Nephrotic Syndrome of Childhood: A Common Rare Disorder
Nephrotic syndrome (NS) fulfills the criteria for an oxymoron. As a pediatric nephrologist, I consider it a routine, common disorder. The general public sees it as rare, given that only 4-8 children per 100,000 develop this problem.
NS can be thought of as a disorder of leaky kidneys. Normal glomerular capillaries filter out the watery portion of the blood, leaving the protein and cells behind in the capillary. If something happens to the “slits” through which this filtration occurs, protein (and sometimes cells) can enter the filtrate and end up in the urine.
The most obvious consequence of loss of protein is swelling. Protein in the blood helps keep water in the blood vessels. Blood protein levels fall when the kidney leaks this way, and water can seep out of the blood vessels. The face, especially the area around the eyes, may swell. Fluid in the belly, called ascites, may flatten the belly-button. Boys often have swollen genitals. After being upright for a few hours, the swelling (or edema in doctor talk) may drain from the face, into the legs.
Proteins lost in the urine may produce other complications. Proteins involved in immunity are lost, increasing the child’s risk of infections. The proteins that prevent blood clotting also get wasted, increasing the risk of dangerous clots. In response to these losses, cholesterol and other fats in the blood can increase.
In most children, NS is idiopathic, meaning we do not know its cause. NS can be secondary to a number of diseases, including some cancers, infections, and vasculitis disorders (such as lupus). If NS begins before the child’s first birthday, we often find a genetic disorder in one of the proteins that makes up the filtration slits in the kidneys. Some of these mutations, in less full-blown forms, may contribute to NS later in life as well.
NS requires significant proteinuria and low blood protein levels. Doctors will perform a medical history and physical examination to look for possible secondary causes of NS and to assess the amount of swelling. Some nephrologists will examine the kidneys with ultrasound. All should get some basic laboratory studies: a complete blood count; a metabolic profile including creatinine, protein, and albumin; and levels of complements (immune system proteins which may be reduced in some complex kidney problems).
If the blood creatinine level is normal and complement levels are not low, most children will receive a course of steroids. These drugs do not make children muscle-bound; these are glucocorticoids that suppress the immune system. The initial course consists of daily medication for 4 to 6 weeks. Most children respond to this treatment within the first 2 weeks. They will then receive another few weeks of steroids every other day with a gradually tapering dose. These steroid-sensitive children may suffer more episodes of NS, often triggered by colds or other infections. Most sensitive patients eventually “outgrow” the disorder, usuallly in 2 to 5 years.
Some children respond to the initial course of steroids, but relapse shortly after the drugs are discontinued. These patients may be steroid-dependent or frequent relapsers. For these children, the long-term side effects of the steroids can be problematic, so other drugs are often used to induce longer remissions. These drugs include the chemotherapy agent cyclophosphamide, anti-rejection drugs cyclosporine, tacrolimus, and mycophenolate, and the antibody rituximab.
Some children do not respond to the steroids; they are steroid-resistant. Most nephrologists will perform a kidney biopsy on children with steroid-dependent or -resistant nephrotic syndrome. Genetic testing may also be performed to look for mutations in the filtration slit proteins. Steroid-resistant children are much more likely to have focal sclerosis or other lesions of NS that tend to progress to kidney failure over time.
Most children with NS respond to steroids and do not develop kidney failure. Even though the long-term prognosis is excellent, this disorder can be a frustrating series of relapses for several years. If you want to learn more about NS and connect with other affected families, the NephCure Foundation has a great site.