What is Nephrotic Syndrome?

Nephrotic syndrome is a disease caused by impairment of one of the various functions of the kidney. This function involves conservation of proteins. Blood is cleaned by the kidneys through filtration from a large number of tiny capillaries that are arranged in clusters (each cluster called a “glomerulus”). These have a sieve- like function, letting small-sized substances leak out, but keeping the large ones in. Normally a negligible amount of protein is present in the urine, because during the process of filtration (the first step in the excretion of wastes and toxic products from the body) blood proteins are held back. The size of protein molecules is too large to pass through the wall of the minute blood channels (glomerular capillaries). In nephrotic syndrome there is some abnormality of the capillary walls that makes them leaky and allows heavy loss of protein in the urine. Examination of urine for protein gives a 3+or4+ reaction. Urine test from a normal person shows “nil” for protein. Severe protein loss in urine eventually results in a fall in the level of protein in the blood.

What causes this leak of protein?

The exact cause of the large amount of protein leak from the minute blood channels (capillaries) of the glomeruli is not known. In about 95% cases of nephrotic syndrome in children, there is no permanent damage to these capillaries. With treatment the leakage of protein stops. These cases are considered to have “minimal change nephrotic syndromme”.

In a very small proportion of children other diseases are present that cause capillary damage in the glomeruli, which results in leakage of protein. The doctor will carry out appropriate laboratory tests to diagnose these.

Symptoms of Nephrotic Syndromme

With continuing loss of protein in the urine the concentration of proteins in the blood decreases. Once the level of blood proteins falls below a critical level, swelling (or edema) will develop. The swelling first appears on the face, around the eyes. It is most prominent in the morning when the child gets up. Towards the evening, as he is up and about, the swelling disappears. Infact the accumulated fluid has shifted down to the legs where it is not so easily noticeable. The child is otherwise well and active and does not look ill. The swelling gradually increase to involve the feet, legs, hands and abdomen. If untreated, the swelling may become enormous with distension of abdomen due to collection of fluid. At this stage the quantity of urine may decrease. Abnormal excretion of protein in urine (“proteinuria”) starts several days before the swelling on the face is noticeable.

What is the cause of Nephrotic Syndrome?

In most cases in children the exact cause of nephrotic syndrome is not known. The disease occurs in children all over the world. It is not caused by bacterial or viral infection. There is no relationship with diet or socio-economic status of the family. It is not infectious and does not transfer to other family members. Only in exceptional instances, more than one child in a family may suffer from nephrotic syndrome.

Laboratory Tests

  1. Examination of urine for protein
    Examination of urine for protein is the most useful and simple test for the diagnosis of nephrotic syndrome and forms an important part of the long-term care. The test is very simple to perform. Urine, preferably the first specimen passed in the morning, is collected in a clean container. The specimen should have a yellow tinge; urine passed after the child has received lasix looks like water and is not suitable for testing.
  2. Treatment of Nephrotic Syndrome
    After careful clinical assessment and examination of the laboratory reports the doctor will have a good idea of the problem and the line of management. In most cases he will prescribe prednisolone. Occasionally, if the child had passed frank blood in the urine or has increase in his blood pressure, prednisolone may not be started and the doctor may advise that a kidney biopsy should be done.
    Before starting this medication the doctor will treat any infection (sore throat, chest infection, etc.) that might be associated. If the child has very marked swelling on the body, appropriate medications to reduce it will also be given.

Prednisolone Treatment

Prednisolone tablets come under different names such as wysolone, deltacortril and hostacortin, etc. They also have different weights. Thus one tablet may contain 5mg, 10mg or 20mg of prednisolone. The amount of prednisolone to be given depends upon the weight of the child. The starting dose is about 2mg / kg body weight. The doctor will explain exactly how many tablets are to be given in one day and at what intervals.

  1. Daily treatment
    For the first 2 to 4 weeks, the required number of tablets are given every day in 3 to 4 divided doses (referred to as daily treatment). The tablets are taken with a glass of milk. Other sweetening agents such as honey or ice cream may be used to mask the bitter taste of the tablets. Prednisolone may sometimes cause stomach upset (pain and burning, vomiting) and therefor it is usual to give an antacid preparation (digene, gelusil, diovol) at the same time.
  2. Alternate-day treatment
    After 2 to 4 weeks of daily treatment most children become completely well. The swelling(edema) disappears, and urine no longer contains protein (“Nil” test). At this stage, prednisolone schedule is changed over to the alternate-day treatment. The total number of tablets previously being given in one day, are now given, all at one time, as a single dose at about 8 a.m., on every alternate day. Thus the interval between two consecutive doses would be 48 hours. The tablets are given with a glass of milk; some times digene or gelusil may be added. The alternate day treatment is usually given for 8-12 weeks in decreasing doses and then stopped.

Drugs for swelling (edema)
If the child has very prominent swelling, treatment will be needed to reduce the accumulation of fluid. Usually, lasix tablets are prescribed. One dose in the morning is often adequate; occasionally a second dose in the after noon may be needed. If the swelling of abdomen is prominent, aldactone may be necessary, in 3 to 4 doses/day . the number of tablets will be prescribed by the doctor. Rarely the abdominal fluid may need to be drained through a needle inserted in the abdominal cavity.

Diet
The child should be given a diet with a plenty of proteins. High protein dietary articles include milk and milk products such as curd and cheese, dal, chana, soyabean, lobia etc. and eggs, meat and fish. Extra protein is necessary only while the child is passing protein in the urine and is receiving prednisolone. Subsequently he should be given his usual diet.
The intake of salt should be reduced while the child has swelling. The usual amount used in ordinary cooking is permitted, but he should not be given extra salt and snacks. As soon as the swelling disappears, the child can have his usual, normal diet. It must be understood that salt has no role in the causation of nephrotic syndrome. No benefit can be expected by prolonged restriction of salt, unless advised by the doctor for some other reason (e.g. if the child'’ blood pressure is high).

General Care
Besides administering prednisolone and other drugs that may be needed, no particular care is necessary. Bed is not required unless the swelling is very severe, or the child has some additional problem. Once the swelling disappears, he may go to school, and resume his usual physical activity.

Long-term Supervision
In most cases the child with nephrotic syndrome becomes completely normal with prednisolone treatment. He may remain well for several months or longer. In a majority of cases, however, the condition recurs. The recurrence is indicated by appearance of swelling around the eyes, and if untreated gradually increases to involve the face, feet, legs and abdomen, usually in that order. Urine examination again shows 3+ to 4+ of protein. The situation is called a “ relapse”. A relapse can be detected before the appearance of swelling on the face, if urine test for protein is done once or twice a week on a long-term basis, since edema occurs only after several days of presence of protein in the urine . Usually, relapses occur after a cold or sore throat or some other infection, but sometimes there is no obvious cause for relapse.

Treatment of Relapse

On some occasions proteinuria develops when the child has a cold or sore throat, but completely disappears within a week or so, along with recovery from the infection. It is , therefor, important to perform daily urine tests during an episode of infection, while the infection is being appropriately treated. Urine may show 1+ or 2+ reaction for a few days and then gradually become “nil”. No treatment is necessary for such a short spell of mild proteinuria. On the other hand, proteinuria may continue to increase(3+or 4+) even when sore throat or cold or other infection has subsided. After 1 or 2 weeks of such heavy proteinuria, swelling would appear over the face and gradually increase. Such an episode (relapse) will need treatment with prednisolone, which must be started before the swelling becomes very prominent . The drug is initially given daily in 3 or 4 divided doses, the number of tablets depending upon the weight of the child. If the swelling has increased, lasix may be given for a few days. The daily treatment is usually needed for about 2 weeks, during which urine will gradually become free of protein, showing a “nil” reaction. At this stage prednisolone is changed to the alternate-day schedule, which is continued for 8-12 weeks in decreasing doses and then stopped.

It is most important to treat a relapse early. Once the child develops gross swelling with large amount of fluid in the abdomen , the management becomes more difficult, and serious complications may occur.

Side-effects of Prednisolone Treatment

Prednisolone, when given daily, may cause pain and a burning sensation in the abdomen. Therefor, antacid liquid or tablets are given along with it. When alternate day treatment is given, it may suffice to give prednisolone tablets with a glass of milk.

On daily prednisolone treatment, the child usually has an increase in appetite. After a few days the cheeks look prominent and more pink. A more generalised obesity may develop, especially around shoulders and abdomen if the daily prednisolone treatment has to be given repeatedly. The obesity must not be confused with swelling around the eyes, over the feet and legs, which is a manifestation of the underlying disease, and is associated with 3+ or 4+ protein in urine. Dietary restriction of butter, ghee and fried articles is recommended while the child is receiving daily prednisolone treatment.

There may be an increase in hair on the face and some time on the arms and legs, which will disappear when the drug is stopped. The blood pressure may show a slight increase during daily prednisolone treatment, occasionally requiring medication to bring it down. The blood pressure is regularly monitored as long as the child is taking prednisolone. In some cases the child may show changes in mood and behavior. He may show unusual cheerfulness and increased activity or, occasionally , laziness and depression. In adolescent girls acne may be aggravated.

Large amounts of prednisolone if given for prolonged period or used repeatedly may cause slowing of the growth. The child's’ height should be regularly monitored, and if they delay in growth is of serious concern the dose of prednisolone should be reduced to bare minimum necessary and other drugs used.

The side-effects of prednisolone are much less when it is given on alternate days in small amounts, even over a period of several months.

General long-term Care and Precautions

The child usually feels well and unless the edema is very severe or there is some other complication, restriction of physical activity and games is not necessary. Infact such activities should be encouraged. He should not be kept away from school. He also should not be regarded as sick or “delicate” or made to feel different from other children. Usual disciplinary measures, as for other children in the family, should be employed.

  1. Infections
    The child with nephrotic syndrome is more likely to suffer from infections, especially when he is getting prednisolone. Usually the infections are mild, such as cold, sore throat, diarrhea and chest infections. The doctors should be consulted and appropriate treatment carried out. Occasionally, the infection is serious and may develop quite rapidly. If the child complains of pain in abdomen and vomiting and has fever he should be promptly shown to the doctor. If he has headache, vomiting, drowsiness and fever, he must be immediately taken to the hospital. The likelihood of a serious infection is more if the child is having a relapse and there is fluid in the abdomen (ascites). A delay in the treatment of such infections may have grave consequences.
  2. Immunizations
    Administration of various vaccines e.g. against mumps, measles, rubella (MMR, DPT and polio) should be postponed, if the child is in relapse (passing protein in urine) and is taking prednisolone. Vaccinations during such a state are not very effective. These will be administered after the child has stopped taking prednisolone for at least 3-6 months.

Frequency of Relapses

A child may not have a relapse for several months . Some children may develop one or more relapses in one year. Each relapse is treated with prednisolone as mentioned above. If more than 3 relapses occur within a year, some other form of treatment may be considered. The most frequent method is to keep the child on alternate-day prednisolone treatment for 1 year or more. If such a regimen does not prevent relapses, other medications may have to be given. The need for such treatment will be carefully considered by the doctor and discussed with you. Some of these other medicines include the following:

  1. Methylprednisolone or dexamethasone given by intravenous injections.
  2. Levamisole tablets given on every alternate day for a prolonged period.
  3. Cyclophosphamide. This is a drug often used in various forms of cancer. It use in nephrotic syndrome has nothing to do with cancer. This drug has been found to be beneficial in a large proportion of children with nephrotic syndrome all over the world. Usually tablets are given daily along with prednisolone for 8to12 weeks. Rarely cyclophosphamide may be given by injection once a month. The side-effects of this drug and other precautions will be explained to you by the doctor.
  4. Cyclosporine. This drug is chiefly used in patients who undergo kindly transplantation . However, it has been found to be very useful in many other conditions. It is also effective in preventing relapses in nephrotic syndrome. The doctor will discuss and explain various issues in case cyclosporine is to be administered.
  5. MMF (Mycophenolate Mofetil) is a new drug used as an adjurnt in treatment in steroid resistant, steroid responsive Nephrotic Syndrome. Use of this Medicine can reduce dose of steroid and give prolonged remission.

Renal Biopsy

A biopsy of the kidney is usually necessary if the nephrotic syndrome does not seem to be of the minimal change type, if the relapses are too frequent or proteinuria is not abolished by prednisolone treatment. The biopsy is done under local anesthesia , using a special needle. The child is given a sedative by injection about ½ hour before the biopsy. He lies prone with a rolled sheet below his abdomen to push the kidneys closer to the surface. In some instances the biopsy may be carried out with ultrasound guidance. A 4 to 6 mm long and 1mm wide piece of the superficial part of the kidney is obtained and subjected to special pathological examination. The procedure of renal biopsy is relatively simple and without any significant complications. Blood may appear in the urine, but it clears within a day or two. The child is kept in the hospital for one day. Kidney biopsy must, however, be carried out only at special centres. The doctor will explain the need for the biopsy and give other necessary information.

The result of kidney biopsy will be discussed with you. The doctor will explain the likely course of the disease and the outcome. He will prescribe the necessary medications and other measures.

When Does a Child with “ minimal change nephrotic syndrome” Finally recover?

Nephrotic syndrome is a disease that lasts over several years. It will not go away in a short time with any kind of treatment. In the minimal change variety the child remains quite normal during period of remission. In nephrotic syndrome of the other types, the child may have varying degree of problems (e.g. high blood pressure) that persist throughout. The cooperation of the patients is extremely important in the treatment of the child and , along with the doctor, they bear a heavy responsibility.

  1. Maintenance of a diary
    The parents need to maintain a careful account of the child’s treatment, urine tests and other events. The information may be recorded under 5 headings, as shown below:
    Date Urine Test Prednisolone Other drugs Remarks
    10/1/94 3+ 2 tablets each of 5mg 3 times a day Lasix
    1 tablet
    Slight cold and cough
  2. Know all about nephrotic syndromme
    The parents should clearly understand the treatment schedule, and become familiar with the few drugs used in the management. The child should not be given any unknown drugs; all prescriptions form doctors should be retained. The parents should accept a number of facts about nephrotic syndrome:
    (a) it is very likely to last over a period of several years,
    (b) the course of the disease is variable and whereas some children get only a few relapses, other have frequent relapses,
    (c) eventually, after a number of years, most children are completely cured, (d) with correct management the child will lead a normal life. If regular urine testing is done, the relapse will be detected early and treated promptly; schooling will rarely be interrupted,
    (e) no other form of treatment e.g. homoeopathy or other unorthodox therapy is likely to benefit this condition, and may prove harmful,
    (f) no better treatment is available anywhere else in the world,
    (g) the condition is not familial, and it is very rare for more than one child in a family to be affected.