Pediatric Nephrotic Syndrome – General Overview
Pediatric Nephrotic Syndrome (NS) is not so much a disease, but rather a collection of symptoms that serves as a sign of kidney damage. There can be several different potential causes of NS including bacterial, viral, and genetic defects. Studies report an incidence of 5 cases per 100,000 children worldwide, with the highest incidence occurring in those of African American or Asian descent.(1) In order to understand pediatric NS and its ramifications we need to discuss some basic anatomy.
Your kidneys are two bean shaped organs found just below your ribs, lying against your back muscles. The functional unit of your kidneys is called a nephron and is composed of a glomerulus and its associated tubules. The glomerulus is the initial site of filtration. Subsequent reabsorption and filtration occur along different segments of the nephron. Each kidney contains over one million nephrons. These structures play a major role in filtering your blood of normal cellular waste products that if not disposed of can accumulate and lead to life-threatening systemic damage. In addition to these harmful byproducts, some very important small ions and molecules – like glucose, sodium, and potassium – also get through the initial filtration. The kidneys then reabsorb or expel these ions accordingly to maintain their necessary concentration for normal cellular function. In a single day, your kidneys can filter anywhere from 120 to 150 quarts of blood to produce about 1 to 2 quarts of urine. Each kidney is connected to your bladder through tubes called ureters. When you empty your bladder, urine is expelled from the body through your urethra.
In pediatric NS the kidney’s filtration units become damaged, disrupting the normal size and charge selectivity barrier that prevent larger proteins from passing through. Now, instead of allowing only small molecules and ions to get through, larger proteins are also filtered out through the damaged filtration barrier. This damage can be due to circulating disease/immune factors or genetic defects that affect the nephron. The loss of these larger proteins results in the three major clinical features of NS which includes: edema, proteinuria, and hyperlipidemia. Click here to learn more about these key symptoms.
Pediatric NS is broadly classified into three main groups – Primary, Secondary, or Congenital.
Primary NS (PNS) is defined as NS in the absence of an identifiable systemic disease. Over 90% of all NS cases belong to this category. (2) Additionally, several subclassifications exist based on how the kidney tissue looks under the microscope. This includes:
- Focal Segmental Glomerulosclerosis (FSGS) – characterized by the formation of scar tissue in the kidneys.
- Minimal Change Disease (MCD) – Most common form of NS in school-aged children where the glomeruli appear histologically normal, however when examined with higher power microscopy glomerular damage becomes visible.
- Membranous Nephropathy (MN) – histology shows thickening of the glomerular membrane which affect filtration capabilities.
At this point it is not sure if these three categories represent different diseases or demonstrate the progression of one disease.
Secondary NS (SNS) is defined as NS associated with an underlying systemic disease which is responsible for the damaged kidney filtration system. Exposure to certain chemicals like mercury and lithium can also lead to kidney damage. Certain bacterial or viral infections such as Hepatitis B, Hepatitis C, HIV, Syphilis, Malaria, and Toxoplasmosis can all lead to glomerular inflammation resulting in damage to the glomerular filtration system. Other diseases or conditions that can cause NS include: Amyloidosis, Lymphoma, and Lupus. In addition, prolonged use of certain medications such as aspirin, ibuprofen, or other nonsteroidal anti-inflammatory drugs can lead to the development of NS.
Lastly, Congenital/Infantile NS is an autosomal recessive disorder, meaning that in order to be passed down both parents must contain at least one copy of the defective gene. The offspring is then unable to synthesize key proteins responsible for maintaining the glomerular filtration barrier. Studies have found that over 80% of all CNS cases have a mutation in any one of five main genes – NPHS1, NPHS2, NPHS3, WT1, LAMB2. (3) Many infants with CNF are born prematurely (35 to 38 weeks) and develop end-stage renal disease sometime between the ages of three to eight. The severity of the disease depends on which mutation is passed down. Many with a NPHS2 mutation have a milder disease and do not begin to show symptoms until adolescence or young adulthood.
Nephrotic Syndrome (NS), Primary Nephrotic Syndrome (PNS), Secondary Nephrotic Syndrome (SNS), Focal Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD), Membranous Nephropathy (MN)
- Downie ML, Gallibois C, Parekh RS, Noone DG. Nephrotic syndrome in infants and children: Pathophysiology and management. Paediatrics and international child health 2017;37(4):248-258.
- Niaudet, Patrick. (2019). Etiology, clinical manifestations, and diagnosis of nephrotic syndrome in children. T. Mattoo & M. Kim (Eds.) UptoDate. Available from https://www-uptodate-com.ezproxy.med.ucf.edu/contents/etiology-clinical-manifestations-and-diagnosis-of-nephrotic-syndrome-in-children?search=nephrotic%20syndrome%20children§ionRank=2&usage_type=default&anchor=H8&source=machineLearning&selectedTitle=1~150&display_rank=1#H8
- Niaudet, Patrick. (2019) Congenital and infantile nephrotic syndrome. T. Mattoo & M. Kim (Eds.) UptoDate. Available from https://www-uptodate-com.ezproxy.med.ucf.edu/contents/congenital-and-infantile-nephrotic-syndrome?search=pediatric%20nephrotic%20syndrome&source=search_result&selectedTitle=5~150&usage_type=default&display_rank=5#H6