Childhood nephrotic syndrome
What is nephrotic syndrome?
The nephrotic syndrome itself is not a disease. It’s considered as a clinical presentation of an underlying illness. The primary pathology of nephrotic syndrome is at the kidney level. It’s characterized by excretion of high amounts of protein in the urine, usually more than 3.5 g/dl per day. In children, it can also be defined as early morning 1st urine sample having a protein/creatinine ratio of more than 300mg/mmol or having an Albumin/creatinine ratio of more than 200mg/mmol.
The diagnosis of nephrotic syndrome is mainly clinical. The following factors are considered as the diagnostic criteria of nephrotic syndrome.
- Protein in urine more than 3-3.5 g/dl in a 24-hour spot urine collection
- Urine protein/creatinine ratio of 300mg/mmol or higher
- Serum albumin less than 25g/l
- Oedema of the body, mainly involving the ankle or sacral region
- Very high blood lipid levels
Nephritic syndrome is also another condition that involves the kidney which has a similar presentation. High blood pressure and macroscopically visible blood in the urine are suggestive of nephrotic syndrome. Usually, oedema is mild in nephritic syndrome, frequently appear as eye puffiness.
Types of nephrotic syndrome
Depending on the histological findings of the kidney, nephrotic syndrome in childhood is classified into several categories. Out of them,
- Minimal change disease (MCD)
- Focal segmental glomerular sclerosis (FSGS)
- Membranous glomerulopathy (MGP) are the commonest.
Symptoms of childhood nephrotic syndrome
- Frothy or foamy urine
- Cloudy appearance of urine when exposed to heat
- Swelling around the ankle, sacrum or eyes.
- Recent respiratory tract infection
- Difficulty in breathing
- Loss of appetite and fatigue
Causes of nephrotic syndrome/ Etiology
Most of the time, irrespective of the type of nephrotic syndrome, etiology remains unclear. Genetic factors, especially certain types of HLA alleles, may play a role in the pathogenesis of MCD. Abnormal T lymphocyte immune response is a common finding among those children. Childhood nephrotic syndrome occasionally may follow up respiratory tract infections.
Several diseases, including HIV, Hepatitis B & C, and Malaria and some drugs, especially NSAIDs, penicillamine and gold are known to cause nephrotic syndrome. Systemic vascular diseases such as systemic lupus erythematosus and leukemia are notorious to cause nephrotic syndrome as well.
Complications of nephrotic syndrome
Excessive loss of protein may progress to protein malnutrition. Albumin, an important plasma protein in the blood, falls as a result of excessive loss in urine. As a consequence, fluids in blood start to leak into the surrounding tissues. This manifests as severe oedema. Ultimately this reduces the blood volume and impairs the blood supply to the vital organs. At this stage, the child will develop multi-organ failure with hypovolemic shock and acute renal failure. Even death may result. Antibodies in blood also leak with urine. This manifests as a reduction of immunity. Therefore, children with nephrotic syndrome are vulnerable to severe infections. Accumulated fluids inside the abdomen may get infected leading to bacterial peritonitis. Any infection during an episode of nephrotic syndrome should be diagnosed early and promptly treated. Nephrotic syndrome patients have a tendency to develop blood clots inside their blood vessels. A sudden onset respiratory difficulty may be the only clue in such cases. Rarely a heart attack or even a stroke may occur.
Treatment for childhood nephrotic syndrome is mainly steroids. Minimal change disease universally responds to steroids. Initially, steroids are started as high doses of 60mg/m2/day for 4-6 weeks. Then doses are gradually tapered off. The total duration of therapy should not be less than 12 weeks. Unfortunately, other types of nephrotic syndrome occasionally respond to steroids. Even if they do, they may develop resistance over time. On such occasions, steroid-sparing drugs such as levamisole, cyclosporine, mycophenolate mofetil are used.
Long term steroid therapy
It also has many side effects including growth retardation, bone diseases, obesity, immune deficiency, etc. To tackle it, steroids can be replaced by steroid-sparing drugs, if the duration of treatment is expected to be very long.
Nephrotic Syndrome Survival -Prognosis
Minimal change disease is responsible for more than 90% of the Paediatric nephrotic syndrome cases. MCD is, by far the best nephrotic syndrome that a child can have. Light microscopic examination of the kidney tissues reveals no abnormal changes. Sequelae of MCD are absolutely perfect. These children are expected to live normal lives without any renal impairment. Nephrotic syndrome settles as they get older. Almost all the children will be free of the nephrotic syndrome once they have reached their twenties.
Conversely, FSGS and MGP have a poor outcome. Those children suffering from FSGS or MGP will ultimately present with chronic renal failure despite having adequate treatments.
Some further good reads