Nephrotic Syndrome (Kidney Disease)

We understand that you may have a lot of questions when your child is diagnosed with nephrotic syndrome:

• What is it?
• How serious is it?
• What’s the long-term outlook for a child with nephrotic syndrome?

We’ve provided some answers to those questions here, and when you meet with our experts, we can explain your child’s condition and options fully.

Why is nephrotic syndrome a concern?

Aside from the risk of kidney damage, nephrotic syndrome carries two main risks:

• Infection—Fluid that escapes the blood and enters the tissues, as happens in edema, is susceptible to serious infection by bacteria such as E. coli.
• Blood clots—When a child loses lots of blood protein, it’s harder for his body to form blood clots in the right way. This can lead to both minor and major problems, including pulmonary embolism, in which a blood clot cuts off blood supply to the lungs.

 
What are the different types of nephrotic syndrome?

One way to categorize types of nephrotic syndrome is by what’s causing them.

Idiopathic nephrotic syndrome—the kind most children have—occurs for a reason that is unknown.

Secondary nephrotic syndrome is caused by another medical condition or treatment for another condition, such as

• diabetes
• hepatitis B and hepatitis C
• medications (such as corticosteroids)
• cancer
• lupus

It’s another way to look at nephrotic syndrome is in terms of how the affected tissue appears under a microscope, since this often correlates with treatment and outcome. There are two main categories: minimal change disease (MCD) and focal sclerosis (FSGS).

Minimal change disease (MCD) is so named because if you were to look at a kidney biopsy under a microscope, you’d see that the cells look relatively normal, and only have minimal changes. MCD:

• affects between 85 and 95 percent of children with NS in the United States
• is generally associated with the most positive outcomes among children with NS
• usually responds to steroids
• tends to relapse less and less frequently as the child grows older
• is often outgrown by the time the child is a young adult
• usually doesn’t affect kidney function
• rarely results in a child needing dialysis or kidney transplant

Focal sclerosis (FSGS)

Focal sclerosis:

• affects around 10 percent of children with NS in the United States
• tends to be a more aggressive form of nephrotic syndrome
• usually doesn’t respond to steroid therapy
• may require multiple biopsies to diagnose
• appears to disproportionately affect African-American and Hispanic populations in the U.S.
• often result in the child needing kidney dialysis and/or kidney transplant

Researchers aren’t yet sure whether MCD and FSGS lie on an opposite ends of a continuum of the same disease, or are, in fact, fundamentally different diseases.

Congenital nephrotic syndrome

What is congenital nephrotic syndrome?

While “congenital” means present at birth, congenital nephrotic syndrome is usually discovered when a baby is a few months old, although it may take up to a year. Babies with congenital nephrotic syndrome show the same kinds of symptoms as children with nephrotic symptoms.

How common is it?

Congenital nephrotic syndrome is extremely rare. Less than one percent of children with nephrotic syndrome have this type.

Can it be diagnosed before birth?

While there’s no prenatal test for congenital nephrotic syndrome, information gained from other prenatal tests can provide clues as to whether the fetus might be leaking protein in his urine. So prenatal testing can give indicate that a child might have the condition, but it’s not conclusive.
What causes congenital nephrotic syndrome?

Congenital nephrotic syndrome may be caused by a genetic abnormality in one or more proteins and your baby’s doctors usually screen for them. It probably won’t change the treatment that your child receives, but it may suggest genetic counseling and prenatal screening in future pregnancies. It may also give doctors a clue as to how quickly your child will need a kidney transplantation

Much more rarely, congenital nephrotic syndrome may result if a pregnant mother has an infection that’s transmitted to her baby, such as herpes, toxoplasmosis, or syphilis. In these cases, treating the infection usually treats the nephrotic syndrome, too.

Is congenital nephrotic syndrome serious?

Most forms of congenital nephrotic syndrome are aggressive and require significant medical intervention. It’s not uncommon that babies born with congenital nephrotic syndrome require a kidney transplant within the first few years of life, and many babies need one even sooner.

What is the outlook for a baby with congenital nephrotic syndrome?

Babies with congenital nephrotic syndrome need blood protein infusions, often every day, through an IV. Some children come into the hospital for this treatment, and some can receive infusions at home. They may also need hormones and boosters to their immune systems to keep their bodies healthy until they’re about six months old.

Then, doctors usually operate to remove the child’s kidneys. Without kidneys, the problems caused by leaking protein are gone, but the child’s body still needs to have done what the kidneys were doing. So the baby’s healthcare team will put him on dialysis while awaiting a transplant. This usually happens when a child weighs about 15 lbs., which is usually when he’s around 1 year old.

Here at Children’s, our specialists have lots of experience caring for babies with congenital nephrotic syndrome, seeing them through dialysis and kidney transplantation. In fact, we’re able to perform transplants on smaller babies than many other centers, so children we treat don’t have to wait as long to get their new kidneys.

Causes

What causes nephrotic syndrome in children?
Most children have idiopathic nephrotic syndrome, which means that there is no clear cause. Researchers have identified a few genetic associations, but not strongly enough that it can be characterized as a genetic syndrome. In other parts of the world, where children are more likely to be affected by focal sclerosis (FSGS) than by minimal change disease (MCD), FSGS seems to have more clearly defined genetic causes.

In rare cases, nephrotic syndrome may develop from a viral disease, such a hepatitis or HIV, and relapses may also be triggered by viruses. Certain medications may cause nephrotic syndrome, too.
Signs and symptoms

What are the signs and symptoms of nephrotic syndrome in children?

Signs of nephrotic syndrome may vary significantly from child to child, but you or your child may notice:

• fatigue and malaise
• decreased appetite
• weight gain and facial swelling
• abdominal swelling or pain
• foamy urine
• edema (fluid accumulation in the body spaces)
• pale fingernail beds
• dull hair
• ears cartilage may feel less firm
• food intolerances or allergies

FAQ

Q: Can nephrotic syndrome be cured?

A: The vast majority of kids in the United States with nephrotic syndrome outgrow it by the time they reach early adulthood. Until that time, they may experience relapses, but these can most often be anticipated and quickly brought under control with medication. A smaller percentage have a more aggressive form of the syndrome, and may require lifelong medical follow-up.

Q: What’s the long-term outlook for a child with nephrotic syndrome?

A: For between 85 and 90 percent of kids with nephrotic syndrome—those with minimal change disease—the outlook is quite good. Their nephrotic syndrome can be brought under control with steroids. Relapses are common, but they can be brought into remission with medication, and kids with this type of NS usually outgrow it by early adulthood.

If your child has focal sclerosis (FSGS), nephrotic syndrome is harder to treat. It often doesn’t respond to steroids, and in about 50 percent of children, FSGS may progress to end-stage renal disease. When this happens, dialysis or kidney transplantation can be an option.

Q: Are my other children more at risk for nephrotic syndrome?

A:Probably not. There do seem to be some types of FSGS that run in families, but in the vast majority of cases, only one child in a family is affected by nephrotic syndrome.

Q: Should my child stay away from certain physical activities?

A:Most likely not, but your child’s doctor will be able to tell you for sure. Here at Children’s, we recommend that children continue to go to school and participate in normal activities. If your child is taking high doses of steroids or other medicines that suppress her immune system, it’s important to try to avoid exposing her to someone who is ill.
Questions to ask your doctor

After your child is diagnosed with nephrotic syndrome, you may feel overwhelmed with information. It can be easy to lose track of the questions that occur to you.

Lots of parents find it helpful to jot down questions as they arise–that way, when you talk to your child’s doctors, you can be sure that all of your concerns are addressed. If your child is old enough, you might encourage him to write down questions as well.

Here are some questions to get you started:

• How did you arrive at this diagnosis?
• What does this diagnosis mean for my child’s kidneys?
• Are there any other conditions my child might have in addition to nephrotic syndrome?
• What might be causing my child’s nephrotic syndrome?
• How did you come to that conclusion?
• What treatment is best for my child right now, and why?
• What kind of improvement should I be noticing, and how soon?
• Are any restrictions or changes in exercise, diet or other daily activities necessary?
• When and how will you follow up with my child?
• What resources are available to help my family cope?
• Is there anything else I should know right now?

How do we diagnose NS?

The first step in treating your child is forming an accurate and complete diagnosis. The process usually starts when a child goes to his pediatrician’s office or even to an emergency room because his body is suddenly very swollen. Since that’s a well-known sign of nephrotic syndrome, your child’s doctors will perform diagnostic tests to check for high levels of protein in his urine and low levels of protein in his blood.

Your child’s doctors will also examine his urine under a microscope for signs of kidney inflammation. If they don’t see a lot of kidney inflammation, there’s a good chance that he has minimal change disease.

Doctors will most likely test your child for tuberculosis (TB) because steroids (a common treatment for NS) can reactivate TB and make it spread throughout your child’s body.

Within a few days of diagnosis, your child will most likely start on a course of steroid treatment. Many children are treated for about eight weeks, although some respond much more quickly — to see if they’ll respond to the steroids. If your child hasn’t responded to the steroids, his doctors may order a biopsy to check to see if the nephrotic syndrome may be caused by focal sclerosis (FSGS).

It’s important to remember that the doctor will be looking at very small amounts of tissue to examine the tiny filtering units. He or she may only be able to see 20 to 30 filtering units. Since in FSGS, not all of the filtering units are affected, it may look like a child doesn’t have FSGS, simply because the biopsy only picked up filtering units that aren’t affected. If your child’s doctor suspects that your child may have FSGS, he or she may ask for additional biopsies to make sure that your child is getting the proper treatment.

Your child’s doctor may also order a biopsy if your child is experiencing bad side effects from steroid therapy. The biopsy can provide information about which medicines may be more helpful.

After we complete all necessary tests, our experts meet to review and discuss what they have learned about your child's condition. Then we will meet with you and your family to discuss the results and outline the best treatment options.

How do we treat nephrotic syndrome?

Since assessing how well your child responds to treatment is part of the diagnostic process, your child is given a course of steroid therapy to see whether his nephrotic syndrome clears up. While it can take up to eight weeks for the steroids to work, many children respond within a month.

If your child doesn’t respond to steroid therapy, that doesn’t necessarily mean that he has focal sclerosis (FSGS). His doctor may order a biopsy to try to learn whether it could be FSGS, and which paths of treatment are likely to be the most beneficial. His doctor will likely also prescribe different medications.

If your child’s NS responds to the new medication(s), and his doctors suspect that he has minimal change disease (MCD) his doctors will use the medication to treat the NS until it goes into remission.

If your child has FSGS and responds to new medication(s), it’s likely that your child will never be taken off of the medication, since he is considered to be much more likely to relapse.

In some children, their FSGS loses its response to therapy. This means that:

• Their FSGS may have responded to steroids at first (and doctors may have thought that it was MCD), but then steroids don’t help when a relapse comes on. In this case, your child’s doctor may order a biopsy to look for signs of FSGS.
• Medication may appear to keep FSGS under control at first, but lose its effectiveness over time.

If your child’s FSGS progresses to end-stage renal disease, your child may need dialysis and/or a kidney transplantation.

What’s the long-term outlook for children with nephrotic syndrome?

Long-term outlook depends on the child and what’s behind his nephrotic syndrome. While each child is different, there is some data that can help give you an idea:

If your child has minimal change disease:

• Under 20 percent — around one in six or seven children — won’t experience another episode (relapse) and be “cured” after their initial treatment with steroids. But most children will relapse. We expect this, and can help you monitor for it and then treat it when it occurs.

• Around 30 percent of kids with NS are “frequently relapsing,” meaning that they’ll have three or four more relapses within a year.

• Another 30 percent of kids will be “steroid dependent,” meaning that they’ll need to continually use steroids to manage their nephrotic syndrome throughout their lives.

Relapses are especially common for the first few years after the child is diagnosed. If your child experiences a relapse, his doctors will balance his use of steroids to achieve the best results with minimal side effects.

If your child has focal sclerosis:

• Up to 20 percent or so will respond to therapy and go into remission.

• Around 30 percent of kids have some degree of response to steroids and/or other medication. They may have high blood pressure and some kidney problems, but not reach the point where they need kidney dialysis and/or a transplant.

• Around half of kids will not respond to medication and develop end-stage renal disease. These children will need kidney dialysis and/or a kidney transplant.

• Around 40 to 50 percent of children with FSGS who have had a kidney transplant experience FSGS in the new kidney, too. At Children’s, we have a protocol that lowers this number to around 20-25 percent.

How will I know if my child is responding to steroid treatment?

Here at Boston Children’s, we’ll teach you how to test your child’s urine protein levels at home. As your child begins to respond to the steroids, there will be less and less protein in his urine, and we’ll be able to wean him off of steroids.

How will I know if my child is relapsing?

If your child has been doing well but the at-home tests show a protein level of 2+ or more for more than three days in a row, please call your child’s doctor.

While your child is relapsing, make sure that he’s careful with how much salt and fluids he takes in. Once your child has responded to treatment for his relapse, the restrictions on salt and fluid can be eased.

How Boston Children’s Hospital cares for nephrotic syndrome

With about 3,200 patient visits annually, the General Renal Program at Boston Children's evaluates and treats children with nephrotic syndrome and acute kidney injury or chronic kidney disease as well as fluid, electrolyte, or metabolic abnormalities. We are part of the Division of Nephrology, the largest pediatric nephrology service in the United States.

Our division includes a pediatric dialysis unit with special expertise in:

• acute and chronic hemodialysis
• peritoneal dialysis
• continuous renal replacement therapy

In addition to providing expert care today, we’re searching for ways to improve the lives of children with nephrotic syndrome tomorrow by conducting research to better understand the disease and find new treatments.

Coping and support

We know how worrying a diagnosis of nephrotic syndrome can be, both for your child and for your whole family. That’s why our physicians are focused on family centered care: From your first visit, you’ll work with a team of professionals who are committed to supporting all of your family’s physical and psychosocial needs. Here are some of the ways in which we can help:

• Patient education: Our nurses will be on hand to walk you through your child’s treatment and help answer any questions you may have—Are my child’s treatments working? What do we do next? They will also reach out to you by phone, continuing the care and support you received while at Boston Children’s.

• Parent to parent: Want to talk with someone whose child has been diagnosed with nephrotic syndrome? We may be able to put you in touch with other families who can share their experience.

• Faith-based support: If you are in need of spiritual support, we will help connect you with the Boston Children’s Department of Spiritual Care (chaplaincy). Our program includes nearly a dozen clergy representing Episcopal, Jewish, Lutheran, Muslim, Roman Catholic, Unitarian and United Church of Christ traditions who will listen to you, pray with you and help you observe your own faith practices during your hospital experience.

• Social work and mental health professionals: Our social workers and mental health clinicians have helped many other families in your situation. We can offer counseling and assistance with issues such as coping with your child’s diagnosis, stresses relating to coping with illness and dealing with financial difficulties.

On our For Patients and Families site, you can read all you need to know about:

• getting to Boston Children’s
• accommodations
• navigating the hospital experience
• resources that are available for your family

Our Division of Nephrology is dedicated to better understanding and developing lasting treatments for the most serious kidney diseases affecting children. Some of our initiatives have focused on FSGS.

Reducing the recurrence of FSGS after transplant

FSGS tends to return in 50 percent of kidney transplants, often recurring in the immediate post-transplant period and causing transplant loss. Using apheresis as part of a pre-transplant conditioning protocol, the Boston Children's Hospital Nephrology team led by Michael Somers, MD, has reduced the typical FSGS recurrence rate by more than half and has successfully reversed most FSGS in children who did recur.

Gene for FSGS discovered

Researchers from Boston Children's and Brigham and Women's Hospital have identified an important genetic cause of a devastating kidney disease that is the second leading cause of kidney failure in children. The study may provide clues to developing treatments for the disease, FSGS, which currently forces children and young adults onto dialysis and often requires a kidney transplant. No effective treatments are known, and years of research have failed to uncover the underlying disease mechanism.