What is Childhood Nephrotic Syndrome?
Childhood nephrotic syndrome (NS) is acomplex condition consisting of distinct subtypes of glomerular histopathology and clinical courses in children. It is also called nephrosis and occurs when tiny structures in the kidneys called glomeruli stop working properly. Most commonly it is a condition that causes the kidneys to leak large amounts of protein into the urine.
Nephrotic syndrome is defined as massive proteinuria (>40 mg/m2/hr), hypoalbuminemia (<2.5 g/dL), edema, and hyperlipidemia in most of the cases. It occurs mostly in young children between the ages of 1 ˝ and 5 years, although children of all ages and even adults can get affected. It has been reported to show a prevalence of nearly 16 cases per 100 000.
The causes of Childhood Nephrotic Syndrome can be divided into three categories.
- Primary Childhood Nephrotic Syndrome – it mainly includes Minimal-change nephrotic syndrome (MCNS) and Focal segmental glomerulosclerosis (FSGS). collectively called Idiopathic Nephrotic Syndrome. About 80% children suffering with idiopathic nephrotic syndrome show remission of proteinuria following treatment with corticosteroids, and are therefore, classified as steroid–sensitive nephrotic syndrome.
- Minimal-change nephrotic syndrome (MCNS) - In minimal change disease, there is damage to the glomeruli involved in urine formation. The damage is only visible under an electron microscope. It can be related to allergic reactions, Use of non-steroidal anti-inflammatory drugs (NSAIDs), tumors, vaccinations (flu and pneumococcal) and viral infections. Many studies show that there is a high incidence of minimal change nephrotic syndrome in Asians.
- Focal segmental glomerulosclerosis is described as scarring (sclerosis) in the kidney. It occurs rarely and can lead to permanent kidney damage.
- Secondary Childhood Nephrotic Syndrome- The cause of secondary childhood nephrotic syndrome is an underlying disease or infection that causes changes in the kidney function. The most common secondary cause of nephrotic syndrome in children is diabetes.
- Congenital (Inherited) Nephrotic syndrome- It is a very rare form of nephrotic syndrome and develops shortly after birth affecting infants in the first 3 months of life. Mutations in the transmembrane protein known as nephrin cause congenital (Finnish-type) nephrotic syndrome.
Childhood nephrotic syndrome occurs mostly in children between the ages of 2 and 6. Some of the risk factors include the following:
- Family history of kidney disease: A family history of kidney disease is associated with an increased risk of childhood NS
- Gender: Boys are affected more often than girls
- Certain medications, such as NSAIDs (e.g. celecoxib) and some antibiotics
- Certain types of infections, such as HIV, Hepatitis B & C, and malaria.
- Environmental factors
The signs and symptoms of childhood nephrotic syndrome include:
- Edema - Edema is the prominent feature of nephrotic syndrome and initially develops with swelling around the eyes and legs, feet, or ankles and less often in the hands or face.
- Albuminuria - When a child’s urine has high levels of albumin (>40 mg/m2/hr).
- Hypoalbuminemia - In this condition, a child’s blood has low levels of albumin (<2.5 g/dL).
- Hyperlipidemia - Hyperlipidaemia, with raised serum cholesterol and triglyceride concentrations, is another major symptom of nephrotic syndrome. In this case the child’s blood cholesterol and fat levels are higher than normal. This clinical manifestation occurs from interactions between disordered lipoprotein metabolism, medications, and dietary factors.
Following parameters should be considered for diagnosing Childhood Nephrotic Syndrome:
- A medical and family history- In most cases a detailed and precise medical or family history is checked by the healthcare provider and it gives a definite clue to the diagnosis. Through this history, the doctor will gather more data about signs and symptoms, allergy or related diseases.
- A physical exam-. During a physical examination, a health care provider most often examines for abdominal distension and tenderness, patches on the skin, fever and blood pressure.
- Urine tests- The doctor performs following urine tests to help determine if a child has childhood nephrotic syndrome.
- The dipstick method (colorimetric reagent strip)- This test is based on the ability of proteins to alter the color of specific acid–base indicators, like tetrabromophenol blue, without changing the pH. It detects the presence of albumin in the urine. When the dye is buffered at pH 3, it is yellow; on increasing the concentration of protein it changes the color to green and then to blue. The developed color is compared with a color chart which allows the protein concentration to be graded from trace to 4 +, corresponding to concentrations from 1 to 10 mg/dl to greater than 500 mg/dl.
- Sulfosalicylic acid test- It requires centrifugation of the urine followed by addition of 2.5 ml of the supernatant to 7.5 ml of 3% sulfosalicylic acid. The degree of turbidity is quantified to the amount of albumin present in urine.
- Urine High Performance Liquid Chromatography- This is a new test, based on high-performance liquid chromatography analysis. It is able to detect all the immunoreactive intact albumin and non-immunoreactive intact albumin (total intact albumin) in urine which are not detected by dipstick test.
- Ultrasound of the kidney- Ultrasound is the preferred imaging modality to diagnose kidney damage due to pediatric nephrotic syndrome. The advantages of ultrasonography include high accuracy, the ability to detect lead points, and absence of radiation. Computed tomography (CT) and magnetic resonance imaging (MRI) or additional imaging may be needed in complex clinical situations like presence of lymphoma.
- Kidney biopsy- Inspite of the new and less invasive tests available today, renal biopsy is still considered suitable by most nephrologists as an important tool in diagnosis and prognosis and in deciding therapy in many renal diseases. Most nephrologists refrain from doing a renal biopsy in the pediatric patients as most of them respond to therapy with steroids but in adults almost everyone performs a biopsy before starting therapy.
- Blood test- In case of nephrotic syndrome, a blood test may show low levels of the protein albumin (hypoalbuminemia) specifically and overall decreased levels of blood protein (being below its normal range of 3.5-4.5 g/dL). Serum creatinine and blood urea also may be measured to assess your overall kidney function. The normal serum creatinine level of a child is approximately 0.5 mg/dL, values higher than this in children indicate reduced kidney function.
- Corticosteroid therapy- The main treatment for childhood nephrotic syndrome is steroid therapy. A trial of corticosteroids is the first step in treatment of idiopathic nephrotic syndrome (INS). Children once diagnosed with nephrotic syndrome are treated normally with steroids (prednisolone) for the first time for at least a four-week course, followed by a smaller dose every other day for four more weeks. Some children who are steroid responsive require high doses of prednisone to remain in remission.
The most common cause of steroid-resistant nephrotic syndrome is focal segmental glomerulosclerosis so these patients are treated with a specific protocol that involves multiple infusions of high-dose methylprednisolone and, in many cases, oral alkylating agent therapy is also used.
Some studies also show that the use of cyclosporine and angiotensin-converting enzyme inhibitors in the treatment of children with different forms of the nephrotic syndrome is useful. Children with steroid-responsive nephrotic syndrome tend to respond to treatment with oral cyclosporine as much as they do with prednisone.
- Diuretics- Severe edema in children with nephrotic syndrome may be associated with volume contraction (VC) or volume expansion (VE). According to a study, fractional excretion of sodium (FeNa) is useful in distinguishing VC versus VE in children with severe edema. Metolazone may be beneficial in combination with furosemide (Lasix) for resistant edema.
- Home monitoring- Regular weight record and urine examination should be done by parents for their children.
- Vaccinations- Children with nephrotic syndrome are advised to have the pneumococcal vaccine. Some children may also be recommended the chickenpox vaccination between relapses.
The only way to prevent nephrotic syndrome is to control the diseases that can cause kidney infection or damage. Prevention of early relapse in case of Idiopathic nephrotic syndrome can be done through partial cortisol substitution. It prevents half the relapses predictable within three months of remission.
Children who have nephrotic syndrome may need to make changes to their eating habits and set up a healthy lifestyle to boost immunity. Parents and caretakers should prepare healthy and balanced diet, and guide their children to do some exercises regularly, and get enough sleep.
- Childhood nephrotic syndrome: clinical associations and response to therapy. - (https://www.ncbi.nlm.nih.gov/pubmed/432155)
- Childhood Nephrotic Syndrome - (https://www.kidney.org/atoz/content/childns)
- Nephrotic syndrome in childhood. - (https://www.ncbi.nlm.nih.gov/pubmed/12944064)
- Treatment of Childhood nephrotic syndrome - (http://jasn.asnjournals.org/content/3/4/889.long)
- What is childhood nephrotic syndrome? - (https://www.niddk.nih.gov/health-information/health-topics/kidney-disease/nephrotic-syndrome-in-children/Pages/index.aspx)
- Epidemiology and Pathophysiology of Nephrotic Syndrome–Associated Thromboembolic Disease - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302669/)
- High incidence of minimal change nephrotic syndrome in Asians - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1777627/pdf/archdisch00716-0030.pdf)
Latest Publications and Research on Childhood Nephrotic SyndromeCerebral arterial thrombosis in a child with nephrotic syndrome. - Published by PubMed
Heterozygous COL4A3 Variants in Histologically Diagnosed Focal Segmental Glomerulosclerosis. - Published by PubMed
Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic Syndrome. - Published by PubMed
Mother's obesity and high child's waist circumference are predictive factors of severe child's obesity: an observational study in French Guiana. - Published by PubMed
Genetic diagnosis of steroid-resistant nephrotic syndrome in a longitudinal collection of Czech and Slovak patients: a high proportion of causative variants in NUP93. - Published by PubMed