Nephrotic Syndrome (Kidney Disease)

Nephrotic syndrome (NS) is the name given to a collection of kidney-related findings in your child’s body. These include:

• Proteinuria: high levels of protein in the urine (based on your child’s age and size)
• Hypoalbuminemia: low levels of protein in your child’s blood, since it’s being passed out of his body in his urine
• Edema: swelling. This happens because the proteins in your child’s blood act as a sponge to keep fluid in the blood. With fewer proteins to do this, the fluid may leak out of the blood into your child’s tissues, causing them to swell, especially around the stomach area.
• High cholesterol (blood fat) levels: low levels of protein in the blood stimulate the body to overproduce certain kinds of blood fats

While nephrotic syndrome is not a disease, it can be the first sign of disease that can damage the kidney's tiny blood-filtering unit (glomeruli) where urine is made.

• Nephrotic syndrome always affects both kidneys.
• It usually appears between the toddler and elementary school years, although it may appear later.
• There are thought to be two forms of nephrotic syndrome, minimal change disease (MCD) and focal sclerosis (FSGS). MCD is much more common in children, and likely to respond to therapy. FSGS is a more aggressive disease, and may lead to kidney damage.
• Most children with NS outgrow it by young adulthood.

Idiopathic nephrotic syndrome, the most common form, 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)
• Childhood cancer
• Lupus

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.

Congenital nephrotic syndrome is extremely rare. Less than 1 percent of children with nephrotic syndrome have this type.

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

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.

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
• Ear cartilage may feel less firm
• Food intolerances or allergies

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 as hepatitis or HIV, and relapses may also be triggered by viruses. Certain medications may cause nephrotic syndrome, too.

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.

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.

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.

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.

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. We have a protocol that lowers this number to around 20-25 percent.

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.

Our specialists have lots of experience caring for babies with congenital nephrotic syndrome, seeing them through dialysis and kidney transplantation. 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.

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.