What is Nephrotic Syndrome in Children?

Nephrotic Syndrome in children is the occurrence of the following symptoms together: low albumin in the blood, proteins occurring in urine, swelling of the body and excessive lipids (fats) in the blood. It is a Kidney disease that affects both kidneys and if not treated, may lead to serious side effects such as kidney failure and even death. When these symptoms occur together, the condition is termed as Nephrotic syndrome.

When you notice the body of your child suddenly swells especially in the morning (mostly eyes swelling), it means the child most likely has Nephrotic syndrome because nephrotic syndrome frequently results in edema (body swelling). Nephrotic syndrome does not usually cause blood in urine (hematuria, which is reddish urine as a result of blood) but may occur even though in rare conditions. Other symptoms and signs of Nephrotic syndrome may not be seen unless laboratory tests are done to confirm it due to the fact that there are many other diseases such as Acute Glomerulonephritis (AGN) or Chronic Hepatitis B or Hepatitis C viral infections that can make the body of children to swell.

It is the most common type of Kidney disease in Children. Kidneys are responsible for making of urine and also help the body to regulate the amount of red blood cells produced by the body. The kidney also helps to control the amount of water in the body and also helps in the production of Vitamin D needed for calcium absorption in the body. With these functions, if the kidney is affected, then its functions would cease which would cause the associated complications seen in the disease. In order to understand what Nephrotic syndrome is especially for non-medical users, explanation of medical terms would be made and use of technical or medical terms would be reduced unless otherwise necessary.

Epidemiology of Nephrotic syndrome

Idiopathic nephrotic syndrome has a reported incidence of 2 to 7 cases per 100,000 children in North America and a prevalence of nearly 16 cases per 100,000. Mostly presents in the age range of 1-10 years. Males are more likely to be diagnosed with nephrotic syndrome than females.

Signs and Symptomsof Nephrotic syndrome

A symptom is what a doctor sees and a sign is what a patient complains of. The symptoms of Nephrotic syndrome therefore are:

1. Low protein in the blood: this is referred to as hypoalbuminaemia. Albumin is an important protein in the body needed for control of fluid across the blood vessels and also for transportation of certain substances (hormones, fatty acids, steroids, drugs, etc) in the blood to other parts of the body. Hypoalbuminaemia therefore refers to low albumin in the blood. Because of low albumin, it means that water cannot be controlled across the blood vessels again and other functions of albumin will be limited too.
2. Proteins in urine: since the proteins in the blood have been excreted in urine because of the inability of the kidney to sieve the proteins, there will be presence of proteins in urine in large amounts. This is the cause of the low protein in the blood as stated above.
3. Excessive amounts of fatty acids and other lipids occur in the blood: since albumin binds and transport fatty acids and other lipids in the blood, it means therefore that when there is little amount of albumin, then fatty acids would accumulate leading to excess lipids in the blood because the transport to other parts of the body is impaired due to inadequate albumin.
4. Body swelling: since albumin controls the movement of water across the blood vessels by regulating the pressure in the blood (plasma oncotic pressure) and that of the spaces outside of the blood spaces (Interstitial space). It means that when albumin is low, then the fluid in the blood can freely move across to spaces outside of the blood vessels leading to accumulation of fluid in the body causing body swelling.

The above symptoms occur together in Nephrotic syndrome.

 

Signs of Nephrotic syndrome

Since signs are what the patient sees or complains about, the following signs may occur in Nephrotic syndrome especially in rare cases:

1. Blood in urine
2. Headache
3. Hypertension
4. Inability to breath well due to collection of fluid in the lung sac (pleural effusion)

Nephrotic syndrome could occur in both children and adults. In fact, there is type of Nephrotic syndrome known as Congenital Nephrotic syndrome that occurs in newborn babies. This type occurs more in Finland hence the name: congenital Nephrotic syndrome of the Finnish type.

Etiology of Nephrotic syndrome

Nephrotic syndrome is caused by various factors of which some are known and some are not yet known by doctors. The causes of that are not known are termed medically as Idiopathic. Idiopathic (unknown cause) Nephrotic syndrome is also called Primary Nephrotic syndrome because it is occurring in the Kidney. If Nephrotic syndrome occurred due to a disease process in other parts of the body, then it is called Secondary Nephrotic syndrome. The causes of the Secondary Nephrotic syndrome are known.

Causes of Nephrotic syndrome in children

1. Malaria infection: if you live together with your child in Africa, especially in West and east Africa, then this may be the cause.
2. HIV/AIDS
3. Cytomegalovirus
4. Syphilis and Congenital syphilis
5. Hepatitis B and C infections
6. Rubella (measles)
7. Toxoplasmosis
8. Leprosy
9. Schistosomiasis: This occurs mostly in Egypt
10. Filaria worms causing diseases such as Onchocerciasis and Loiasis
11. Penicillamine because it is a Nephrotoxic agent (drug that destroys the kidneys)
12. Gold poisoning: also nephrotoxic
13. Mercury poisoning (also nephrotoxic) through the use of mercury containing soaps or creams such as Peau Claire, Bio Claire, Mekako, Elegance,Rico etc
14. Metabolic causes such as in uncontrolled Diabetes mellitus and amyloidosis
15. Cardiovascular diseases such as Renal vein thrombosis
16. Sickle cell disease, Alports syndrome and lymphomas
17. Collagen diseases such as Systemic Lupus Erythamatosus, Henoch-Schonlein Purpura,
18. Allergies following Bee stings

In order to understand the causes of Nephrotic syndrome, it is best classified first.

Types/Classification of Nephrotic syndrome

1. Primary Nephrotic syndrome
2. Secondary Nephrotic syndrome: not directly caused by kidney disease but a systemic problem that later affects the kidney leading to Nephrotic syndrome.
3. Congenital Nephrotic syndrome: the child was born with it. They are often born with large placentas and causes fetal distress at birth. Most babies having this type are born premature.

Primary Nephrotic syndrome

The cause of this type is unknown (Idiopathic) but occurs as a result of direct impairment of normal function occurring in the kidney. There are different types of Idiopathic Nephrotic syndrome which include:

1. Minimal change disease
2. Membranoproliferative glomerulonephritis
3. Focal glomerulosclerosis
4. Mesangio-proliferative glomerulonephritis
5. Membranous nephropathy

These forms are classified according to how they appeared when viewed with a microscope (Light or electron microscope) i.e. according to their histological types. If you are not a doctor, dont bother yourself with this, after all, this article was intended for education and not to help you manage a child with Nephrotic syndrome.

Secondary Nephrotic syndrome

This occurs as a result of disease occurring somewhere different from the kidney but later on affecting the kidney and causing secondary Nephrotic syndrome.

Pathophysiology of Nephrotic syndrome

The kidney filters unwanted products and excretes them out of the body. This is done by the part of the kidney called glomerular membrane. Nephrotic syndrome develops as a result of changes in this membrane whereby there is increase in the permeability of the glomerular membrane. This increased permeability leads to increase filtration of proteins out of the body. The main protein affected is Albumin. Albumin is needed by the body to keep fluid in the blood vessels; a reduction of Albumin in the blood therefore means that the fluids will move out of the blood vessels into the body tissues leading to swelling of the body that is known as Edema. When all the parts of the body are affected, it is referred to as Anasarca (Generalized body swelling).

Laboratory investigations (Tests) to confirm diagnosis of Nephrotic syndrome in Children

Laboratory findings in Nephrotic syndrome include:

1. A urine dipstick shows proteinuria that is 3+ to 4+
2. Total serum protein is reduced and albumin level is low
3. In uncomplicated cases, the electrolyte, urea and creatinine levels are normal
4. There may be elevation of serum cholesterol, triglyceride and phospholipids
5. Complement C3 level and Anti-Streptolysin O (ASO) titre is normal (these are used to differentiate Nephrotic syndrome from Acute Glomerulonephritis where these components are low.
6. Renal biopsy if indicated can also be used to help in prognosis

Indications for Renal Biopsy in Nephrotic syndrome

1. Nephrotic syndrome with low serum complement C3
2. Steroid resistant Nephrotic syndrome
3. Nephrotic syndrome in children occurring in the 1^st year of life
4. Nephrotic syndrome being considered for cytotoxic therapy such as frequent relapse and steroid dependent types.

Absolute Contraindications to renal biopsy in Nephrotic syndrome

1. Solitary kidney
2. Bleeding diathesis
3. Severe asthenia
4. Uncontrolled hypertension
5. Intra renal tumor
6. Small scarred kidneys with end stage renal disease

Relative Contraindications to renal biopsy in Nephrotic syndrome

1. Perinephric abscess
2. Hydronephrosis
3. Nephrocalcinosis
4. Severe anemia
5. Marked obesity

Differential diagnosis of Nephrotic syndrome

1. Acute glomerulonephritis
2. Protein Energy Malnutrition such as Marasmus and Kwashiorkor
3. Protein loosing enteropathy
4. Chronic liver disease
5. Congestive cardiac failure
6. Kidney failure
7. Fluid overload

Management/Treatment of Nephrotic syndrome in Children

The doctor explains the nature of the disease clearly to the Parents of the child because they are often disturbed seeing the body of their children swollen especially the eyes swelling, abdominal swelling (ascites) and even testicular swelling or other parts of the body.

Nephrotic syndrome diet

Patients are then placed on a high protein diet that is low in salt and high in carbohydrates. Such a diet for Nephrotic syndrome patient should contain enough meat or fish or eggs (animal proteins more preferable than plant protein), if possible, no salt or little amount of salt and high carbohydrates such as rice, corn or wheat. This diet helps to replace the lost protein content in urine especially the Albumin that was lost and the low salt controls the body swelling.

Use of diuretics to control body swelling

Drugs such as the thiazides, spironolactone and frusemide are called diuretics because they increase the frequency of urination (that is they help the body get rid of water). They are used to control the body swelling. If the swelling is persistent even with diuretics, then salt-poor albumin is used by giving it through the veins (Intravenously) and at the end of the infusion, Frusemide is then given intravenously too.

Children with Nephrotic syndrome living in the tropics are also treated for malarial infection too.

Use of steroids in Nephrotic syndrome

Steroids are the main stay of treatment in Nephrotic syndrome especially for those having minimal change disease. Prednisolone is used and is given for 4 weeks during which the protein in urine (proteinuria) is expected to cease.

1. Steroid responsive Nephrotic syndrome: these children respond well to treatment with steroids and their symptoms regress within 4 weeks of treatment. A cure can be achieved.
2. Steroid Resistant Nephrotic syndrome: there is persistence of protein of 2+ in urine even after treatment with steroids for 8 weeks.
3. Steroid Dependent: in this type, there is nephrotic syndrome relapse shortly after stopping treatment with steroids. What is a Nephrotic syndrome relapse? It is the reoccurrence of the symptoms of nephrotic syndrome after initial reduction or cessation following treatment.
4. Frequent relapsers: this type occurs when there are four or more episodes of relapse in a year. (>4 relapse in 12 months) or 2 or more relapses within the first 6 months of presentation.

Those who do not respond to steroid therapy or who have relapse or suffer steroid toxicities are tried on immunosuppressive drugs such as cyclophosphamide or chlorambucil. Cyclosporine could also be used but if there are signs of toxicity with cyclosporine, then Mycophenylate Mofitil (MMF) is used; Levamisole may be used but requires continuous use.

Non immunosuppressive therapy include: use of Vitamin E supplements, Non-Steroidal Anti Inflammatory Drugs (NSAIDs) and ACE inhibitors.

Indications for hospitalization of Nephrotic syndrome patient

1. Severe anarsaca
2. Need for parenteral diuretics
3. Severe infections associated with Nephrotic syndrome
4. If there is need for renal biopsy

If a child has any of the above, he or she would be admitted.

Complications/Side Effects of Nephrotic syndrome

1. Infections especially spontaneous bacterial peritonitis caused by streptococcus pneumoniae
2. Arterial thrombosis
3. Hypertension
4. Coagulation factors deficiency leading to prolonged bleeding
5. Growth retardation: the child fails to grow normally as normal children of the same age group
6. Malnutrition such as Protein Energy Malnutrition (Kwashiorkor)
7. Hypovolaemia as a result of poor use of diuretics

Prognosis of Nephrotic syndrome

Children with minimal change disease histological type of Nephrotic syndrome have favorable prognosis and have a higher survival rate than those having quartan malaria nephropathy in which most deteriorate in 5 to 10 years and may develop hypertension with subsequent chronic renal disease.