Key Facts. About C3 Glomerulopathy or C3G 4 WHAT CAUSES C3G? 6 HOW COMMON IS C3G? 7 WHO IS AFFECTED? 9 SIGNS AND SYMPTOMS 12 KIDNEY BIOPSY
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1 WHAT IS CG? BREAKING DOWN THE TERM CG HOW YOUR KIDNEYS WORK WHAT CAUSES CG? WHAT IS THE COMPLEMENT SYSTEM? HOW COMMON IS CG? WHO IS AFFECTED? RELATIONSHIP OF MPGN TYPES I, II, III AND CG SIGNS AND SYMPTOMS TESTS THAT ASSESS THE HEALTH OF THE KIDNEYS COMPLEMENT SYSTEM TESTS KIDNEY BIOPSY Key Facts About C Glomerulopathy or CG
2 What Is CG? C glomerulopathy (glo-mer-u-lop-ah-the) or CG is a rare, chronic disease in which experts believe that a specific part of the immune system, the alternative pathway of the complement system, is not well controlled, often resulting in damage to the kidneys. LET S DIVE DEEPER
3 Breaking Down the Term CG C Glomerulopathy A key protein in the complement system, which is part of the immune system. Problems in the glomeruli, the small units in the kidneys that filter blood. CG WAS IDENTIFIED AS ITS OWN DISEASE IN 0 AND THERE ARE SUBTYPES:. Dense deposit disease or DDD. C glomerulonephritis (glo-mer-u-lo-nah-fri-tis) or CGN DISCOVER HOW YOUR KIDNEYS WORK
4 How Your Kidneys Work Glomeruli Waste and extra water into urine Nephron Unfiltered blood in Filtered blood out Urine out Each kidney has nearly a million workhorses known as nephrons. Each of these nephrons has filtering units called glomeruli (glo-mer-u-lie). Blood enters these glomeruli and gets filtered to form urine, keeping the body in balance. When your kidneys don t work properly, waste and fluid can build up in the body causing serious signs and symptoms. WHAT CAUSES CG?
5 What Causes CG? Research indicates that a loss of control of the alternative pathway of the complement system may be the primary cause of CG. WHAT IS THE COMPLEMENT SYSTEM?
6 What Is the Complement System? The complement system is part of our body s immune system. It is made up of a group of more than 0 circulating proteins that work to protect the body from threats like bacteria and viruses. There are distinct parts or pathways of the complement system the classical, lectin, and alternative pathways. Classical and Lectin Pathways The body turns the classical and lectin pathways on to deal with threats like bacteria. When the threat is gone, the body turns these pathways off. Bacteria Invade Loss of Control Bacteria Cleared OFF Alternative Pathway CG ON The alternative pathway is always on and helping to deal with potential threats, but the body controls it to keep it running at a healthy level. In CG, experts believe that the body loses control of the alternative pathway, leading to overactivity and often resulting in damage to the kidneys. HOW COMMON IS CG?
7 Q: How Common Is CG? A: CG is not common at all. In fact, it s a rare disease. A rare disease is a condition that affects a small percentage of the population. In the United States it is defined as a condition affecting fewer than 00,000 people, while in Europe, it is defined as a condition affecting fewer than in,000 people. to individuals per million people worldwide are affected by CG, with approximately,000 people in the United States There is nearly person with DDD to every people with CGN. DDD CGN WHO IS AFFECTED?
8 Who Is Affected by CG? Males and females are affected equally. People with DDD are more likely to be affected as children or teenagers. People with CGN are more likely to be affected as adults. RELATIONSHIP OF MPGN TYPES I, II, III, AND CG
9 Understanding the Relationship of MPGN Types I, II, III and CG In 0, doctors and experts created a new classification to identify CG as its own disease. This change was made in order to reflect an improved understanding of the cause of disease. Currently, it includes two subtypes DDD and CGN. If you were diagnosed prior to 0, you may have been told you had membranoproliferative glomerulonephritis (mem-bray-no-prah-lif-er-ah-tiv glo-mer-u-lo-nah-fri-tis) or MPGN Types I, II, or III. These are older terms that do not account for what may be causing the disease. 0 MPGN Type I MPGN Type II 0% 0% CG CG MPGN Type III CG 0% If you have been diagnosed with MPGN Type I, II, or III, you may actually have a type of CG. Most patients with an MPGN Type II diagnosis have DDD. While some patients with MPGN Type I or III diagnoses may actually have CGN. It is important to discuss your diagnosis with your healthcare team. WHAT SIGNS AND SYMPTOMS SHOULD I LOOK FOR?
10 Signs and Symptoms Some may be more noticeable than others, but it s important to consider these signs and symptoms: Hematuria (HEME-ah-TOO-ree-ah) or blood in the urine: urine color may look pink, red, or cola-colored when visiting the bathroom Proteinuria (PRO-tee-NEW-ree-ah), meaning high protein levels in the urine: dark foamy urine that may also look cloudy during visits to the bathroom Reduced amounts of urine: less bathroom visits or producing less urine during those visits Edema (ah-deem-ah) or swelling: fluid may build up under the skin in different areas (eg, face, legs, and feet/ankles) High blood pressure: the force of the blood flowing through the body may be too high Decreased general alertness: feeling less focused or aware. It also may be more difficult to concentrate Fatigue or discomfort (malaise): feeling more tired or having general feelings of discomfort Each patient s journey with CG may be different. In some patients, signs, symptoms, and kidney function may get worse over time, as the kidneys are not able to filter fluids and waste from the body. Dense Deposit Disease-Specific Conditions There are some additional signs, symptoms, and conditions that affect people with DDD: Lipodystrophy (LIP-o-DIS-trah-fee): lack of fatty tissue under the skin in the upper part of the body Drusen (DROO-zehn): buildup of deposits at the back of the eye which may cause vision problems CAN TESTS ASSESS THE HEALTH OF MY KIDNEYS?
11 Testing There are several tests that assess the health of the kidneys as well as check different parts of the complement system. The results of these tests may indicate to your doctor if further testing should be considered. WHAT ARE THE ACTUAL TESTS?
12 How do healthy kidneys work? Key Tests That Assess the Health of the Kidneys S erum creatinine (SEER-um cree-at-i-nin): the level of creatinine (waste product that comes from muscle) in the blood. Creatinine is a waste product produced by muscle in the body. Protein Creatinine Measured by a blood test I f the kidneys are not working correctly, creatinine is not filtered as well and may build up in the blood e GFR: estimated glomerular filtration rate Protein is recycled back into the blood, without leaking into the urine. Creatinine and protein are transported to the kidneys through the bloodstream. Most of the creatinine is filtered from the blood and passes into the urine. A number (or measure) calculated by doctors to help estimate how well the kidneys are working T he number is calculated based on a person s serum creatinine levels, age, body size, gender, and race P roteinuria: protein in urine M easured by urine test; looking for the amount of protein in urine P rotein may leak into the urine for people with kidney problems What happens when the kidneys aren t working correctly? Protein isn't recycled and leaks into the urine. This is called proteinuria. Creatinine isn't filtered as well and builds up in the blood. If these tests point toward a problem with your kidneys, your doctor may request that you get tests of your complement system and a biopsy of your kidneys. HOW CAN THE COMPLEMENT SYSTEM BE TESTED?
13 Complement System Tests The complement system consists of proteins circulating in the body working to protect you from threats like bacteria and viruses. Because loss of control of the alternative pathway of the complement system may be the basis for CG, there are several tests that check different parts of the complement system, including how the system is controlled by the body: Complement Protein Levels: Measuring the levels of key complement system proteins in the blood may provide information about the activity of the alternative pathway: C and C proteins: Reduced levels of C and normal levels of C in the blood may indicate overactive alternative pathway activity Factor H: Acting as one of the brakes for the complement system, low levels of Factor H may indicate a reduced ability to control or turn down alternative pathway activity Autoantibodies: The complement system is one part of the body s immune system. Antibodies, which are proteins, are another important part of the immune system. Antibodies normally help the immune system defend against harmful threats like bacteria and viruses. However, in some people, the body can also produce abnormal antibodies. Autoantibodies are abnormal antibodies that attack the body s own cells and interfere with the body s ability to control the alternative pathway. C Nephritic Factor: Common in CG patients, this autoantibody can act as a turbocharger to turn up alternative pathway: Approximately 0% of patients with DDD test positive Approximately 0% of patients with CGN test positive Other Autoantibodies: Less common autoantibodies attacking different parts of the alternative pathway may include anti-factor B, anti-factor H, and anti-cb autoantibodies COMPLEMENT SYSTEM (CONT)
14 Complement System Tests Paraproteins: Antibodies that don t attack the body, but may cause the alternative pathway to react as if these paraproteins were threats to the body More commonly found in older adults with CGN Gene Mutations: Genes are inherited from our parents and provide instructions for how the body works. Some genes involved in the control of the alternative pathway may have mistakes in them known as mutations. These mistakes or mutations may make it hard for the body to adequately control alternative pathway activity. About in CG patients are found to have these mistakes, or mutations, associated with this condition These complement system tests are looking for alternative pathway control and overactivity, as well as risk factors associated with CG. WHAT IS A KIDNEY BIOPSY?
15 Kidney Biopsy Biopsy is a standard part of the diagnosis for CG, where a small amount of tissue from a kidney is removed and examined under special microscopes. KIDNEY BIOPSY (CONT)
16 Kidney Biopsy There are key ways doctors and researchers will review the biopsy including light microscopy, electron microscopy, and/or immunofluorescence. Each reveals different aspects that help to determine what is happening in the glomeruli, the small units in the kidneys that filter blood. Light microscopy: Microscope used to determine types of injury and inflammation in the glomeruli With immunofluorescence (IM-u-no-flu-RES-ence), or IF, a special stain makes immune system proteins in the glomeruli light up and appear brighter under the microscope, including the C protein of the complement system. C Protein Other Immune System Deposits Electron microscopy: Microscope used to detect any abnormal deposits from the body and their location in the glomeruli Immunofluorescence: Technique to identify the types of abnormal deposits found in the glomeruli Finding predominant C deposits in the glomeruli indicates that the alternative pathway is overactive and helps your healthcare team to confirm a diagnosis of CG. It can be further divided into DDD or CGN based on how it appears: In DDD, C deposits are bunched up in one area of the glomeruli and appear thick. In CGN, C deposits are more spread out and less thick. In those cases in which the deposits don t look like DDD, CGN is assigned as the diagnosis. In some patients, a biopsy may not be possible and the healthcare team may have to rely on other tests to make the diagnosis of CG. It s important to keep these key facts about CG in mind and share them with others.
17 WeCG is a community of people connecting to each other and to information, support, and resources that help to shine the light on C glomerulopathy or CG, sponsored by Achillion Pharmaceuticals, Inc. This information is provided only for the purpose of helping patients and family members better understand certain health conditions. This information is not intended in any way to be a substitute for professional medical advice. Achillion Pharmaceuticals, Inc. is a science-driven, patient-focused company. Our mission is to make life-saving medicines for patients with rare diseases. We are committed to delivering the promise of complement-based therapeutics for a wide variety of diseases. WeCG and Together, we are WeCG are trademarks of Achillion Pharmaceuticals, Inc. 0 Achillion Pharmaceuticals, Inc. ACHC000 Last updated /
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