How to Deal with Nephrotic Syndrome in Children

Nephrotic syndrome or nephrosis is a rare condition affecting both children and adults. Childhood nephrotic syndrome is usually diagnosed in children between the age of two to five and can be life-changing for the child and the parent. A clear understanding of its causes, symptoms, treatment, and prognosis can greatly help in the management of the disease.

What is Nephrotic Syndrome?

Kidneys are one of the primary excretory organs of the body and they function by separating out unwanted catabolic wastes and toxins from the body through urine. Tiny structures called glomeruli act as filtering machinery inside the kidney. When these glomeruli fail to function effectively, the filtering mechanism fails.

Nephrotic Syndrome refers to a condition in which the kidneys (glomeruli) fail to filter out the proteins from the blood and excrete it in the urine. The term ‘nephrotic syndrome’ is used to indicate the condition in which the proteins in the urine are above a certain permissible range. The exact medical condition leading to this phenomenon can be many and a deeper examination is usually required to ascertain the cause.

Types of Nephrotic Syndrome

Nephrotic syndrome in children is classified as primary childhood nephrotic syndrome, secondary childhood nephrotic syndrome, and congenital nephrotic syndrome.

• Primary nephrotic syndrome: This type of nephrosis is also called idiopathic nephrotic syndrome and many times the reason behind its occurrence is unknown. Minimal Change Disease, focal segmental glomerulosis, and membranoproliferative glomerulonephritis (MPGN) come under this type of nephrotic syndrome.
• Secondary nephrotic syndrome: This subtype of nephrosis, is caused by some kind of infection, the overdose of certain medications or an underpinning disease in the body. Diseases like diabetes, hepatitis, lupus, HIV, malaria, streptococcal infection and Henoch-Schönlein purpura are some diseases that are associated with the secondary nephrotic syndrome.
• Congenital (Finnish-type) nephrotic syndrome: This is the hereditary form of nephrotic syndrome that is transmitted from one generation to the other through their DNA. Primarily, a genetic variation in the gene NPHS1, coding for a key transmembrane protein called nephrin, causes this syndrome. It is quite rare and manifests as early as three months of age.

Causes

The causes of childhood nephrotic syndrome are many, as the syndrome is just a manifestation of an underlying condition. The various causes each type are as follows:

Primary Nephrotic Syndrome

The causes of Primary Nephrotic Syndrome are:

• Minimal change nephrotic syndrome (MCNS): MCNS is characterized by minute damages to the glomeruli in the kidney. These damages are so tiny that they are not visible only in an electron microscope. This sub-type of nephrotic syndrome contributes to nearly 15% of primary nephrotic syndrome cases. The cause for MCNS is unknown.
• Membranoproliferative glomerulonephritis(MPGN): In this condition, there is a build-up of antibodies over the minute structures of glomeruli, causing it to become thick. The causes of MPGN can be an autoimmune disease, carcinoma or some kind of infection.
• Focal segmental glomerulosclerosis (FSGS): FSGS, as the name suggests is sclerosis or scarring of a focused individual part of the glomeruli. This can cause irreversible damage to the kidneys.
• Idiopathic crescentic glomerulonephritis: This condition occurs when the glomerulus is visible as crescent shapes under a microscope. The cause for this type of idiopathic glomerulonephritis is unknown.

Secondary Nephrotic Syndrome

• Systemic diseases like diabetes (diabetic nephropathy), renal vein thrombosis, lupus erythematosus, vasculitis, Poststreptococcal glomerulonephritis, and lymphoma.
• Infections like congenital toxoplasmosis, syphilis, rubella and cytomegalovirus, HIV AIDS, Hepatitis B, hepatitis C, and malaria.
• Over-use of some drugs also can cause secondary nephrotic syndromes like usage of Penicillamine, NSAIDs (Non-steroidal anti-inflammatory drugs), Interferon, heroin, mercury, lithium and Pamidronate.

Congenital nephrotic syndrome: This type of nephritis is found associated with rare diseases caused by genetic mutations. These mutations are hereditary. i.e. passed on from one generation to the other. If a child has a family history of this disease, then there are high chances of acquiring the faulty gene from the parents. Some of the rare diseases associated with nephrotic syndrome are:

• Finnish-type congenital nephrotic syndrome
• Galloway-Mowat syndrome
• Oculocerebrorenal (Lowe) syndrome
• Nail-patella syndrome
• Pierson syndrome
• Denys-Drash syndrome
• Frasier syndrome

Symptoms

Childhood nephrotic syndrome is characterized by one or many of the following symptoms:

• Oedema: Oedema is the accumulation of water and subsequent swelling in selected parts of the body. In the case of nephrotic syndrome, oedema is found in legs, feet, ankles and around the eyes. Some patients rarely also have oedema in their face and hands.
• Albuminuria: Due to the improper functioning of the kidneys, the albumin that needs to be retained in the blood, gets excreted in the urine. This phenomenon is clinically measured and termed as Albuminuria. An increased level of albumin in the urine indicates a problem in the kidneys.
• Hypoalbuminemia: A low level of albumin in the blood, known as hypoalbuminemia is also a measure of the faulted excretory system. A blood test revealing hypoalbuminemia is a symptom of nephrotic syndrome.
• Slow growth: As proteins are essential building blocks for growth and development, a loss of proteins in the urine, affects the growth in children. Some hormonal and lipid balances are also hampered in the body.
• Infections: Loss of important proteins in the body, weakens the immune system, making them more prone to infections.

Diagnosis of Childhood Nephrotic Syndrome

For children who present with the classical symptoms of childhood nephrotic syndrome, the doctor usually prescribes the following diagnostic tests:

• Urine dipstick test: It is a simple procedure that is performed with the first urine of the day. A dipstick is used to check the urine for the presence of proteins. If the protein concentration is high, it changes the colour of the dye in the dipstick. The concentration of the protein is quantified with the help of a colour coded chart.
• Urine test: To gain further clarity on the concentration of excreted protein in the urine the doctor usually prescribes a routine urine test that accurately measures the level of albumin in the urine. A ratio of the albumin and creatinine in the urine is estimated and a high ratio of the two proteins indicates a failure of the kidneys to retain albumin.
• Blood test: As a converse, the protein levels in the blood are checked to estimate the extent to which the proteins are lost from the blood. A blood test is also used to decipher the underlying cause of the leakage of essential proteins.
• Physical exam: The doctor also checks for any visible signs of nephrotic syndrome in the child, like patchy skin, swelling of the extremities, fever, distension of the abdomen, etc.
• Family history: Due to genetic disposition, a thorough understanding of any family history of nephrotic syndrome is essential for the doctor to arrive at a correct diagnosis. Genetic testing is also prescribed in the recent times to find out the exact cause of the syndrome.
• Ultrasound of the kidney: If the urine or blood tests are suggestive of a nephrotic syndrome, the doctor carries out an ultrasound examination of the kidneys to visualize the extent of the damage in the glomeruli.
• Biopsy: In some rare cases, doctors recommend a biopsy test of the kidney tissue to rule out any malignancy and also to understand the morphology of the kidney cells. It is usually not performed on very young children, unless and until it is completely necessary.

What Category of Kids Are At the Risk of Developing Nephrotic Syndrome?

Children with idiopathic primary nephrotic syndrome do not have a clear-cut reason behind their condition and research is still ongoing in deciphering the exact risk factors for it. However, secondary nephrotic syndrome usually affects children with diseases that cause harm to the kidneys or infections that elicit an immune response. Some medications also lead to nephritis.

Children who carry mutations in the genes encoding some important proteins that are involved in the proper functioning of the kidneys can suffer from congenital nephrotic syndrome. Those children who have a known history of nephrotic disease are at a greater risk of the disease compared to other kids. Additionally, boys have a higher chance of developing nephrotic syndrome than girls, according to the available data.

Risks and Complications

Children suffering from nephrotic syndrome, primarily lose essential proteins in the urine, due to the lack of an efficient excretory mechanism. When these essential proteins are lost, it impacts the growth and development of the child. The proteins that prevent the clotting of blood are lost in children with the syndrome, making them more prone to blood clots. Children with nephrotic syndrome also are highly prone to various infections and doctors prescribe medications to counter the infection immediately after a diagnosis of nephritis. Higher blood cholesterol also occurs as a consequence of low albumin in the blood. In order to make up for the loss, the cholesterol secreted along with the albumin from the liver increases its concentration in the blood.

Further complications like are likely to be associated with this syndrome are:

• anaemia
• fluid retention
• heart disease
• blood pressure
• kidney failure

Treatment

The treatment options for nephrotic syndrome differ for each subtype of the syndrome. Some of the standard treatment options for each type of nephrotic syndrome are listed below:

• Primary nephrotic syndrome:

Primary nephrotic syndrome that is usually idiopathic is treated with different types of medications. The medications are given either to control the blood pressure or correct oedema or to lower the immune response.

1. Steroids to Reduce Immune System Activity: Many cases of idiopathic nephrotic syndrome are caused by the immune system of the body producing antibodies against their own kidney cells. In order to reduce the activity of the immune system, corticosteroids like prednisone are prescribed. These steroids not only act as immunosuppressant, but also prevent the loss of valuable proteins in the urine. This is usually the first line therapy that is prescribed for about four weeks. The dosage is then reduced and given for consumption on alternate days, for four weeks. A period of remission, where the affected children do not show any visible symptoms of nephritis, is achieved through this medication. However, in some children, there is a relapse of symptom after some time. In such cases, the doctor usually prescribes other classes of immunosuppressant along with the corticosteroids.
   Although considered one of the effective first-line treatments for childhood nephrotic syndrome, prednisone has a couple of side effects like weight gain, increased appetite, mood swings, hyper active behaviour, etc. These side effects usually fade out after the dosage is stopped. Consumption of other immunosuppressant can also expose the child to the risk of catching infections like chicken pox soon.
2. Lowering Blood Pressure: Medications that lower the blood pressure like ACE inhibitors or beta blockers are prescribed for children. The elevation of blood pressure is observed and such medications are essential to keep it under control to avoid further complications.
3. Diuretics: Edema is a very common symptom of childhood nephrotic syndrome and it is treated with diuretics. Diuretics work by excreting the excess fluid in the body.
4. Albumin Infusion: In order to restore the albumin lost from the body, doctors usually advice intravenous infusion of albumin into the blood. This method is generally used if the loss of albumin is severe.
5. Kidney Transplant: If the nephrotic syndrome is severe, the child may require a kidney transplant. Until a suitable match is found, dialysis is performed to sustain the excretion process.

• Secondary nephrotic syndrome

Secondary nephrotic syndrome is caused by certain infections, systemic diseases or over-dose of certain medications. Apart from the drugs used to treat primary nephrotic syndrome, doctors also prescribe antibiotics to treat infections causing the nephritis. Additionally, if any systemic diseases are suspected, then medications to treat those diseases are given to the children.

• Congenital nephrotic syndrome

Congenital nephrotic syndrome is caused due to certain mutations in key transmembrane proteins. Children with congenital problems usually are treated with medications that reduce the symptoms of nephritis. The only available cure is a kidney transplantation, wherein a healthy kidney from a suitable donor is used to replace the diseased one. Dialysis is performed to sustain the excretory function until a matching donor is found.

Home Remedies

Although there are no home remedies that cure the nephrotic syndrome completely, a restricted diet plan for children with nephrotic syndrome can greatly help in reducing the stress on the kidneys. The diet for such children should be planned, keeping the following points in mind.

• Low salt food, in order to keep a check on edema
• Low cholesterol diet
• Limited consumption of water, juice etc.
• Low saturated fat

A healthy balanced diet can be given to the child to boost the immunity. Proper management at home involves continuous monitoring of the albumin levels in the urine with a dipstick and diligently following the medications given by the doctor. This is sure to speed up the recovery process.

Tips to Prevent Nephrotic Syndrome in Kids

If the nephrotic syndrome is congenital or idiopathic, prevention is not possible. However, secondary nephrotic syndrome can be prevented by following these steps.

• Keeping infections away: Maintaining good health and hygiene can be very important in protecting the children from unwanted infections. Fewer infections would result in less activation of the immune system. Damage to the immune system is one of the primary reasons for nephrotic syndrome.
• Diet: A general low carbohydrate, low-fat and low-cholesterol diet can be very helpful in avoiding health complications arising out of nephrotic syndrome in children
• Exercise: Exercise is a crucial part of well-being. Children who are prone to a higher risk of nephrotic syndrome should participate in activities like walking, jogging, swimming, etc. Mild exercises that do not exert the body can be very helpful in preventing the relapse of the syndrome, during the remission period.

Congenital Nephrotic Syndrome

The congenital form of nephrotic syndrome is a rare subtype and is caused by mutations in the genes encoding some vital proteins. In some cases, it also so occurs that children acquire infectious diseases at the time of birth. Children with congenital nephrotic syndrome start showing symptoms of the disease as early as three months of age. Some of the genes, whose mutations are found to cause nephrotic syndrome are:

• NPHS1-Nephrin gene
• PLCE1- Phospholipase C-Epsilon 1
• WT1- Wilms tumour suppressor gene
• NPHS2-Pododsin gene
• ACTN4- Alpha actin 4 gene
• TRPC6- Transient receptor potential cation channel C, 6

Apart from these some rare congenital syndromes also have nephrotic syndrome as one of their symptoms, like:

• Nail-Patella syndrome
• Pierson syndrome
• Schimke immuno-osseous dysplasia
• Galloway-Mowat syndrome
• Oculocerebrorenal (Lowe) syndrome

The usual first line of treatment for congenital nephrotic syndrome is to administer albumin infusions to the child, to maintain the required level of the protein in the blood. This can be done both at the medical centre and at home, depending upon the condition of the child and the facilities available. A permanent cure to this condition is to go for a kidney transplant. In some cases, the doctor may decide to remove only one kidney or both of them, depending upon the extent of the damage. Until a suitable donor is found for the child, he or she is given dialysis treatment to mimic the function of the kidneys.

FAQs

1. Does Nephrotic Syndrome Relapse?

Yes, in some children nephrotic syndrome relapses. During the period of remission, i.e. the time at which the child is asymptomatic, there are chances for the child to start showing symptoms of relapse. It is very crucial for parents and caregivers to observe these signs and bring them to the notice of the doctor. Regular monitoring of the urine for proteins, using a dipstick is a good way to identify them. During an episode, the doctor usually prescribes a mild dose of steroid or other types of immunosuppressant, to bring the nephritis under control.

2. Does It Ever Go Away?

Usually, childhood nephrotic syndrome has a good prognosis after an episode of medications. By the time the children reach teenage, the disease is completely cured without any damage to the kidneys. Any relapses during this period can also be corrected with medications. In the case of a congenital nephrotic syndrome, a transplant is necessary to completely relieve the child of the disease.

Childhood nephrotic syndrome can be managed effectively with medications and lifestyle changes if diagnosed at an early stage. It can be a challenging phase for the child to cope with the disease and the side effects of the medications. Parents and caregivers can greatly help in the recovery process by lending a helping hand in following the medications accurately and preparing a safe and healthy diet.