Nephrotic syndrome is a common kidney disease characterized by heavy loss of protein in urine, low blood protein levels, high cholesterol levels and swelling. This disease can occur at any age but is seen more frequently in children compared to adults. Nephrotic syndrome is characterized by its cycle of response to treatment, manifested by gradual tapering and discontinuation of medication, treatment free period of remission and frequent relapses causing swelling. As the cycle of recovery and recurrence repeats for a long period (years), this disease is a matter of worry for both the child and the family.
The kidney works as a sieve (filter) in our body that removes waste products and extra water from blood and passes them out via the urine. The size of the holes of these filters is so small so that in normal circumstances proteins that are large in size do not pass into the urine. In nephrotic syndrome the holes of these filters become large, so protein leaks into the urine. Because of the loss of protein in urine, the level of protein in the blood falls. Reduction of protein level in blood causes swelling (the medical term for the swelling seen in these patients is edema). The severity of edema varies depending on the amount of protein lost in the urine and reduction in protein level of blood. The kidney function (i.e., the ability to filter waste products or the glomerular filtration rate), per se, is normal in most patients with nephrotic syndrome.
In over 90% of children the cause of nephrotic syndrome (called primary or idiopathic nephrotic syndrome) is not known. Primary Nephrotic Syndrome is caused by four pathological types: minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy and membranoproliferative glomerulonephritis (MPGN). Primary nephrotic syndrome is a “diagnosis of exclusion”, i.e. they are diagnosed only after secondary causes have been excluded. In less than 10 % of cases, nephrotic syndrome may be secondary to different conditions such as infection, drug exposure, malignancy, hereditary disorders or systemic diseases such as diabetes, systemic lupus erythematosus and amyloidosis.
The most common cause of nephrotic syndrome in children is minimal change disease (MCD). This disease occurs in 90 percent of cases of idiopathic nephrotic syndrome in young children (under age six) and in 65% of cases in older children.
In a typical child with minimal change disease, blood pressure is normal, red blood cells are absent in urine and the values of serum creatinine and complement 3 (C3) are normal. Of all the causes of nephrotic syndrome, minimal change disease is the least stubborn, as over 90% of the patients respond well to steroid therapy.
Possible complications of nephrotic syndrome include an increased risk of developing infections, blood clots in the veins (deep vein thrombosis), malnutrition, anemia, heart disease due to high cholesterol and triglycerides, kidney failure and different treatment-related complications.
In patients with swelling the first step is to establish a diagnosis of nephrotic syndrome. Laboratory tests should confirm (1) heavy loss of protein in the urine, (2) low blood protein levels, and (3) high cholesterol levels.
Once the diagnosis of nephrotic syndrome has been established, additional tests are performed selectively. These tests determine whether the nephrotic syndrome is primary (idiopathic) or secondary to a systemic disorder; and to detect the presence of associated problems or complications.
The kidney biopsy is the most important test used to determine the exact underlying type or cause of nephrotic syndrome. In a kidney biopsy, a small sample of kidney tissue is taken and examined in a laboratory.
In nephrotic syndrome the goals of treatment are to relieve symptoms, correct urinary loss of protein, prevent and treat complications and protect the kidney. Treatment of this disease usually lasts for a long period (years).
The dietary advice/restriction for a patient with swelling differs once the swelling disappears with effective treatment.
In a patient with swelling:Restriction of dietary salt and avoidance of table salt as well as foods that are high in sodium content, so as to prevent fluid accumulation and edema. Restriction of fluid is usually not required. Patients receiving high doses of daily steroids should restrict salt intake even in the absence of swelling to decrease the risk of developing hypertension.
For patients with swelling, adequate amounts of proteins should be provided to replace the urine protein loss and prevent malnutrition
An adequate amount of calories and vitamins should also be provided to these patients.
In symptom- free patients:
The dietary advice during the symptom- free period is a normal healthy diet. Unnecessary dietary restrictions should be avoided. Avoid restriction of salt and fluid. Provide an adequate amount of proteins. Avoid moderately high protein diets to prevent kidney damage and restrict protein intake in the presence of kidney failure. Increase intake of fruits and vegetables. Reduce the intake of fat in diet to control blood cholesterol levels.
Treatment of underlying causes
Meticulous treatment of underlying causes of secondary nephrotic syndrome such as diabetic kidney disease, lupus kidney disease, amyloidosis etc. is important. Proper treatment of these disorders is necessary to control nephrotic syndrome.
Monitoring and follow up
Prednisolone is the most commonly used drug for the treatment of nephrotic syndrome. Because of the possibility of several side effects this drug should be taken strictly under medical supervision.
Common short-term side effects are increase in appetite, weight gain, swelling of the face, stomach irritation causing abdominal pain, increased susceptibility to infection, increased risk of diabetes and high blood pressure, irritability, acne and excessive growth of facial hair.
Common long-term side effects are weight gain, stunted growth in children, thin skin, stretch marks on thighs, arms, and abdominal area, slow wound healing, development of cataracts, hyperlipidemia, bone problems (osteoporosis, avascular necrosis of the hip) and muscle weakness.
Serious side effects of corticosteroids are known but at the same time untreated nephrotic syndrome has its potential dangers.
Nephrotic syndrome can cause severe swelling and low protein in the body. Untreated disease may cause numerous complications, such as increased risk of infections, hypovolemia, thromboembolism (blood clots may obstruct blood vessels and cause strokes, heart attacks, and lung disease), lipid abnormalities, malnutrition and anemia. Children with untreated nephrotic syndrome quite often die from infections.
With the use of corticosteroids in childhood nephrotic syndrome the mortality rate has been reduced to around 3%. The optimal dose and duration of corticosteroid therapy under proper medical supervision are most beneficial and least harmful. Majority of steroid effects disappear with time after the discontinuation of therapy.
In order to obtain potential benefits of the therapy and avoid life- threatening complications of the disease, the developement of some side effects of corticosteroid is unavoidable.
Two independent effects of steroids are increased appetite leading to weight gain and redistribution of fat. These lead to a round or swollen face. Steroid induced moon-shaped face is seen during the third or fourth week of steroid therapy, which mimics swelling of the face due to nephrotic syndrome.
Swelling of nephrotic syndrome starts with puffiness or swelling around the eyes and the face. Later swelling develops in feet, hands and all over the body. Swelling of the face due to nephrotic syndrome is most noticeable in the morning, immediately after waking and is less noticeable in the evening.
Swelling due to steroids predominantly affects the face and abdomen (because of redistribution of fat), but arms and legs remain normal or thin. Steroid-induced swelling remains the same all throughout the day. Different characteristics of distribution and time of its maximum appearance help in the differentiation of these two similar conditions. In certain patients, blood tests are needed to resolve the diagnostic dilemma. In patients with swelling, low serum protein/ albumin and high cholesterol indicate relapse whilenormal values of both tests suggest steroid effect.
To determine precise treatment strategy in a patient, it is important to differentiate between swelling due to nephrotic syndrome and steroid side effects.
Swelling due to nephrotic syndrome needs an increase in steroid dose, modification in the method of its administration, and at times, addition of other specific drugs and temporary supplementation of water pills (diuretics).
Facial swelling due to steroids, on the other hand, is the proof of long term steroid intake, and one should neither worry that the disease is out of control nor reduce the dose of the steroid rapidly out of fear of the drug toxicity. For long term control of nephrotic syndrome, continuation of steroid therapy as per recommendation of the doctor is essential. Diuretics should not be used to treat steroid induced swollen face because it is ineffective and can be harmful.
Chances of recurrence or relapse of nephrotic syndrome is as high as 50-75% in a nephrotic child. The frequency of relapse varies from patient to patient.
When steroid is ineffective in the treatment of nephrotic syndrome, other specific drugs used are levamisole, cyclophosphamide, cyclosporine, tacrolimus and mycophenolate mofetil (MMF).
There is no need to do a kidney biopsy before starting steroid treatmen in children with nephrotic syndrome. But kidney biopsy is indicated in the presence of:
The prognosis depends on the cause of nephrotic syndrome. The mos common cause of nephrotic syndrome in children is minimal change disease which carries good prognosis. Majority of children with minima change disease respond very well to steroids and there is no risk of developing chronic kidney failure.
A small proportion of children with nephrotic syndrome may not respond to steroid therapy and may require further evaluation (additional blood tests and kidney biopsy). These children with steroid resistant nephrotic syndrome need treatment with alternative drugs (levamisole, cyclophosphamide, cyclosporin, tacrolimus etc) and have a high risk of developing chronic kidney failure.
With proper treatment of nephrotic syndrome protein leak stops and the child becomes almost normal. In majority of children, relapse occurs for many years (throughout childhood). As the child grows, frequency of relapse decreases. Complete cure of nephrotic syndrome usually occurs between the age of 11 to 14 years. These children have an excellent prognosis and lead a normal life as adults.
The family of a child with nephrotic syndrome should immediately consult a doctor if he or she develops:
Source: Kidney Education Foundation