What is nephrotic syndrome? Causes, symptoms, and treatments

There are many diseases that correlate with poor kidney function. If you start noticing that your ankles are swelling, you’re nauseous, or having trouble sleeping—it can be difficult to pinpoint why your body isn’t working at it’s best. These are just a few signs of kidney damage, and there are many possible causes. Nephrotic syndrome is just one of them. What is nephrotic syndrome? Read on to learn the causes, symptoms, and treatments.

What is nephrotic syndrome?

Nephrotic syndrome occurs when your kidney’s filtering system isn’t working as well as it should. This kidney damage allows protein normally found in your blood plasma to spill into urine. The result is too much protein in your urine (proteinuria) and too little protein in your blood. The loss of protein from the bloodstream allows fluid that the protein usually holds in place to leak into the body, causing swelling (also known as edema). 

It’s a fairly rare condition that affects just 5 per 100,000 individuals, but when it’s unmanaged, it can wreak havoc on other bodily systems. Complications of nephrotic syndrome include increased risk of blood clots, high cholesterol, high blood pressure, anemia, and susceptibility to infection. Nephrotic syndrome is autoimmune-based in certain scenarios, but not all. With appropriate treatment, the prognosis is good. When left untreated, it can become severe and cause kidney failure or death.

Causes

There are clusters of tiny blood vessels (called glomeruli) in your kidneys that filter your blood as it passes through this organ. Damage to the glomeruli is the most common cause of nephrotic syndrome. However, there are many conditions that can result in glomerular damage, including:

• Diabetic kidney disease is otherwise known as diabetic nephropathy. About a quarter of all diabetics (both Type 1 and Type 2) eventually develop a kidney disease that can damage glomeruli.
• Minimal change disease is an idiopathic syndrome, meaning the cause of abnormal function can’t be determined. It gets its name because the changes to kidneys are so minimal they are not detectable in a kidney biopsy. It’s the most common cause of nephrotic syndrome in children, responsible for more than 90% of children diagnosed. Many children outgrow minimal change disease, but some bring it into adulthood. It’s less common for adults, comprising only 10%–15% of nephrotic syndrome cases. Though the cause is often unknown, it can be triggered by viral infections, nonsteroidal anti-inflammatory drugs (NSAIDs), tumors, and other allergic reactions.
• Focal segmental glomerulosclerosis (FSGS) is a progressive disease that targets specific, segmented parts of the kidney. Of all adults with nephrotic syndrome, FSGS accounts for 40% of them. For children, FSGS accounts for 20% of cases. FSGS can be caused by sickle cell disease, infections, drug interactions, obesity, toxic substances, and (rarely) inherited abnormal genes. NBA player Alonzo Mourning famously received a kidney transplant for FSGS, prompting him to retire from the league in 2003. 
• Primary membranous nephropathy (PMN) specifically affects the kidney’s glomeruli. When enough protein filters out into the urine, patients receive a nephrotic syndrome diagnosis. It can occur in all ages, but the disease is most concentrated in individuals aged 50–60. A solid 30% of patients with PMN are able to improve their condition with no treatment whatsoever. However, another 30% have a progressive condition that will eventually require dialysis or a kidney transplant. For those without diabetes, PMN is the most common source of nephrotic syndrome in adults. It’s rare in children. PMN can be caused by autoimmune diseases, viral infections, medications, and tumors.
• Systemic lupus erythematosus (SLE) is the most common type of lupus. It is a chronic inflammatory disease that can lead to kidney damage. Other types of lupus may also be etiological of nephrotic syndrome, like lupus podocytopathy and lupus nephritis.
• Amyloidosis occurs when there is amyloid protein buildup in a patient’s organs. It’s an abnormal protein and can be formed from various combinations of proteins.

Nephrotic syndrome occurs in children and adults, but often for different reasons. Children are most likely to be diagnosed with minimal change disease. Adults most frequently have a nephrotic syndrome diagnosis stemming from diabetes.

Risk factors 

All of these diseases damage the filtering system in the body’s kidneys. Additionally, there are factors that increase risk of developing nephrotic syndrome:

• Medical diagnoses: Sickle cell disease, diabetes, cancer, and lupus all make it more likely you could develop nephrotic syndrome.
• Medications: NSAIDs, several antibiotics, and some other medications increase risk for kidney damage. Ingesting certain toxic substances can also lead to kidney damage.
• Infections: HIV, hepatitis B, hepatitis C, and malarial all increase risk for nephrotic syndrome.

Taking stock of your pre-existing conditions can help you better determine if you’re at risk for nephrotic syndrome. Additionally, determining what’s causing the damage can help healthcare providers better to treat their patients.

Symptoms

Despite the different causes, there are a handful of symptoms that can guide you toward a nephrotic syndrome diagnosis. “When you have three grams of protein in the urine, plus high cholesterol, plus swelling or edema, then that is what nephrotic syndrome is,” explains Ahmad Oussama Rifai, MD, a nephrologist and clinical hypertension specialist and founder of The Virtual Nephrologist. 

The key symptoms include:

• Edema, or swelling, especially of the ankles, feet, face, and abdomen—but can occur  elsewhere in the body
• Foamy urine caused by an excess amount of protein in urine  
• Fluid retention that causes weight gain
• Fatigue
• Loss of appetite
• High cholesterol caused by your body trying to replenish lost proteins (such as lipids or anti-clotting proteins)
• Frequent infections
• Malnutrition

When these signs are “coupled with a low serum protein level called albumin,” it’s another key indicator for nephrotic syndrome, according to Barry Gorlitsky, MD, nephrologist at Carolina Nephrology and CEO of KidneyAide.

When to call your healthcare provider

“If you notice frothy urine, like the foam from pouring a beer, and or increased swelling, it is time to see a doctor,” says Dr. Gorlitsky. When you visit a healthcare provider, your physician will likely run blood tests and urine tests (or urinalysis). 

Dr. Rifai elaborates about testing: “Urinalysis is the cheapest test in medicine in the history of mankind with the amount of information it gives you. It is literally a $0.07 test that gives you 10 pieces of information, including diabetes, protein in the urine, blood in the urine, bilirubin, liver disease, jaundice, muscle weakness.” Nephrotic syndrome is just one disease that urine tests help to detect. This test can be done at home or in the doctor’s office.

A kidney biopsy can also help to figure out the underlying cause behind your symptoms. The diagnosis can be a complicated process when a kidney biopsy doesn’t provide enough information, or results in light microscopy (when you can’t see anything of note in a normal biopsy). Then, Dr. Rafai explains a doctor might do special stains, electron microscopy, or immune microscopy. “Based on that, we will decide what is the etiology and how to treat this,” Dr. Rifai says.

If you receive a diagnosis of minimal change disease from a single biopsy, you may want to request a second biopsy from a different piece of the kidney. This is because FSGS (which is focal and segmental, as the name suggests) occurs in some parts of the kidney, but not others.

Dr. Rifai likens the kidney to a garden, which may have separate segments of bushes, flowers, and trees. He adds, “If you’re unlucky enough to take a biopsy from a normal kidney part, then you will label it as minimal change disease but it’s actually FSGS.” Because FSGS is progressive, this can prove dangerous. 

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How to manage nephrotic syndrome

Every person with nephrotic syndrome is different, but as there are many causes, there are many potential treatments. 

1. Vitamin D: This nutrient helps regulate kidney function. Nephrotic syndrome patients often use Vitamin D supplements, in addition to natural sources, to help them in their treatment.
2. Dietary changes: Physicians often recommend nutritional adjustments to reduce protein in urine and extra fluid retention. In particular, patients may go on a low-sodium diet (usually less than 1,000 mg of sodium per day) as well as reduced protein intake. It’s also a good idea to limit consumption of saturated fats.

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3. Medication: There are several types of medication that your healthcare provider may prescribe, depending on the primary causes of your symptoms. 

• Steroids to help reduce the kidneys’ glomeruli inflammation
• Immune system modulators to help correct underlying metabolic problems, such as lupus or diabetes medications
• Angiotensin-converting enzyme (ACE) inhibitors to reduce high blood pressure
• Diuretics, or water pills, to reduce fluid retention and swelling
• Blood thinners, or anticoagulants, to reduce the risk of clotting

There are only a few drugs meant specifically for nephrotic syndrome. Most of these medications are used off-label to alleviate symptoms of the condition.

Even when your symptoms are well-managed by diet, supplements, and medication, you must stay vigilant for symptoms in the future. Dr. Gorlitsky says, “Often we would continue to do surveillance periodically to be sure there are no flare-ups.” This gives patients and their medical team the opportunity to manage those flare-ups as they come.