Symptoms of Nephrotic Syndrome in Children
The three major clinical features seen in children with nephrotic syndrome (NS) include: edema, proteinuria and hyperlipidemia. Symptoms arise due to the increased glomerular permeability of the damaged kidney filtration system.
Edema is an abnormal accumulation of fluid in the body. Normally, this fluid retention does not become detectable until it exceeds 3 to 5 percent of body weight. The first noticeable area of swelling is typically the area around the eyes. The fluid displacement seen with edema is gravity dependent. The initial swelling of the eye tends to go down as the swelling in the extremities increases. One classic sign of increased swelling is when a pit is left on the skin when pressure is applied to swollen areas. This is known as pitting edema and occurs due to the displacement of fluids just underneath the skin. Areas of swelling can shift around the body based on body position. Prolonged periods in reclined positions, such as when sleeping, can cause fluid to pool towards ones back. Children may also experience increased abdominal pain due to bowel wall edema. Fluid build up in the lungs can also occur and cause dyspnea – the feeling that you can’t get enough air in your lungs.
Proteinuria is when urinary protein excretion exceeds 100 mg per day or 4 mg per hour. In childhood NS, this occurs as a result of increased glomerular filtration of macromolecules such as albumin. This increased excretion of albumin directly leads to hypoalbuminemia – another key clinical feature of NS. Hypoalbuminemia is when one has low levels of albumin circulating in their blood. Albumin is the most abundant protein circulating in your blood, and because of this it is the biggest contributor to the oncotic pressure in your blood. Oncotic pressure can be thought of as the pressure that draws fluid from your tissues into the blood. When levels of albumin decrease as in NS, we have a drop in the oncotic pressure in your blood. This leads to fluid being pulled away from your blood and into the tissues and results in edema. Other proteins lost include key anticoagulants, which leads to an increased risk of thrombotic events that prevent the blood from flowing normally through the circulatory system. Chronic loss of iron and iron-storage proteins can cause some patients to develop anemia. Iron is an important mineral required by red blood cells to transport oxygen in your body.
Hyperlipidemia is an elevation in circulating cholesterol, triglycerides and total lipids. This occurs due to the liver’s increased work in order to compensate for the loss of protein. The Liver is the major organ responsible for cholesterol, lipid synthesis as well as synthesis of important blood proteins. The liver recognizes the decreased level of albumin and increases albumin synthesis to compensate. However, at the same time it increases cholesterol and triglycerides. While the liver is increasing the synthesis of lipids and cholesterol, we have urinary loss of important lipid regulatory factors such as High-Density Lipoprotein which normally picks ups triglycerides circulating in your blood stream and helps prevent the buildup of atherosclerotic plaque in your blood vessels. Chronic hyperlipidemia increases the risk of early atherosclerosis.
In addition to increased secretion of albumin, we also see increased immune proteins in the urine due to damages along the nephron that interferes with the reabsorption of these important molecules. Loss of these molecules place children with NS at a higher risk of infection to certain bacteria. The most common types of infection include upper respiratory, urinary tract, and peritonitis. Peritonitis is an inflammation of the tissue that lines the inner wall of the abdomen. This can explain why some children experience recurrent abdominal pain. Serious infections can include sepsis, meningitis, and cellulitis. Sepsis is an overactive immune response which can lead to life threatening organ damage. Meningitis is inflammation of the protective covering of the brain. This can result in increased pressure place on the brain and can cause headache, stiff neck, and light sensitivity. Cellulitis is a bacterial skin infection that causes the affected skin to become swollen, red, warm and painful to the touch. If left untreated, the infection could spread to your bloodstream and become potentially life-threatening.
Additionally, despite the increased fluid retention associated with NS, children may experience low blood pressure due to a low effective circulating volume. Although there is a fluid overload most of that fluid is not in your circulatory system. As such, the heart tends to compensate by beating faster to try and circulate more blood.
Niaudet, Patrick. (2019). Complications of Nephrotic Syndrome in Children. T. Mattoo & M. Kim (Eds.) UptoDate. Available from https://www-uptodate-com.ezproxy.med.ucf.edu/contents/complications-of-nephrotic-syndrome-in-children?search=pediatric%20nephrotic%20syndrome&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3#H8