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

 

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

 

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

 

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.

 

Other symptoms

 

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.

References

 

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

 

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.

 

Abbreviations

Nephrotic Syndrome (NS), Primary Nephrotic Syndrome (PNS), Secondary Nephrotic Syndrome (SNS), Focal Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD), Membranous Nephropathy (MN)

 

References

 

1. 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.

 

2. 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&sectionRank=2&usage_type=default&anchor=H8&source=machineLearning&selectedTitle=1~150&display_rank=1#H8

 

3. 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

Three years ago, everything changed for Dawn and Steve Patafie. In 2016, their daughter, Peyton, was diagnosed with Nephrotic Syndrome.

“The doctors told us that her condition was extremely rare,” Dawn recalled.

Peyton responded to steroids on the first try, which ultimately put her into remission for a year and a half.

“At that time, I thought Nephrotic Syndrome was a thing of our past. I never imagine it could slip back into our lives,” Dawn mentioned.

But unfortunately, the Patafie’s nightmare came to life and in February 2018, Peyton experienced her first relapse. Afterwards, she was on and off steroids for over a year.

“It was during those countless relapses that I started to feel helpless. One night when I was unable to sleep, I came across a Facebook group for parents who have children with Nephrotic Syndrome. It was through this group that I learned about NephCure,” Dawn said.

Peyton’s condition is now managed with cyclosporine.

“My daughter was extremely lucky to respond to steroids,” Dawn acknowledged.

Dawn and her husband, Steve, turned their helplessness into a plan of action. The two are now giving back in a big way, dedicating their time and energy to the fight against kidney disease.

Since Peyton and her brother, Rocky, both enjoy playing soccer, the Patafie’s put together the North West Arkansas (NWAR) NephCure Soccer Club. The team of young kidney warriors participate in local soccer tournaments to raise awareness and critical funds for NephCure Kidney International.

“We put the NephCure team together so the kids could continue to play [soccer] in the summer with their friends, while spreading awareness about Nephrotic Syndrome. It seemed like a great way to have the kids involved in raising awareness while doing something they love as well. We educated everyone that joined about NephCure and explained to them why the organization was important to us,” Dawn said.

Her husband Steve added, “It was an awesome feeling listening to 6 and 7-year-olds cheer ‘Go Team NephCure,’ on the sidelines. The kids and parents were all extremely supportive of our cause.”

In addition to managing the NWAR NephCure Soccer Club, Dawn is Arkansas’ patient engagement lead for other parents whose children have a similar diagnosis. That responsibility came along with the opportunity to attend NephCure’s Leadership Summit this past March.

“Since attending the Leadership Summit, I no longer feel alone as we deal with Peyton’s Nephrotic Syndrome. Meeting other parents that are going through the same things with their children was so comforting. I now have a network of people to reach out to that I didn’t even know existed,” she said.

Dawn is also the founder of a Facebook group called ‘Arkansas Parents of Children with Nephrotic Syndrome’ where she establishes a local support system. She even met up with two of the moms in the group this summer.

“We had a blast having our daughters meet. Both moms told me that my daughter was the first person that their child has met that also has Nephrotic Syndrome. This is also the case for my daughter,” Dawn mentioned.

On top of the NWAR soccer team and the NephCure leadership role, Dawn and her family is hoping to start a new NephCure walk in Northwest Arkansas in the spring of 2020.

“I hope that the Nephrotic Syndrome families leave our event feeling a sense of support and community that they may have not realized was around. I hope to spread awareness in our area to people that have never heard of the disease or NephCure before,” Dawn said.

The Patafie’s selflessness incredibly enough doesn’t stop there, they are also NephCure Champions. The program is part of our network of grassroots community fundraisers, who fundraise locally and virtually to help support NephCure’s mission of finding better treatments for protein spilling kidney diseases. You can find their web page at give.nephcure.org/Champions.

Many thanks to Dawn, Steve, Peyton, and Rocky Patafie for their tireless efforts in support of our community.

The objective of our 2019 Clinical Trial Collaborative Meeting was to push treatments for rare, protein-spilling kidney diseases forward.

 

In an effort to find these new potential treatments, approximately 100 of the world’s top glomerular kidney disease researchers, doctors, US government officials, international representatives, patient advocates, and pharmaceutical companies met on June 26, 2019 in Washington, D.C.

 

To kick off the day, a panel of adult patients and patient parents sat in front of industry leaders and succinctly explained their frustrations with the lack of a standard of care, including more children in clinical trials, etc. (These excellent panelists ended their session with a standing ovation from the crowd, by the way)!!

 

We took a look at KidneyHealthGateway.com and other clinical trial education and awareness efforts of ours, and then separated our six work groups into breakout sessions where they discussed the impact and timeline of deliverables to come up with a realistic approach on how to implement these changes; ultimately help recruit for clinical trials.

 

In the afternoon, a panel of international experts informed the audience on how we can build global collaboration outside of the United States. Panelists traveled from as far as the United Kingdom, Italy, France, and Germany.

We concluded the day by devoting time for each of the 6 work groups to present their innovative ideas and encouraged conversation and questions amongst the room to make these deliverables even more focused and implementable.

 

A successful meeting on all accounts; June 26th left many attendees very optimistic and motivated to continue their efforts to increase participation in clinical trials while ultimately helping find new treatments for Nephrotic Syndrome, FSGS, IgAN, and other rare kidney diseases.

 

To keep the patient experience front and center during our Clinical Trial Collaborative Meeting, we wanted patients and their families from across the globe to have the ability to explain their frustrations and let drug makers, researchers, and the FDA know why steroids are simply no longer an option.

 

This video is the compilation of the anecdotes and messages our community responded with, which was played throughout the entire meeting.

A livestream of the entire day can also be found here.

Stage 2 Kidney Disease Life Expectancy

 

A patient enters Stage 2 chronic kidney disease (CKD) when their glomerular filtration rate, or GfR, is reduced to between 60-89% This indicates decreased kidney function and mild kidney damage.

 

Patients with stage 2 CKD are in the relatively early stages of kidney disease, and do not need a kidney dialysis or kidney transplant. Life expectancy for stage 2 kidney disease differs between men and women. In general, 40 year old men with stage 2 kidney disease can expect to live for 30 years after diagnosis, and 40 year old women with stage 2 kidney disease can expect to live 34 years. This of course can vary according the lifestyles and ages of the patients. While there is no cure for Stage 2 CKD, patients can take steps to increase their long term survival rates.

 

Symptoms Of Stage 2 Kidney Disease

 

There may be no noticeable symptoms of stage 2 kidney disease, and no or few noticeable health problems. However, some common symptoms are:

 

• High level of creatinine or urea in the blood
• Presence of protein or blood in the urine
• Presence of damage seen in an MRI or CAT scan
• High blood pressure

How To Extend Life Expectancy For Stage 2 Chronic Kidney Disease (CKD)

 

While there is no cure for Stage 2 CKD, you can slow the progression of the disease. Stage 2 CKD patients are not at risk for any immediate kidney failure, so hemodialysis and kidney transplants are not needed.  

 

Living a healthy lifestyle is the best way to slow the progression of kidney disease. 

 

• Eat a healthy diet full of fruits, vegetables, and whole grains
• Exercise 30 minutes per day, 5 days per week
• Stop the use of any tobacco products
• Limit the intake of sodium and refined sugars
• Limit intake of cholesterol and saturated fats
• Regularly monitor blood pressure

 

Regular visits to the patient’s medical team is also highly recommended.

 

Stage 2 Kidney Disease Diet

 

The diet for stage 2 CKD is not much different from an overall healthy diet. There are a few precautions you should take however.

 

• Increase the amount of fresh foods and decrease the amount of processed foods in your diet
• Limit your salt intake
  • Use different spices in place of salt
  • Avoid frozen foods
  • Avoid canned foods
• Eat heart healthy proteins, such as chicken, fish, and plant based proteins
• Choose foods higher in potassium, such as oranges, potatoes, and whole wheat breads and pastas

 

Stages Of Kidney Disease

 

Kidney disease has five stages, with stage 1 being the least serious and stage 5 being end stage kidney failure.

 

Stages are based on glomerular filtration rate tests that are done 90 days apart. Stage 2 kidney disease is considered mild, with minimal decrease in kidney function. 

 

Once the glomerular filtration rate, or gfr, decreases to less than 59% the patient is considered to be in Stage 3 of chronic kidney disease.

 

At less than 30% function the patient will be in Stage 4 kidney disease. Treatment options include dialysis. At Stage 5 kidney disease, the kidneys have become almost unusable, and a transplant will be needed.

 

Stage 3 Kidney Disease Life Expectancy

 

A patient enters Stage 3 chronic kidney disease (CKD) when their glomerular filtration rate, or GfR, is reduced to between 30-59% This indicates decreased kidney function and moderate kidney damage.

 

Patients with stage 3 CKD are in the relatively early stages of kidney disease, and do not need a kidney dialysis or kidney transplant. Life expectancy for stage 3 kidney disease differs between men and women. In general, 40 year old men with stage 3 kidney disease can expect to live for 24 years after diagnosis, and 40 year old women with stage 3 kidney disease can expect to live 28 years. This of course can vary according the lifestyles and ages of the patients. While there is no cure for Stage 3 CKD, patients can take steps to increase their long term survival rates.

 

Symptoms Of Stage 3 Kidney Disease

 

When a patient moves from Stage 2 to Stage 3 chronic kidney disease (CKD), symptoms and health problems start to become more noticeable.

 

Some of these symptoms include:

 

• Fatigue
• Fluid retention, otherwise known as edema
• Pain in the lower back
• Sleep problems
• Orange, red, or dark colored urine

How To Extend Life Expectancy For Stage 2 Chronic Kidney Disease (CKD)

 

While there is no cure for Stage 3 CKD, medical treatment can slow the progression of the disease. Stage 3 CKD patients are not at risk for any immediate kidney failure, so hemodialysis and kidney transplants are not needed.  

 

Living a healthy lifestyle is the best way to slow the progression of kidney disease. 

 

• Eat a healthy diet full of fruits, vegetables, and whole grains
• Exercise 30 minutes per day, 5 days per week
• Stop the use of any tobacco products
• Limit the intake of sodium and refined sugars
• Limit intake of cholesterol and saturated fats
• Regularly monitor blood pressure

 

The patient’s doctor may also recommend a medications to treat high blood pressure, anemia, edema, and pain.

 

Stage 3 Kidney Disease Diet

 

The diet for stage 3 CKD is not much different from an overall healthy diet. There are a few precautions you should take however.

 

• Increase the amount of fresh foods and decrease the amount of processed foods in your diet
• Limit your salt intake
  • Use different spices in place of salt
  • Avoid frozen foods
  • Avoid canned foods
• Reduce protein intake
• Choose foods higher in potassium, such as oranges, potatoes, and whole wheat breads and pastas

 

Stages Of Kidney Disease

 

Kidney disease has five stages, with stage 1 being the least serious and stage 5 being end stage kidney failure.

 

Stages are based on glomerular filtration rate tests that are done 90 days apart. Stage 3 kidney disease is considered moderate, with a noticeable decrease in kidney function. 

 

Once the glomerular filtration rate, or gfr, decreases to less than 30% the patient is considered to be in Stage 4 of chronic kidney disease.

 

At less than 30% function the patient will be in Stage 4 kidney disease. Treatment options include dialysis. At Stage 5 kidney disease, the kidneys have become almost unusable, and a transplant will be needed.

 

Stage 4 Kidney Disease Life Expectancy

 

A patient enters Stage 3 chronic kidney disease (CKD) when their glomerular filtration rate, or GfR, is reduced to between 15-30% This indicates decreased kidney function and severe kidney damage. Stage 4 is the last stage before kidney failure

 

Patients with stage 4 CKD are in the start of end stage kidney disease, and may need dialysis. Patients should also start discussing the possibility of a kidney transplant with their doctor. Life expectancy for stage 4 kidney disease differs between men and women. In general, 40 year old men with stage 4 kidney disease can expect to live for 14 years after diagnosis, and 40 year old women with stage 4 kidney disease can expect to live 16 years. This of course can vary according the lifestyles and ages of the patients. While there is no cure for Stage 4 CKD, patients can take steps to increase their long term survival rates.

 

Symptoms Of Stage 4 Kidney Disease

 

When a patient moves from Stage 3 to Stage 4 chronic kidney disease (CKD), symptoms and health problems start to become more noticeable.

 

Some of these symptoms include:

 

• Fatigue
• Fluid retention, otherwise known as edema
• Pain in the lower back
• Sleep problems
• Orange, red, or dark colored urine
• Increased urination
• Bone disease

How To Extend Life Expectancy For Stage 4 Chronic Kidney Disease (CKD)

 

While there is no cure for Stage 4 CKD, medical treatment can slow the progression of the disease. Stage 4 CKD is the last stage before complete kidney failure, so patients may need to talk to their doctor about dialysis or a complete kidney transplant.

 

Living a healthy lifestyle is the best way to slow the progression of kidney disease. 

 

• Eat a healthy diet full of fruits, vegetables, and whole grains
• Exercise 30 minutes per day, 5 days per week
• Stop the use of any tobacco products
• Limit the intake of sodium and refined sugars
• Limit intake of cholesterol and saturated fats
• Limit intake of protein
• Regularly monitor blood pressure

 

The patient’s doctor may also recommend a medications to treat high blood pressure, anemia, edema, and pain.

 

Stage 4 Kidney Disease Diet

 

The diet for stage 4 CKD is not much different from an overall healthy diet. There are a few precautions you should take however.

 

• Increase the amount of fresh foods and decrease the amount of processed foods in your diet
• Limit your salt intake
  • Use different spices in place of salt
  • Avoid frozen foods
  • Avoid canned foods
• Reduce protein intake
• Choose foods higher in potassium, such as oranges, potatoes, and whole wheat breads and pastas

 

Stages Of Kidney Disease

 

Kidney disease has five stages, with stage 1 being the least serious and stage 5 being end stage kidney failure.

 

Stages are based on glomerular filtration rate tests that are done 90 days apart. Stage 4 kidney disease is the last stage before kidney failure. 

 

Once the glomerular filtration rate, or gfr, decreases to less than 15% the patient is considered to be in Stage 5 of chronic kidney disease.

 

At less than 30% function the patient will be in Stage 4 kidney disease. Treatment options include dialysis. At Stage 5 kidney disease, the kidneys have become almost unusable, and a transplant will be needed.