Rare, protein-spilling kidney diseases are a group of conditions that affect the filtering units of the kidneys and are considered uncommon. These diseases are often caused by immune system dysfunction, genetic mutations, environmental factors or a combination of factors. Sometimes, the cause of the disease is idiopathic or unknown. 

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It is estimated that kidney disease affects 37 million people in the United States alone, and globally 1 in 10 people have some form of kidney disease(1). Chronic kidney disease (CKD) is the general term describing kidneys that are damaged or losing function over time and may not clean the blood as well as healthy kidneys. This can happen all of a sudden or over time. Diabetes and high blood pressure are the two most common forms of CKD in the U.S.(3).

While all kidney diseases can be considered CKD, it is important to differentiate rare kidney diseases (RKD) with other causes because they are often diagnosed differently and can require distinctive treatments.

The Food and Drug Administration (FDA) defines a rare kidney disease as a condition that effects less than 200,000 people in the United States (4). It is estimated that there are 150 different types of RKD that can be inherited or acquired with unknown causes. 

Rare kidney disease patients experience unique challenges in both diagnosis and treatment. For this reason it is important that they receive specialized care from nephrologists who are familiar with your specific RKD. 

Rare, protein spilling kidney diseases are:

  • The most aggressive forms of kidney disease.
  • May lead to kidney failure at higher and faster rates than CKD
  • Often go un-diagnosed or mis-diagnosed for a long period of time which can lead to delayed treatment
  • Have few or no FDA approved treatments
  • Small numbers of affected patients
  • Unidentified causes of disease
  • Lack of appropriate tests to monitor some diseases
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How the Kidneys Work

The kidneys play an important role in the body, acting as the body’s filtering system, to eliminate wastes, drugs, and toxins through the urine. Healthy kidneys filter about half a cup of blood each minute returning most of the water back into your blood and removing the wastes in the form of 1 to 2 quarts of urine per day(2).

The kidneys are a very important organ in the body. They are two bean-shaped organs, each about the size of a fist, located just below the rib cage, one on each side of the spine. 

The kidneys also:

  • Regulate electrolyte (salt) concentration
  • Manage the amount of fluid within the body
  • Help control blood pressure
  • Keep bones healthy by making vitamin d and maintaining levels of calcium and other hormones and minerals.
  • Aid in red blood cell production
  • Help regulate growth in children

Each kidney’s nephrons or functional units contain glomeruli, the filtering units and tubules that collect the waste and remove it in the form of urine. 

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Warning Signs

Rare kidney diseases often have distinct signs and symptoms, and it’s important to note that these can vary depending on the specific type and stage of kidney disease. Some patients may not experience noticeable symptoms, so it is important to see a physician yearly for a physical.

The following are all warning signs that you may be at risk for kidney disease:

  • You have a family history of kidney disease
  • You are experiencing unexplained fatigue
  • Unexplained high blood pressure
  • High levels of protein in the urine during a urinalysis is a serious sign that your kidneys are not functioning properly
  • Protein leaking into the urine can cause your urine to be foamy or frothy
  • Dark, cola colored urine 
  • Swelling in your eye lids, face, groin or extremities called pitting edema
  • Unexplained high cholesterol
  • You may experience joint pain or pain in and around the kidneys 
  • Nausea or loss of appetite
  • Decreased urination or changes in frequency

How RKD Impacts Your Kidneys

Rare protein spilling kidney disease that impact the filtering units or glomeruli of the kidneys are also referred to as glomerular disease (GD). Each kidney contains about 500,000 filtering units which form small balls or capillaries through which the blood is filtered. The main role of the glomerulus is to filter wastes out of the blood stream.

Blood enters the glomerulus through the arteries and travels through several layers of cells in which wastes are excreted through the filtering process and removed from the body in the form of urine through the tubules. The clean blood, including vital proteins are then returned to the bloodstream through another artery (refer to the illustration).

The main filtration of proteins happen through cells called podocytes which are located around the outside the glomeruli. In rare, protein spilling kidney diseases or glomerular diseases the filtering units podocytes lose their shape, this is called podocyte foot process effacement. This causes the filtering slits to malfunction, allowing larger molecules such as protein and other cells that belong in the blood, to leak or escape into the urine. 

Proteinuria is the term used to describe too much protein in the urine. 

Hematuria is the term used to describe blood in the urine.

Over time, podocyte foot process effacement and proteinuria can cause permanent damage to the kidney causing podocyte detachment and scarring. Although each type of RKD have differences, they can all cause protein to spill into the urine and may lead to kidney damage.

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Diagnosing Rare Kidney Disease

Diagnosing RKD often requires specialized medical tests with the collaboration of your primary care physician and an experience nephrologist. If your doctor suspects that you have RKD, they will likely run one or more of the following tests:

  • Urinalysis or 24-hour urine test to check for protein and/or blood in your urine.
  • Blood work to check the levels of protein (albumin) in your blood and also to see how your kidney is functioning.
  • A Biopsy is required to diagnose the specific type of RKD you have. 
  • Genetic testing may provide important diagnostic and treatment information
  • Other tests may include: 
    • Blood Pressure
    • Cholesterol blood tests
    • Kidney ultrasound

It is crucial to receive a quick and accurate diagnosis so your condition can be managed effectively. 

[1] Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2021. Centers for Disease Control and Prevention, US Department of Health and Human Services; 2021. [2] National Institute of Diabetes and Digestive and Kidney Diseases. Your Kidneys & How They Work, 2018. [3] Centers for Disease Control and Prevention. Chronic Kidney Disease Basics, 2022. Centers for Diseas Control and Prevention, US Department of Health and Human Services; 2022. [4]Rare Disease at FDA. What is a rare disease, 2022. Food and Drug Administration; 2022. [5] National Institute of Diabetes and Digestive and Kidney Diseases. Glomerular Disease Primer: The Normal Kidney, 2023. Kidney Disease Section, Jeffrey B. Kopp, M.D.; 2023.

Types of Rare Kidney Disease (RKD)

Dive deeper into understanding what causes the specific type of RKD you or your loved one is affected by. We cover how each type of RKD is diagnosed, potential treatment options, and more.

explore different types of RKD

Newly Diagnosed

Are you just starting out in your RKD journey? For so many people, coping with a recent diagnosis of rare kidney disease means feeling afraid, worried, or even alone. Take back your health and your hope by understanding your disease more in depth. We’ll break down the step-by-step actions to ensure you’re receiving the best care possible. 

I’m newly diagnosed with rkd

Pediatric Care

Is your child affected by RKD? The pediatric diagnostic journey can look different than the adult one for kidney disease. Learn more about the unique challenges and risks associated with pediatric patients, and the treatment options available. 

NephCure Specialists

Do you suspect you may have a RKD? It is important to see a nephrologist who understands how to manage your type of RKD. Learn more about nephrologists who specialize in rare, protein spilling kidney diseases and how to contact them.

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