac , celecoxib, etoricoxib, indometacin, ibuprofen, ketoprofen, high-dose aspirin (above 300mg per dose), mefenamic acid, and naproxen. 28 High doses of NSAIDs over time can lead to chronic interstitial nephritis. Patients with kidney problems should use NSAIDs only under the direct supervision of a doctor.

Opioids such as morphine, hydrocodone or oxycodone, should generally be avoided, except in post-surgical or severe long-term pain, and would not ordinarily be prescribed by physicians due to their addictive properties.

Acetaminophen, also known as paracetamol, is generally a safe painkiller for use by people with kidney problems or suspected kidney problems. However, overuse of acetaminophen can lead to liver damage. Acetaminophen reduces pain and fever, but is not an anti-inflammatory. 29

However, all patients should consult a doctor before taking NSAIDs or any other painkillers.