new research on polycystic kidney disease

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A new drug candidate can shrink kidney cysts

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Autosomal dominant polycystic kidney disease (ADPKD), the most common form of polycystic kidney disease, can lead to kidney enlargement and eventual loss of function. The disease affects more than 12 million people worldwide, and many patients end up needing dialysis or a kidney transplant by the time they reach their 60s.

Researchers at MIT and Yale University School of Medicine have now found that a compound originally developed as a potential cancer treatment holds promise for treating ADPKD. The drug works by exploiting kidney cyst cells’ vulnerability to oxidative stress — a state of imbalance between damaging free radicals and beneficial antioxidants.

In a study employing two mouse models of the disease, the researchers found that the drug dramatically shrank kidney cysts without harming healthy kidney cells.

“We really believe this has potential to impact the field and provide a different treatment paradigm for this important disease,” says Bogdan Fedeles, a research scientist and program manager in MIT’s Center for Environmental Health Sciences and the lead author of the study, which appears this week in the Proceedings of the National Academy of Sciences .

John Essigmann, the William R. and Betsy P. Leitch Professor of Biological Engineering and Chemistry at MIT; Sorin Fedeles, executive director of the Polycystic Kidney Disease Outcomes Consortium and assistant professor (adjunct) at Yale University School of Medicine; and Stefan Somlo, the C.N.H. Long Professor of Medicine and Genetics and chief of nephrology at Yale University School of Medicine, are the senior authors of the paper .

Cells under stress

ADPKD typically progresses slowly. Often diagnosed when patients are in their 30s, it usually doesn’t cause serious impairment of kidney function until patients reach their 60s. The only drug that is FDA-approved to treat the disease, tolvaptan, slows growth of the cysts but has side effects that include frequent urination and possible liver damage.

Essigmann’s lab did not originally set out to study PKD; the new study grew out of work on potential new drugs for cancer. Nearly 25 years ago, MIT research scientist Robert Croy, also an author of the new PNAS study, designed compounds that contain a DNA-damaging agent known as an aniline mustard, which can induce cell death in cancer cells.

In the mid 2000s, Fedeles, then a grad student in Essigmann’s lab, along with Essigmann and Croy, discovered that in addition to damaging DNA, these compounds also induce oxidative stress by interfering with mitochondria — the organelles that generate energy for cells.

Tumor cells are already under oxidative stress because of their abnormal metabolism. When they are treated with these compounds, known as 11beta compounds, the additional disruption helps to kill the cells. In a study published in 2011, Fedeles reported that treatment with 11beta compounds significantly suppressed the growth of prostate tumors implanted in mice.

A conversation with his brother, Sorin Fedeles, who studies polycystic kidney disease, led the pair to theorize that these compounds might also be good candidates for treating kidney cysts. At the time, research in ADPKD was beginning to suggest that kidney cyst cells also experience oxidative stress, due to an abnormal metabolism that resembles that of cancer cells.

“We were talking about a mechanism of what would be a good drug for polycystic kidney disease, and we had this intuition that the compounds that I was working with might actually have an impact in ADPKD,” Bogdan Fedeles says.

The 11beta compounds work by disrupting the mitochondria’s ability to generate ATP (the molecules that cells use to store energy), as well as a cofactor known as NADPH, which can act as an antioxidant to help cells neutralize damaging free radicals. Tumor cells and kidney cyst cells tend to produce increased levels of free radicals because of the oxidative stress they’re under. When these cells are treated with 11beta compounds, the extra oxidative stress, including the further depletion of NADPH, pushes the cells over the edge. 

“A little bit of oxidative stress is OK, but the cystic cells have a low threshold for tolerating it. Whereas normal cells survive treatment, the cystic cells will die because they exceed the threshold,” Essigmann says.

Shrinking cysts

Using two different mouse models of ADPKD, the researchers showed that 11beta-dichloro could significantly reduce the size of kidney cysts and improve kidney function.

The researchers also synthesized a “defanged” version of the compound called 11beta-dipropyl, which does not include any direct DNA-damaging ability and could potentially be safer for use in humans. They tested this compound in the early-onset model of PKD and found that it was as effective as 11beta-dichloro.

In all of the experiments, healthy kidney cells did not appear to be affected by the treatment. That’s because healthy cells are able to withstand a small increase in oxidative stress, unlike the diseased cells, which are highly susceptible to any new disturbances, the researchers say. In addition to restoring kidney function, the treatment also ameliorated other clinical features of ADPKD; biomarkers for tissue inflammation and fibrosis were decreased in the treated mice compared to the control animals.

The results also suggest that in patients, treatment with 11beta compounds once every few months, or even once a year, could significantly delay disease progression, and thus avoid the need for continuous, burdensome antiproliferative therapies such as tolvaptan.

“Based on what we know about the cyst growth paradigm, you could in theory treat patients in a pulsatile manner — once a year, or perhaps even less often — and have a meaningful impact on total kidney volume and kidney function,” Sorin Fedeles says.

The researchers now hope to run further tests on 11beta-dipropyl, as well as develop ways to produce it on a larger scale. They also plan to explore related compounds that could be good drug candidates for PKD.

Other MIT authors who contributed to this work include Research Scientist Nina Gubina, former postdoc Sakunchai Khumsubdee, former postdoc Denise Andrade, and former undergraduates Sally S. Liu ’20 and co-op student Jake Campolo. The research was funded by the PKD Foundation, the U.S. Department of Defense, the National Institutes of Health, and the National Institute of Environmental Health Sciences through the Center for Environmental Health Sciences at MIT.

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ADPKD is Reversible in Preclinical Models, Finds New Yale Study

Autosomal dominant polycystic kidney disease (ADPKD), a genetic disorder, causes fluid-filled cysts to develop on the kidneys, which can impair their function. As part of the growth of cysts, the kidneys develop inflammation and fibrosis, or scarring. The disease is most often caused by a mutation in one of two genes, PKD1 or PKD2 , which can be passed down within families, from parent to child.

Working in mice models, Stefan Somlo, MD , C. N. H. Long Professor of Medicine (Nephrology) and Professor of Genetics; chief, Section of Nephrology, and his research team, published a study in Nature Genetics showing that the damage caused by ADPKD can be reversed, demonstrating the surprising plasticity of the kidney.

First, they created a mouse model that allowed inactivation followed by reactivation at a later time of PKD2 . “Essentially, the mouse developed polycystic kidney disease and then we did “gene” therapy, turning on the same gene, a copy, that had been turned off to cause the disease,” said Somlo.

They started with PKD2 , and found that the kidney size shrunk, cysts resolved, and the tubules regained their natural form. In addition, secondary damage such as inflammation and fibrosis were substantially reversed. Researchers performed serial MRIs on each mouse to monitor the decrease in kidney size. Based on what they discovered for PKD2 , they repeated the experiment focusing on PKD1 and confirmed their findings.

“ One surprising finding is that this process of the kidney getting cystic and growing and then getting smaller again is actually possible. That's kind of unexpected and interesting, and it begs the question of what the polycystins normally do, because they must be regulating some feature of tubules getting bigger and smaller to accommodate maybe different physiologic conditions in normal states,” said Somlo.

The researchers concluded that the re-expression of polycystins reversed alterations in cell shape and proliferation, along with inflammation and fibrosis. They found that a potentially regenerative process, autophagy, was activated as the kidneys returned to a more normal state.

Researchers also found that the timing of the therapy was critical. As demonstrated in the study, in later stage ADPKD, while the kidney size and inflammation are reduced, kidney scarring is no longer fully repairable.

The team is evaluating which molecular pathways are activated through the disease reversal, and how they work. They will then determine how best to target these pathways for possible treatments for ADPKD.

Somlo began to study ADPKD when he came to Yale School of Medicine (YSM) as a fellow around 1990. At the time, he was interested in the application to kidney disease of an upcoming technology, molecular biology. He started working on the molecular genetic aspects of disease gene identification for ADPKD, and when he established his own lab, continued expanding his studies of the disease.

Somlo is driven to learn more about kidney function and ADPKD. "There is a whole aspect of kidney function that we don't know. Even after more than two decades of research, we still need to figure out what these PKD gene proteins, polycystins, do. And I think that this study tells us that this disease is treatable, and we should try to figure it out. I think the mouse models are actually a very powerful tool toward that end,” said Somlo.

Other authors on the paper are Ke Dong, MD ; Chao Zhang, Ph.D.; Xin Tian, MD ; Daniel Coman, PhD ; Fahmeed Hyder, PhD ; and Ming Ma, Ph.D.

Read “Renal plasticity revealed through reversal of polycystic kidney disease in mice” in Nature Genetics .

Yale’s Section of Nephrology is committed to excellence in patient care, research, and education with the goal for both their faculty and trainees to be national and international leaders in the field of academic nephrology. To learn more about their mission and work, visit Nephrology .

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New 3-D model offers insights into the role of glucose in a deadly kidney disease

A research team supported by the National Institutes of Health has developed a new approach to better understand the biology of polycystic kidney disease (PKD), an often-life-threatening genetic disorder that affects millions worldwide. Scientists combined two ways to model the disorder — organ-in-a-dish and organ-on-a-chip technologies — to show the role of glucose, a sugar commonly found in blood, in forming PKD cysts. The results, reported in Nature Communications , could lead to better ways to test and develop treatments for PKD, and perhaps other diseases.

An organ-in-a-dish, or organoid, is a miniature version of an organ grown in a laboratory dish. It can mimic key features of a human organ’s structure and function. Organs-on-a-chip, or tissue chips, are more complex 3-D models, containing channels and living cells, that aim to mimic organ and tissue structure and environment. NIH’s National Center for Advancing Translational Sciences (NCATS) research programs develop both technologies as human cell – based approaches to study disease and better predict whether drugs will be safe or toxic in humans.

In PKD, tiny tubes (tubules) in the kidneys expand like water balloons, forming sacs of fluid over decades. The sacs, or cysts, eventually crowd out healthy tissue, leading to problems in kidney function and kidney failure. Scientists have identified many of the genes that cause PKD, but much about the disease remains unknown, including how the cysts form.

“We’re able to boil down a complex process of cyst formation in tubules into a process in a petri dish that takes just a few weeks, but there’s been a lack of technologies to study the disease further,” said University of Washington School of Medicine scientist Benjamin Freedman, Ph.D., who led the work. “Animal models are helpful, but translating the results of those studies to peopl has been a challenge.”

Freedman, co-author Jonathan Himmelfarb, M.D., and their Seattle-based colleagues decided to explore combining organoid technology with a tissue-chip platform. Scientists believe that fluid flow is important in the development of cysts, but they had no way of testing the theory in organoids.

“In kidneys, fluid is always going through the tubules; at any given moment the kidneys have about 25% of the body fluid going through them,” Freedman explained. “We can’t reproduce this system in the dish because fluid needs to move through the kidney structures. Using microfluidic technology in tissue chips was a natural next step.”

Freedman’s group showed that exposing the PKD organoid-on-a-chip model to a combination of water, sugar, amino acids and other nutrients caused cysts to expand relatively quickly. They found that the cysts were absorbing glucose and pulling in water from the fluid passing over them, making the cysts grow larger. Although glucose is generally absorbed by the kidneys, glucose absorption has not been connected to cyst formation in PKD.

“It wasn’t a huge surprise that the cysts could absorb glucose, but it was surprising that they were dependent on it. It’s a new way of thinking of how these cysts form,” Freedman said.

The scientists added fluorescent glucose to mice with PKD and found that the mouse cysts also took up the glucose. “We think the tubules are taking in fluid in the mice, just like in the organoids. The kidney gets bigger, and as the tubules widen to accommodate the expansion over time, cysts form,” Freedman said.

Understanding the mechanisms of PKD can point to new ways to treat it. As part of the study, the research team showed that adding compounds that block glucose transport prevented cyst growth. Freedman noted glucose inhibitors are being developed for other types of kidney disease.

“The researchers have shown that simulating fluid flow is essential to making this system more like the environment in the kidney with PKD,” said Danilo Tagle, Ph.D., director of the NCATS Office of Special Initiatives. “Combining the two technologies makes tissue chip technology more adaptable to drug discovery and drug development and allows researchers to take advantage of the strengths of both platforms. This is very promising for studying other diseases in new ways in the future.”

The research was supported by NCATS; the National Institute of Diabetes and Digestive and Kidney Diseases; and the National Heart, Lung, and Blood Institute through NIH grants UG3TR002158, UG3TR003288, UG3TR000504, K01DK102826, R01DK117914, U01DK127553, UC2DK126006, and U01HL152401.

About the National Center for Advancing Translational Sciences (NCATS):  NCATS conducts and supports research on the science and operation of translation — the process by which interventions to improve health are developed and implemented — to allow more treatments to get to more patients more quickly. For more information about how NCATS helps shorten the journey from scientific observation to clinical intervention, visit  https://ncats.nih.gov .

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov .

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Johns hopkins research shows potential for cure for polycystic kidney disease.

Gastroenterologist and genetics researcher  Liudmila Cebotaru  works on gene and drug-based therapies for genetic diseases and is currently developing a treatment for polycystic kidney disease (PKD) — for which there is no known cure. Medical management of the symptoms of PKD is at best difficult, and most often, impossible. Her work shows initial promise.

Up to this point, Cebotaru has devoted much of her career to therapies for cystic fibrosis. She says that, while cystic fibrosis is primarily a lung disease, it has equally dangerous effects on organs of the gastrointestinal tract, such as the intestine, liver and the pancreas.

PKD has similar characteristics. “PKD primarily affects kidneys. But other organs and systems are also implicated. It affects blood vessels, the brain and the heart. And it can lead to polycystic liver disease.” says Cebotaru.

She explains that PKD causes increased blood pressure and can overwhelm the kidneys with cysts.

“At that point, there’s no kidney function at all,” says Cebotaru. “These people will need a transplant.”

Affecting 600,000 Americans, the most common form of PKD is autosomal dominant, meaning that only one defective gene will cause disease if passed to offspring. The disease is usually diagnosed in patients between the ages of 30 and 60, though research indicates that cysts begin forming in the kidneys  in utero .

Cebotaru’s work with CFTR, the chloride channel and membrane protein that causes cystic fibrosis, informed her suspicion that it might also play a role in this kidney disorder. Working both with mice and with 3D models of kidney cysts, Cebotaru found that introducing a specific CFTR corrector slowed cystic growth in the kidneys.

“Our research demonstrates that the corrector, VX-809, reduces cyst growth, both in mice and in 3D models,” she explains. “The mice had better renal function and less cystic growth. The VX-809 also reduced the levels of heat shock proteins in the mouse kidneys, consistent with the restoration of cellular proteostasis.

The research opened a new window into PKD therapeutics by demonstrating how VX-809 can reverse CFTR, so that rather than secreting fluid, it functions in fluid absorption, thereby shrinking cysts and preserving kidney function.

Cebotaru continues her research in hopes of finding a novel therapy or cure for PKD.

“The work has been very encouraging so far,” she says.

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Polycystic kidney

A healthy kidney (left) removes waste from the blood and maintains the body's chemical balance. With polycystic kidney disease (right), fluid-filled sacs called cysts develop in the kidneys. The kidneys grow larger and slowly lose their ability to work as they should.

Polycystic kidney disease (PKD) is a condition in which clusters of cysts grow in the body, mainly in the kidneys. Over time, the cysts may cause the kidneys to get bigger and stop working. PKD is most often passed through families. This is called an inherited condition.

Cysts are round sacs with fluid in them. They are not cancer. In PKD, the cysts vary in size. They can grow very large. Having many cysts or large cysts can damage the kidneys.

Polycystic kidney disease also can cause cysts to grow in the liver, the pancreas and other places in the body. The disease can cause serious complications, including high blood pressure and kidney failure.

PKD varies greatly in how bad it is. It's possible to prevent some complications. Lifestyle changes and treatments might help reduce damage to the kidneys.

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Polycystic kidney disease symptoms can include:

• High blood pressure.
• Belly, side or back pain.
• Blood in the urine.
• A feeling of fullness in the belly.
• Increased size of the belly from enlarged kidneys.
• Kidney stones.
• Kidney failure.
• Urinary tract or kidney infections.

When to see a doctor

People often have polycystic kidney disease for years without knowing it.

If you have some of the symptoms of polycystic kidney disease, see your healthcare professional. If you have a parent, sibling or child with polycystic kidney disease, see your healthcare professional to talk about screening for the condition.

Autosomal dominant inheritance pattern

In an autosomal dominant disorder, the changed gene is a dominant gene. It's located on one of the nonsex chromosomes, called autosomes. Only one changed gene is needed for someone to be affected by this type of condition. A person with an autosomal dominant condition — in this example, the father — has a 50% chance of having an affected child with one changed gene and a 50% chance of having an unaffected child.

Autosomal recessive inheritance pattern

To have an autosomal recessive disorder, you inherit two changed genes, sometimes called mutations. You get one from each parent. Their health is rarely affected because they have only one changed gene. Two carriers have a 25% chance of having an unaffected child with two unaffected genes. They have a 50% chance of having an unaffected child who also is a carrier. They have a 25% chance of having an affected child with two changed genes.

Gene changes cause polycystic kidney disease. Most often, the condition runs in families. Sometimes, a gene change happens on its own in a child. This is known as a spontaneous gene change. Then neither parent has a copy of the changed gene.

There are two main types of polycystic kidney disease. They're caused by different gene changes. The two types of PKD are:

Autosomal dominant polycystic kidney disease (ADPKD). This is the most common type of ongoing kidney disease that's passed through families, also called inherited. Symptoms of ADPKD often start between the ages of 30 and 40.

Only one parent needs to have the condition to pass it to the children. If one parent has ADPKD, each child has a 50% chance of getting the condition. This is the more common type of polycystic kidney disease.

Autosomal recessive polycystic kidney disease (ARPKD). This type is far less common than is ADPKD. The symptoms often appear soon after birth. Sometimes, symptoms don't appear until later in childhood or during the teen years.

Both parents must have gene changes to pass on this form of the condition. If both parents carry a changed gene, each child has a 25% chance of getting the condition.

Risk factors

The biggest risk factor for getting polycystic kidney disease is getting the gene changes that cause the disease from one or both parents.

Complications

Complications linked to polycystic kidney disease include:

• High blood pressure. This is common in polycystic kidney disease. Not treated, high blood pressure can cause more damage to the kidneys and increase the risk of heart disease and strokes.
• Loss of kidney function. The kidneys' losing their ability to do their work is one of the most serious complications of polycystic kidney disease. Nearly half of people with the condition have kidney failure by age 60. But for some people, it starts in the early 30s.
• Pain. It's common to have pain with polycystic kidney disease. Pain often is in the side or back. The pain can come and go or be ongoing. The pain may be linked to bleeding into a cyst, a urinary tract infection, a kidney stone or, less often, cancer.

Cysts in the liver. The older people with polycystic kidney disease get, the more likely it is they'll get cysts in the liver. With cysts, the liver most often keeps working.

Women tend to get larger cysts than do men. Hormones and pregnancies might be part of the reason.

Brain aneurysm. A balloonlike bulge in a blood vessel, called an aneurysm, in the brain can cause bleeding if it bursts. People with polycystic kidney disease have a higher risk of aneurysms. People with a family history of aneurysms seem to be at highest risk.

Ask your healthcare professional if you need screening. If screening doesn't show an aneurysm, your healthcare professional may suggest screening again in a few years. The timing of repeat screening depends on your risk.

• Pregnancy complications. Most people with polycystic kidney disease can have success with pregnancy. But sometimes, they can get a life-threatening condition called preeclampsia during pregnancy. Those most at risk have high blood pressure or a loss of kidney function before they become pregnant.
• Heart valve conditions. As many as 1 in 4 adults with polycystic kidney disease gets mitral valve prolapse. When this happens, the heart valve no longer closes well. This lets blood leak backward.
• Colon conditions. People with polycystic kidney disease may get weaknesses and pouches or sacs called diverticula in the wall of the colon. This condition is called diverticulosis. Diverticula most often don't cause symptoms, but they may bleed or get infected.

If you have polycystic kidney disease and you're thinking about having children, a genetic counselor can help you know your risk of passing the disease to your children.

Keeping your kidneys as healthy as possible may help prevent some of the complications of this disease. It's most important to manage your blood pressure.

Here are some tips for keeping your blood pressure in check:

• Take the blood pressure medicines your healthcare professional prescribes as directed.
• Eat a low-salt diet that has plenty of fruits, vegetables and whole grains.
• Get to and stay at a healthy weight.
• Exercise regularly. Aim for at least 30 minutes of moderate physical activity most days of the week.
• Limit alcohol use.
• Don't smoke.

Polycystic kidney disease care at Mayo Clinic

• Ferri FF. Autosomal dominant polycystic kidney disease (ADPKD). In: Ferri's Clinical Advisor 2024. Elsevier; 2024. https://www.clinicalkey.com. Accessed March 21, 2024.
• AskMayoExpert. Autosomal dominant polycystic kidney disease (ADPKD). Mayo Clinic; 2023.
• Polycystic kidney disease. National Kidney Foundation. https://www.kidney.org/atoz/content/polycystic. Accessed March 21, 2024.
• Chapman AB, et al. Autosomal dominant polycystic kidney disease (ADPKD): Treatment. https://www.uptodate.com/contents/search. Accessed March 21, 2024.
• Elsevier Point of Care. Clinical Overview: Autosomal dominant polycystic kidney disease (ADPKD). https://www.clinicalkey.com. Accessed March 21, 2024.
• Rossetti S, et al. Identification of gene mutations in autosomal dominant polycystic kidney disease through targeted resequencing. Journal of the American Society of Nephrology. 2012; doi:10.1681/ASN.2011101032.
• Ami TR. Allscripts EPSi. Mayo Clinic. March 29, 2024.
• Shoaf SE, et al. Pharmacokinetics and pharmacodynamics of tolvaptan in autosomal dominant polycystic kidney disease: Phase 2 trials for dose selection in the pivotal phase 3 trial. The Journal of Clinical Pharmacology. 2017; doi:10.1002/jcph.880.
• Torres VE, et al. Strategies targeting cAMP signaling in the treatment of polycystic kidney disease. Journal of the American Society of Nephrology. 2014; doi:10.1681/ASN.2013040398.
• Chebib FT, et al. Recent advances in the management of autosomal dominant polycystic kidney disease. Clinical Journal of the American Society of Nephrology. 2018; doi:10.2215/CJN.03960318.
• Chebib FT, et al. A practical guide for treatment of rapidly progressive ADPKD with tolvaptan. Journal of the American Society of Nephrology. 2018; doi:10.1681/ASN.2018060590.
• Chebib FT (expert opinion). Mayo Clinic. April 1, 2024.
• Abrol N, et al. Simultaneous bilateral laparoscopic nephrectomy with kidney transplantation in patients with ESRD due to ADPKD: A single-center experience. American Journal of Transplantation. 2020; doi:10.1111/ajt.16310.
• Find ADPKD care. PKD Foundation. https://pkdcure.org/coe. Accessed March 22, 2024.
• Hogan MC, et al. Somatostatin analog therapy for severe polycystic liver disease: Results after 2 years. Nephrology Dialysis Transplantation. 2012; doi:10.1093/ndt/gfs152.
• Normal and polycystic kidneys

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Data Insights

Polycystic kidney disease drugs in development, 2024.

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The Polycystic Kidney Disease drugs in development market research report provides comprehensive information on the therapeutics under development for Polycystic Kidney Disease, complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA), and molecule type. GlobalData’s report assesses key aspects of the companies and drugs in development for Polycystic Kidney Disease. Buy the report here.

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Chinook therapeutics inc.

The report also covers the descriptive pharmacological action of the therapeutics and the latest news and press releases. Additionally, the report provides an overview of the key players involved in therapeutic development for Polycystic Kidney Disease and features dormant and discontinued products.

GlobalData tracks 56 drugs in development for Polycystic Kidney Disease by 47 companies/universities/institutes. The top development phase for Polycystic Kidney Disease is preclinical with 24 drugs in that stage. The Polycystic Kidney Disease pipeline has 51 drugs in development by companies and five by universities/ institutes. Some of the companies in the Polycystic Kidney Disease pipeline products market are: Chinook Therapeutics , Goldfinch Bio and Healx.

The key targets in the Polycystic Kidney Disease pipeline products market include Adenosine Monophosphate Activated Protein Kinase ([Hydroxymethylglutaryl CoA Reductase (NADPH)] Kinase or AMPK or EC 2.7.11.31), Cystic Fibrosis Transmembrane Conductance Regulator (ATP Binding Cassette Sub Family C Member 7 or Channel Conductance Controlling ATPase Camp Dependent Chloride Channel or ABCC7 or CFTR or EC 5.6.1.6), and Histone Deacetylase 6 (Protein Phosphatase 1 Regulatory Subunit 90 or HDAC6 or EC 3.5.1.98).

The key mechanisms of action in the Polycystic Kidney Disease pipeline product include Adenosine Monophosphate Activated Protein Kinase ([Hydroxymethylglutaryl CoA Reductase (NADPH)] Kinase or AMPK or EC 2.7.11.31) Activator with five drugs in Preclinical. The Polycystic Kidney Disease pipeline products include eight routes of administration with the top ROA being Oral and eight key molecule types in the Polycystic Kidney Disease pipeline products market including Small Molecule, and Monoclonal Antibody.

Polycystic Kidney Disease overview

Polycystic kidney disease (PKD) is a disorder in which clusters of cysts develop primarily within kidneys. PKD symptoms may include high blood pressure, back or side pain, headache, blood in urine, frequent urination, and kidney failure. The predisposing factors include age and family history. Treatment includes antihypertensive drugs and diuretics.

For a complete picture of Polycystic Kidney Disease’s pipeline drug market, buy the report here.

Blending expert knowledge with cutting-edge technology, GlobalData’s unrivalled proprietary data will enable you to decode what’s happening in your market. You can make better informed decisions and gain a future-proof advantage over your competitors.

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G lobalDat a ,  the leading provider of industry intelligence, provided the underlying data, research, and analysis used to produce this article.

GlobalData’s pipeline drugs offers detailed profiles of pharmaceutical drugs in all stages of pre-clinical and clinical development, from discovery through to pre-registration. Coverage is limited to novel human medicinal drugs and biosimilars seeking market approval proprietary and is one of two primary repositories of pharmaceutical drug information offered by GlobalData through its  Pharmaceutical Intelligence Center .  

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Kidney Disease: Fact Sheet

Table of contents, fast facts (2024 update), what is kidney disease (updated 5/24/2022), what causes kidney disease, how is kidney disease treated, how many people require dialysis or transplant, who is at risk for kidney disease, what's behind racial disparities in kidney disease, how are children and adolescents affected by kidney disease, what are the costs to treat kidney disease, how do you prevent kidney disease, downloadable pdf, kidney disease, also known as “chronic kidney disease (ckd),” causes more deaths each year than breast cancer or prostate cancer. it is the under-recognized public health crisis..

American Cancer Society (ACS). Key Statistics for Breast Cancer in Men. Last Revised January 19, 2024. https://www.cancer.org/cancer/types/breast-cancer-in-men/about/key-statistics.html [“About 530 men will die from breast cancer.”] Centers for Disease Control and Prevention. U.S. Cancer Statistics Female Breast Cancer Stat Bite . U.S. Department of Health and Human Services; 2024. Published June 13, 2024. https://www.cdc.gov/united-states-cancer-statistics/publications/breast-cancer-stat-bite.html [“…in 2022, 42,211 females died from breast cancer.”] Centers for Disease Control and Prevention (CDC). U.S. Cancer Statistics Prostate Cancer Stat Bite . U.S. Department of Health and Human Services; 2023. Published June 13, 2024. https://www.cdc.gov/united-states-cancer-statistics/publications/prostate-cancer-stat-bite.html [“…in 2022, 33,363 males died from prostate cancer”] Leading Causes of Death. Centers for Disease Control and Prevention (CDC); National Center for Health Statistics. Last Reviewed: May 2, 2024. https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm [#9 Nephritis, nephrotic syndrome, and nephrosis: 57,937] Polkinghorne KR. ESKD or cancer: given the choice, which would you rather have? AJKD. 2019 April 22;73(6):753-755. doi: https://doi.org/10.1053/j.ajkd.2019.01.037 https://www.ajkd.org/article/S0272-6386(19)30169-6/fulltext

About 35.5 million U.S. adults are estimated to have kidney disease—that’s more than 1 in 7 (14%).

Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2023 . Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2023. https://www.cdc.gov/kidney-disease/php/data-research/index.html https://www.cdc.gov/kidney-disease/media/pdfs/CKD-Factsheet-H.pdf United States Renal Data System. 2023 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2023. https://usrds-adr.niddk.nih.gov/2023/chronic-kidney-disease/1-ckd-in-the-general-population [Chronic Kidney Disease: Chapter 1 CKD in the General Population; Highlights Bullet #1]

About 9 in 10 adults with kidney disease (≈90%) do not know they have it.

Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2023. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2023. https://www.cdc.gov/kidney-disease/php/data-research/index.html https://www.cdc.gov/kidney-disease/media/pdfs/CKD-Factsheet-H.pdf

People with kidney disease may not feel ill or notice symptoms until the disease is advanced.

About 1 in 3 (40%) of adults with severe kidney disease* don’t know they have it..

*(Stage 4-5; eGFR Stages of Chronic Kidney Disease (CKD). National Kidney Foundation. https://www.kidney.org/atoz/content/stages-chronic-kidney-disease-ckd Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2023. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2023. https://www.cdc.gov/kidney-disease/php/data-research/index.html https://www.cdc.gov/kidney-disease/media/pdfs/CKD-Factsheet-H.pdf Chronic Kidney Disease Basics. Centers for Disease Control and Prevention. Published February 1, 2024. https://www.cdc.gov/kidney-disease/about/index.html

1 in 3 adults in the U.S. (33%) is at risk for kidney disease.

NOTE: Estimate of 1 in 3 (approx. 86 million) adults at risk for CKD is based on U.S. prevalence of diabetes, hypertension, and obesity. Without proper treatment, 1 in 3 will develop CKD. Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2023. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2023. https://www.cdc.gov/kidney-disease/php/data-research/index.html https://www.cdc.gov/kidney-disease/media/pdfs/CKD-Factsheet-H.pdf

Kidney disease is the 8th leading cause of death in the U.S.

Ahmad FB, Cisewski JA, Anderson RN. Mortality in the United States — Provisional Data, 2023. MMWR Morb Mortal Wkly Rep. 2024;73:677–681. DOI: http://dx.doi.org/10.15585/mmwr.mm7331a1 https://www.cdc.gov/mmwr/volumes/73/wr/mm7331a1.htm Rahhal N. CDC reveals leading causes of death for the past 5 years. Here are 5 key takeaways. Yahoo Life. August 8, 2024. Accessed August 8, 2024. https://www.yahoo.com/lifestyle/cdc-reveals-leading-causes-of-death-for-the-past-5-years-here-are-5-key-takeaways-171231678.html

About 1 in 3 adults with diabetes and 1 in 5 adults with high blood pressure may have kidney disease.

Diabetes is the most common cause of kidney disease. diabetes and hypertension cause or contribute to 2 of 3 new cases of kidney failure..

A to Z Health Guide: Chronic Kidney Disease (CKD). Kidney.org. Accessed February 12, 2024. https://www.kidney.org/atoz/content/about-chronic-kidney-disease#about-chronic-kidney-disease-ckd A to Z Health Guide: Diabetes - A Major Risk Factor for Kidney Disease. Kidney.org. Accessed August 2, 2024. https://www.kidney.org/atoz/content/diabetes Causes of Chronic Kidney Disease. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Last Reviewed October 2016. Accessed May 20, 2024. https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/causes Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2023: Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2023. https://www.cdc.gov/kidney-disease/php/data-research/index.html https://www.cdc.gov/kidney-disease/media/pdfs/CKD-Factsheet-H.pdf Chronic Kidney Disease Basics. Centers for Disease Control and Prevention. Published February 1, 2024. https://www.cdc.gov/kidney-disease/about/index.html High Blood Pressure and Kidney Disease. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Last Reviewed March 2020. Accessed May 20, 2024. https://www.niddk.nih.gov/health-information/kidney-disease/high-blood-pressure Kidney Disease Statistics for the United States: Fast Facts on Kidney Disease. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Last reviewed May 2023. Accessed May 20, 2024. https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease [data source CDC 2021] Risk Factors for Chronic Kidney Disease. Centers for Disease Control and Prevention. Accessed August 2, 2024. https://www.cdc.gov/kidney-disease/risk-factors/index.html

Two simple tests (blood/urine) can detect kidney disease early. Earliest detection is crucial so that further damage can be slowed or stopped.

A to Z Health Guide: Chronic Kidney Disease (CKD). Kidney.org. Accessed May 20, 2024. https://www.kidney.org/atoz/content/about-chronic-kidney-disease#about-chronic-kidney-disease-ckd [See: "Diagnosis"]

12 people die every day while on a waiting list for a kidney transplant.

Lentine KL, Smith JM, Lyden GR, Miller JM, Dolan TG, Bradbrook K, Larkin L, Temple K, Handarova DK, Weiss S, Israni AK, Snyder JJ. OPTN/SRTR 2022 Annual Data Report: Kidney. Am J Transplant . 2024 Feb;24(2S1):S19-S118. doi: 10.1016/j.ajt.2024.01.012. PMID: 38431360. https://www.amjtransplant.org/article/S1600-6135(24)00077-7/fulltext [See “Graphical abstract”: https://www.amjtransplant.org/cms/attachment/2acafeda-7d4c-4ee8-9ab4-5a1f05640cff/ga1_lrg.jpg ] Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2022 Annual Data Report. U.S. Department of Health and Human Services, Health Resources and Services Administration; 2024. Accessed May 20, 2024. http://srtr.transplant.hrsa.gov/annual_reports/Default.aspx https://srtr.transplant.hrsa.gov/annual_reports/2022_ADR_Preview.aspx [OPTN/SRTR 2022 Annual Data Report: Kidney; Section 2 Adult Kidney Transplant; 2.1 Waiting List: “There were 4,454 waitlist removals due to death in 2022…” https://srtr.transplant.hrsa.gov/annual_reports/2022/Kidney.aspx 4454/365 = 12.20]

Adults with kidney disease are at higher risk of early death.

Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2023. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2023. https://www.cdc.gov/kidney-disease/php/data-research/index.html https://www.cdc.gov/kidney-disease/media/pdfs/CKD-Factsheet-H.pdf [“Adults with kidney disease are at a higher risk of dying earlier than adults of similar age without CKD.”]

Prevalence of kidney disease: non-Hispanic Black adults 20%; Hispanic/Latino adults 14%; non-Hispanic Asian adults 14%; non-Hispanic White adults 12%.

Black/african american people have 4 times the incidence of kidney failure (eskd) as white persons., hispanic/latino and american indian/alaska native people have 2 times the incidence of kidney failure as white persons. asian people are 1.4 times more likely than whites to experience kidney failure..

[References for three facts above.] Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2023. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2023. https://www.cdc.gov/kidney-disease/media/pdfs/CKD-Factsheet-H.pdf [“• Non-Hispanic Black persons have 4 times the incidence rate of ESKD than non-Hispanic White persons. • Hispanic persons have twice the incidence rate of ESKD than non-Hispanic White persons.”] https://www.cdc.gov/kidney-disease/php/data-research/index.html Diabetes and American Indians/Alaska Natives. U.S. Department of Health and Human Services; Office of Minority Health. Accessed: May 22, 2024. https://minorityhealth.hhs.gov/diabetes-and-american-indiansalaska-natives [data source CDC 2021] Kidney Disease Statistics for the United States: Fast Facts on Kidney Disease. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Last reviewed May 2023. Accessed May 20, 2024. https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease [data source CDC 2021] United States Renal Data System. 2023 USRDS Annual Data Report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2023. https://usrds-adr.niddk.nih.gov/2023/end-stage-renal-disease/1-incidence-prevalence-patient-characteristics-and-treatment-modalities [End Stage Renal Disease: Chapter 1 Incidence, Prevalence, Patient Characteristics, and Treatment Modalities: Highlights: Bullet #4: “In 2021, the incidence of ESRD among Black individuals was 3.8 times that of White individuals; the incidence among Native American individuals was 2.3 times as high, and it was twice as high among Hispanic individuals (Figure 1.4). Although these disparities had been improving until 2018, they worsened from 2018 to 2021.”]

30% of all patients with kidney failure are Black/African American, even though this group is 13% of the U.S. population.

Kidney Disease Statistics for the United States: Fast Facts on Kidney Disease. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Last reviewed May 2023. Accessed May 20, 2024. https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease [Data source: CDC 2021]

Almost one-third of people on the kidney transplant waitlist are Black/African American. Black/African American transplant recipients are also less likely to receive a kidney from a living donor.

El-Khoury B, Yang TC. Reviewing racial disparities in living donor kidney transplantation: a socioecological approach. J Racial Ethn Health Disparities. 2024 Apr;11(2):928-937. doi: 10.1007/s40615-023-01573-x. Epub 2023 Mar 29. PMID: 36991297; PMCID: PMC10057682. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057682/ https://link.springer.com/article/10.1007/s40615-023-01573-x Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2022 Annual Data Report. U.S. Department of Health and Human Services, Health Resources and Services Administration; 2024. Accessed May 20, 2024. http://srtr.transplant.hrsa.gov/annual_reports/Default.aspx https://srtr.transplant.hrsa.gov/annual_reports/2022_ADR_Preview.aspx [“Disparities in access to LDKT [living donor kidney transplantation] persist. While 31.7% of adult waitlisted candidates on December 31, 2022, were Black (Table KI 1), Black patients made up only 12.8% of LDKT recipients versus 34.1% of DDKT recipients that year (Table KI 6). White patients made up 35.5% of the waiting list (Table KI 1), while 61.4% of LDKT recipients and 35.3% of DDKT recipients were White (Table KI 6).”] U.S. Department of Health & Human Services (HHS); Health Resources and Services Administration (HRSA); Organ Procurement and Transplantation Network (OPTN). Data & Calculators. Organ Procurement and Transplantation Network (OPTN). Accessed June 21, 2024. https://optn.transplant.hrsa.gov/ [ OPTN Homepage > Tab: Data & calculators > View Data Reports > National Data > Step 1: Choose category: Waiting list; Count: Candidates; Step 2: Choose Organ: Kidney > Step 2: Choose report: Organ by Ethnicity; Change Report: Candidates; Column: Kidney; Rows: Black, Non-Hispanic/All Ethnicities. Results as of 6/21/2024: 26,556/89,414 ]

Approximately 1 in 4 Medicare dollars is spent on kidney patients—$156.7 billion and growing.

National Kidney Foundation Advocacy. “1 in 4 Medicare dollars are spent on…” March 7, 2024. Accessed May 21, 2024. https://x.com/NKF_Advocacy/status/1765882641394675738 United States Renal Data System. 2023 USRDS Annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2023. https://usrds-adr.niddk.nih.gov/2023/chronic-kidney-disease/6-healthcare-expenditures-for-persons-with-ckd [Chronic Kidney Disease: Chapter 6 Healthcare Expenditures for Persons with CKD; Highlights Bullet # 2: “Total Medicare FFS spending for all beneficiaries (both older and younger than age 66, in contrast to above) with CKD was $86.1B in 2021, representing 22.6% of total Medicare FFS expenditures (Tables 6.1 and 6.2).”] https://usrds-adr.niddk.nih.gov/2023/end-stage-renal-disease/9-healthcare-expenditures-for-persons-with-esrd [End Stage Renal Disease: Chapter 9 Healthcare Expenditures for Persons with ESRD; Highlights Bullet #1: “Total inflation-adjusted Medicare expenditures for patients with ESRD increased steadily from $48.1B in 2011 to $53.8B in 2019, fell for the first time in 2020 to $51.6B, and then increased again in 2021 to $52.3B (Figure 9.1). However, with the transition of many Medicare FFS beneficiaries to Medicare Advantage (MA) in 2021, spending for Medicare Advantage, increased from $12.5B to $18.3B , or by 46.4% in a single year.”]

Without increased investment in prevention, the total number of patients with kidney failure (ESKD) will likely exceed 1 million by 2030.

McCullough KP, Morgenstern H, Saran R, Herman WH, Robinson BM. Projecting ESRD incidence and prevalence in the United States through 2030. J Am Soc Nephrol. 2018 Dec;30(1):127–135. ASN.2018050531 doi: 10.1681/ASN.2018050531. Epub 2018 Dec 17. PMID: 30559143; PMCID: PMC6317596. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317596/ https://www.researchgate.net/publication/329721173_Projecting_ESRD_Incidence_and_Prevalence_in_the_United_States_through_2030 [“Conclusions: The burden of ESRD will increase in the United States population through 2030 due to demographic, clinical, and lifestyle shifts in the population and improvements in RRT. Planning for ESRD resource allocation should allow for substantial continued growth in the population of patients with ESRD. Future interventions should be directed to preventing the progression of CKD to kidney failure.”] Murray R, Zimmerman T, Agarwal A, Palevsky PM, Quaggin S, Rosas SE, Kramer H. Kidney-related research in the United States: a position statement from the National Kidney Foundation and the American Society of Nephrology. Am J Kidney Dis. 2021 Aug;78(2):161-167. doi: 10.1053/j.ajkd.2021.04.006. Epub 2021 May 11. PMID: 33984405; PMCID: PMC10718284. https://www.ajkd.org/article/S0272-6386(21)00594-1/fulltext https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10718284/ https://pubmed.ncbi.nlm.nih.gov/33984405/

COVID-19 continues to endanger the health and lives of kidney patients. The CDC recently (2/2024) updated their guidelines to recommend that people 65 and older should get vaccine boosters.

Centers for Disease Control and Prevention. CDC updates and simplifies respiratory virus recommendations (press release). March 1, 2024. https://www.cdc.gov/media/releases/2024/p0301-respiratory-virus.html https://www.cdc.gov/coronavirus/2019-nCoV/index.html Del Vecchio L, Balafa O, Dounousi E, Ekart R, Fernandez BF, Mark PB, Sarafidis P, Valdivielso JM, Ferro CJ, Mallamaci F. COVID-19 and cardiovascular disease in patients with chronic kidney disease. Nephrol Dial Transplant. 2024 Jan 31;39(2):177-189. doi: 10.1093/ndt/gfad170. PMID: 37771078; PMCID: PMC10828215. https://academic.oup.com/ndt/article/39/2/177/7285814 https://pubmed.ncbi.nlm.nih.gov/37771078/ Geetha, D., Kronbichler, A., Rutter, M. et al. Impact of the COVID-19 pandemic on the kidney community: lessons learned and future directions. Nat Rev Nephrol. 18, 724–737 (2022). https://doi.org/10.1038/s41581-022-00618-4 https://www.nature.com/articles/s41581-022-00618-4 Hartmann-Boyce J. The disproportionate toll that COVID-19 took on people with diabetes continues today. The Conversation. June 6, 2024. https://theconversation.com/the-disproportionate-toll-that-covid-19-took-on-people-with-diabetes-continues-today-227314 Whyte LE. U.S. tries to be clearer on who should get covid booster: the CDC says people 65 and older should get shots this spring, stronger language than the agency had used. Wall Street Journal. February. 28, 2024. https://www.wsj.com/health/healthcare/cdc-advisers-try-to-be-clearer-on-who-should-get-covid-booster-a95d0450 [Quoted: “Should.”—Federal vaccine advisers’ guidance on spring Covid-19 boosters for people 65 and older, a stronger recommendation than the CDC’s current language saying older adults “may” get the shots. The agency has to sign off on the tougher guidance, but it usually follows the committee’s advice. Doing so would ensure most health plans cover the inoculations without an out-of-pocket charge. The virus leads to around 20,000 new hospital admissions and 2,000 deaths every week. People 75 years and older die at the highest rate.” — Wall Street Journal email newsletter. February 29, 2024.]

Chronic kidney disease (CKD) means your kidneys are damaged and losing their ability to keep you healthy by filtering your blood. In the early stages of the disease, most people do not have symptoms. But as kidney disease gets worse, wastes can build up in your blood and make you feel sick. You may develop other problems, like high blood pressure, anemia, weak bones, poor nutritional health, and nerve damage. Because kidneys are vital to so many of the body's functions, kidney disease also increases your risk of having heart and blood vessel disease. While these problems may happen slowly and without symptoms, they can lead to kidney failure, which can appear without warning . Once kidneys fail, dialysis or a kidney transplant is needed to stay alive. Kidney failure is also called kidney failure with replacement therapy (KFRT).

The two main causes of kidney disease are diabetes and high blood pressure.

• These two conditions were the primary diagnosis in 76% of kidney failure cases between 2015-2017: 47% of new KFRT patients had a primary diagnosis of diabetes, the leading cause of KFRT, while 29% of new KFRT patients had a primary diagnosis of hypertension, the second leading cause of KFRT.
• Other conditions that can lead to KFRT are: glomerulonephritis (diseases that damage the kidney's filtering units), which are the third most common type of kidney disease; inherited diseases, such as polycystic kidney disease; malformations at birth that occur as a fetus develops; lupus and other immune diseases; obstructions such as kidney stones or an enlarged prostate; and repeated urinary tract infections, which can also lead to kidney infections and can cause long-term damage to the kidneys.
• People with kidney disease are at greater risk for cardiovascular disease and death at all stages of kidney disease. Kidney disease and heart disease are linked and have common risk factors, such as diabetes and hypertension. Each condition can lead to or worsen the other.

The best treatment of kidney disease is facilitated by early detection , when the disease can be slowed or stopped. Early treatment includes diet, exercise, medications, lifestyle changes, and treating risk factors like diabetes and hypertension. However, once kidneys fail, treatment with dialysis or a kidney transplant is needed.

• Dialysis comes in two forms: hemodialysis (HD) or peritoneal dialysis (PD). Both forms remove wastes and extra fluid from your blood. Patients receive hemodialysis usually 3–4 times a week, either at home or at a dialysis center. During hemodialysis, your blood is pumped through a dialysis machine, where it is cleaned and returned to your body. With peritoneal dialysis, your blood is cleaned inside your body every day through the lining of your abdomen using a special fluid that is periodically changed. Peritoneal dialysis can be done at home, at work, at school, or even during travel. Home dialysis is an increasingly popular mode of treatment, and is associated with better outcomes.
• A kidney transplant places a healthy kidney into your body from a deceased donor or from a living donor, such as a close relative, spouse, friend, or generous stranger. A kidney transplant, however, is a treatment, not a cure. Antirejection and other medications are needed to maintain the transplant. Per the United States Renal Data System (USRDS), more than 22,000 (22,393) kidney transplants were performed in the United States in 2018. The active waiting list remains substantially larger than the supply of donor kidneys, which presents a continuing challenge.
• Although it is very important for patients who are nearing the need for dialysis or kidney transplantation to be cared for by a nephrologist, in 2018, 38.8% of incident (newly occurring) KFRT patients (18–44 years) had received little or no pre-KFRT nephrology care .
• In 2018, 785,883 Americans had kidney failure, and needed dialysis or a kidney transplant to survive (2 in every 1,000 people). 554,038 of these patients received dialysis to replace kidney function and 229,887 lived with a kidney transplant.
• About 130,000 people started KFRT treatment in 2018, of which approximately 128,000 started dialysis as the initial mode of therapy.
• In 2018, 22,393 people received a kidney transplant. By the end of 2018, a total of 229,887 Americans were living with a kidney transplant.
• While about 100,000 Americans are waiting for a kidney transplant, only 22,817 Americans received one in 2020. About one-third of these transplants came from living donors.
• Living and deceased kidney donors are crucial: 12 people die every day while waiting for a kidney transplant.
• In 2016, more than 3,600 kidneys from deceased donors were surgically discarded ; NKF is making efforts to utilize more of these kidneys for transplantation.
• People with kidney disease are five to ten times more likely to die prematurely than they are to progress to KFRT. More than 100,000 people with KFRT died in 2018.
• Without increased investment in prevention, the total number of patients with kidney failure will likely exceed 1 million by 2030.
• 1 in 3 adults in the U.S. is at risk for kidney disease. Some demographic groups are at higher risk. (See " What's Behind Racial Disparities in Kidney Disease? " section.)
• Risk factors for kidney disease include : diabetes; high blood pressure; family history of kidney failure; age 60 or older; obesity; heart disease; past damage to kidneys; and being in minority populations that have high rates of diabetes or high blood pressure, such as Black/African Americans, Hispanics or Latinos, Asian Americans or Pacific Islanders, and American Indians or Alaska Natives (Note: current CDC/ NHANES demographic terminology.).

People from some groups are more likely to develop kidney disease than others. Many factors can contribute to these groups being at higher risk, ranging from societal to medical reasons.

• A breakdown of kidney disease rates within demographic categories of the general population of the United States for 2015—2018 (USRDS, Prevalence of CKD in U.S. adults within age, sex, race/ethnicity, & risk factor categories) showed: 16.0% Non-Hispanic Black/African American; 15.7% Non-Hispanic White; 11.9% Hispanic or Latino (2018).
• Among Medicare FFS (fee-for-service) beneficiaries, kidney disease is highest among Blacks/African Americans (33%) , followed by American Indians or Alaska Natives (30%), Hispanics or Latinos (28%), and Asian Americans or Pacific Islanders (26%). Whites (23%) beneficiaries had the lowest percentages of kidney disease (2018).
• Non-Hispanic Black/African-American and Hispanic or Latino people experience more rapid decline of kidney function than non-Hispanic Whites. Minority communities in general are at increased risk of progressing from CKD to KFRT and of progressing more rapidly.
• Black/African American people are more than 4 times as likely as White people to develop kidney failure . Black/African American people are 13% of the U.S. population, while representing 35% of those with kidney failure.
• Black/African-American race is also associated with increased risk for acute kidney injury (AKI) .
• Black/African Americans also suffer higher rates of comorbid conditions , such as diabetes and high blood pressure, resulting in higher rates of fair/poor health (age 18+, 22% Black/African Americans vs. 16% Whites).
• Compared to non-Hispanics, Hispanics or Latinos are almost 33% (1.3 times) more likely to receive a diagnosis of kidney failure .
• Native Hawaiians, Pacific Islanders, American Indians and Alaska Natives also have a higher prevalence of kidney disease than Whites.
• There are disparities in the quality of primary care for patients of different racial, ethnic, and socioeconomic groups who have kidney disease and kidney disease risk factors. These disparities are related to patient, clinician, clinical, and systemic factors. Patients receiving dialysis in areas with populations that are largely Black/African American, low-income, or of lower educational attainment, are less likely to have received pre-dialysis care from a nephrologist . One study found that 52% of Hispanic or Latino patients on hemodialysis had not received pre-dialysis care from a nephrologist, compared to 44% of non-Hispanic patients.
• Black/African Americans and Hispanics or Latinos are also less likely to be treated with kidney transplantation than Whites.
• On average, Black/African-American transplant candidates wait longer than White transplant candidates for kidney, heart, and lung transplants .
• In 2018, 57% of White patients with KFRT received in-center hemodialysis, versus 72% of Black/African- American patients. This may reflect fewer Black/African-American patients utilizing home dialysis options.

Many children and adolescents have conditions that , if left untreated, dramatically increase their risk for kidney disease and KFRT: about 4% of youths (12–19 yrs) in the U.S. have hypertension, while about 10% have elevated blood pressure. In children aged 2–19 years, the prevalence of obesity is 18.5% (about 13 million), and 210,000 people younger than 20 years are living with diagnosed diabetes. The growing prevalence of these conditions in children means that the incidence and prevalence of kidney disease will likely increase further in the coming years.

• 6,427 children (<18 yrs old) in the U.S. lived with KFRT in 2017.
• According to one study, children with KFRT are 30 times more likely to die prematurely than healthy children. In another study, adolescents (<18 yrs old) with KFRT since childhood had a life expectancy of 38 years if they were treated with dialysis during childhood, and 63 years if they received a kidney transplant during childhood.
• The primary causes of pediatric KFRT in the U.S. between 2015–2018 were: primary glomerular disease, CAKUT (congenital anomalies of the kidney and urinary tract), cystic/hereditary/congenital disorders, and primary/secondary glomerular disease/vasculitis. Urinary tract infections can also lead to kidney infections, which can cause long-term damage to the kidneys.
• In 2020, 710 children (<18 yrs old) received a kidney transplant .
• M ore than 1,000 children (<18 yrs old) are waiting for a donated kidney .
• White children were twice as likely to receive a kidney transplant as Black/African-American children (20.8% versus 10.0%).
• More Black/African-American (57.3%) children than White (40.5%) children-initiated hemodialysis (HD).
• Hispanic or Latino children received a kidney transplant less often than non-Hispanic children (12.0% versus 20.2%) and initiated HD more often and PD less often.
• The median kidney transplant waitlist time for children, by race: 35.2 months for Black/African-American children; 34.0 months for children of other race groups (not Black, White, or Asian); 23.3 months for White children; and 20.3 months for Asian-American children.

In 2018, Medicare costs for all people with all stages of kidney disease were $130 billion. In 2018 Medicare spent $81 billion for people with kidney disease and an additional $49.2 billion for people with KFRT. For 2018, per person per year (PPPY) spending on KFRT patients was $80,426. Early detection of kidney disease could save a substantial percentage of these costs.

• Per type of KFRT treatment, Medicare spent: $93,191 PPPY for HD, $78,741 for PD, and $37,304 for kidney transplant (2018).
• In 2018, Medicare spent an estimated $24,674 PPPY to care for someone with non-KFRT CKD, more than double the spending on the average Medicare beneficiary ($12,899).
• Almost 64.3% of new KFRT patients applied for Medicare (2018).
• In 2018, there were over 500,000 Medicare beneficiaries on maintenance dialysis (about 1% of Medicare fee-for-service population), accounting for 7.2% of the overall claims paid by Medicare.
• Total Medicare Part D spending (2009–2018) rose by 188% for those with CKD ($4.6 to $13.1 billion) and by 37% for those without CKD ($39.5 to $54.2 billion).
• For kidney transplant recipients , Medicare Part B spent $2,453 on immunosuppressive drugs , PPPY (2018).
• Medicare Part D spending was 1.7 times higher for those with CKD ($5392 PPPY) than for those without CKD ($3118 PPPY) (2018).
• Medicare Part D spending was 2.4 times higher for patients with KFRT ($8,173 PPPY) than those without ($3397 PPPY) (2018).
• There is good news, however, for patients burdened with immunosuppressive drug costs when they are no longer covered by the current 36-month limit. The NKF-supported Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act (S. 3353/H.R. 5534) was passed by both the U.S. House of Representatives and U.S. Senate in December 2020. This bill ensures that transplant patients on Medicare will receive lifetime unlimited coverage for immunosuppressive medications. This legislation represents a significant, positive change in the lives of many kidney patients.

However, there is still a lot of work to be done: Minority communities may have less access to healthcare than other Americans. For example, studies found that about one-third of Hispanics or Latinos, 20% Black/African Americans, and nearly 1 out of 3 American Indians and Alaska Natives were uninsured .

Early Detection

Early detection is the most effective way to combat kidney disease. There are two simple, quick, and inexpensive tests for kidney disease:

Keep Kidneys Healthy

• A kidney damage urine albumin-creatinine ratio (uACR) test measures the amount of protein called albumin in your urine. Damaged kidneys leak protein into your urine; it should be in your bloodstream.
• A kidney function blood test, creatinine, is used to measure your glomerular filtration rate (GFR), which tells how well your kidneys are working to remove wastes from your blood. It is the best way to check kidney function.
• People with kidney disease should : •Lower high blood pressure; •Manage blood sugar levels; •Reduce salt intake; •Avoid NSAIDs, a type of painkiller; •Moderate protein consumption; •Get an annual flu shot
• Everyone should : •Exercise regularly; •Control weight; •Follow a balanced diet; •Quit smoking; •Drink alcohol only in moderation; •Stay hydrated; •Monitor cholesterol levels; •Get an annual physical; •Know your family medical history

Preventative Medicine Pays Off

• A recent report from the Centers for Disease Control and Prevention (CDC) states that between 1996 and 2013, there was a 54% decrease in the incidence of diabetes-related KFRT in Native American and Alaska Natives since the Special Diabetes Program for Indians (SDPI) began in 1997. The CDC estimates that the decrease in KFRT related to diabetes resulted in 2,200 to 2,600 fewer cases of diabetes-related KFRT, and estimates $436 to $520 million in savings to Medicare over 10 years.

Download the fully annotated fact sheet to keep this information on hand.

The National Kidney Foundation (NKF) is the largest, most comprehensive, and longstanding patient-centric organization dedicated to the awareness, prevention, and treatment of kidney disease in the U.S.

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Polycystic kidney disease articles within Nature Communications

Article 01 May 2024 | Open Access

Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease

Cyst growth in autosomal dominant polycystic kidney disease (ADPKD) is driven by unknown molecular signals that require the presence of intact primary cilia in the absence of the PKD gene products. Here, the authors show that the transcription factor Glis2 is a key effector of this cilia dependent cyst growth pathway and a potential target for therapy in ADPKD

• , Michael Rehman
•  &  Stefan Somlo

Article 08 January 2024 | Open Access

Deletion of Aurora kinase A prevents the development of polycystic kidney disease in mice

Using different mouse models of Polycystic Kidney Disease, this research demonstrated that deletion of the Aurora Kinase A gene was able to prevent cyst initiation and growth, identifying it as a central regulator of pathogenesis in this condition.

• Ming Shen Tham
• , Denny L. Cottle
•  &  Ian M. Smyth

Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation

A vesicle trafficking Rab11 effector switch is important for ciliogenesis. Here, the authors report a ciliopathy-related disorder caused by variants in WDR44, a Rab11 effector. WDR44 variants show higher affinity for Rab11 and can impair ciliogenesis.

• Andrea Accogli
• , Saurabh Shakya
•  &  Christopher J. Westlake

Article 14 December 2023 | Open Access

Polygenic risk alters the penetrance of monogenic kidney disease

Polygenic factors may partially explain the observed variability in the penetrance of monogenic diseases. Here, the authors show that a polygenic risk score for chronic kidney disease is significantly associated with a higher risk of renal dysfunction in the two most common monogenic forms of kidney disease, suggesting that accounting for polygenic factors improves risk stratification in monogenic kidney disease.

• , Ning Shang
•  &  Krzysztof Kiryluk

Article 16 October 2023 | Open Access

Fibrocystin/Polyductin releases a C-terminal fragment that translocates into mitochondria and suppresses cystogenesis

Fibrocystin/Polyductin (FPC) is a large ciliary membrane protein encoded by PKHD1 which, when mutated, causes ARPKD. Here, the authors show that FPC suppresses cyst development in the kidney of mouse models through the release and mitochondrial translocation of its C terminal product.

• Rebecca V Walker
•  &  Feng Qian

Article 30 March 2023 | Open Access

The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion

Mutations in the gene encoding PC1 cause ADPKD, a common genetic renal disease. Here, the authors show that expression of the C-terminal 200 amino acids of the large PC1 protein in mouse models of ADPKD suppresses cystic disease through an interaction with the mitochondrial enzyme NNT.

• Laura Onuchic
• , Valeria Padovano
•  &  Michael J. Caplan

Article 23 December 2022 | Open Access

Glucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease

In polycystic kidney disease (PKD), fluid-filled cysts arise from tubules. Here the authors show that subjecting organoids to fluid shear stress in a PKD-on-a-chip microphysiological system promotes cyst expansion via an absorptive pathway.

• Sienna R. Li
• , Ramila E. Gulieva
•  &  Benjamin S. Freedman

Article 30 October 2022 | Open Access

Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis

Autosomal dominant polycystic kidney disease (ADPKD) is a complicated disease that involves numerous cell types. Here the authors used a multiomics approach consisting of single nucleus transcriptomes and epigenomes to redefine cell states in ADPKD and to dissect the cellular interactions and molecular mechanisms of ADPKD.

• Yoshiharu Muto
• , Eryn E. Dixon
•  &  Benjamin D. Humphreys

Article 15 August 2022 | Open Access

PKD1 and PKD2 mRNA cis-inhibition drives polycystic kidney disease progression

ADPKD, a common aetiology of kidney failure, is caused by heterozygous PKD1 or PKD2 mutations. Here the authors show that preventing 3′-UTR cis-inhibition of mRNAs produced by the non-inactivated PKD1/2 alleles ameliorates preclinical ADPKD.

• Ronak Lakhia
• , Harini Ramalingam
•  &  Vishal Patel

Article 27 July 2021 | Open Access

Extracellular vesicles and exosomes generated from cystic renal epithelial cells promote cyst growth in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease is characterized by the formation of cysts in the kidney. Here the authors show that cystic extracellular vesicles/exosomes play a critical role in regulating the biology and function of adjacent cells, including renal epithelial cells, fibroblasts and macrophages, and contribute to renal cyst growth.

• , Linda Xiaoyan Li
•  &  Xiaogang Li

Article 28 August 2020 | Open Access

Cyst growth in ADPKD is prevented by pharmacological and genetic inhibition of TMEM16A in vivo

Polycystic kidney disease (PKD) is characterized by the formation of large renal cysts, which lead to a decline in renal function. Here the authors show that genetic and chemical inhibition of TMEM16A largely reduces cyst enlargement in an in vivo model of autosomal dominant PKD.

• Ines Cabrita
• , Andre Kraus
•  &  Björn Buchholz

Article 12 September 2019 | Open Access

Discovery and preclinical evaluation of anti-miR-17 oligonucleotide RGLS4326 for the treatment of polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is a leading genetic cause of end-stage renal disease with limited treatment options. Here the authors discover and characterize a microRNA inhibitor as a potential treatment for ADPKD.

• Edmund C. Lee
• , Tania Valencia

Article 02 May 2019 | Open Access

TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells

Polycystin-2 (PC2) is an ion channel commonly found mutated in autosomal dominant polycystic kidney disease. Here Arhatte et al. identify transmembrane protein 33 (TMEM33) as a regulator of PC2 function at the endoplasmic reticulum, and find that deletion of TMEM33 protects mice from acute kidney injury.

• Malika Arhatte
• , Gihan S. Gunaratne
•  &  Amanda Patel

Article 13 June 2018 | Open Access

Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels

Mutations in the cation channel PKD2 cause human autosomal dominant polycystic kidney disease but its channel function and gating mechanism are poorly understood. Here authors study PKD2 using electrophysiology and cryo-EM, which identifies hydrophobic gates and proposes a gating mechanism for PKD2.

• , Xiaoyong Yang
•  &  Xing-Zhen Chen

Article 26 February 2018 | Open Access

Lkb1 deficiency confers glutamine dependency in polycystic kidney disease

Polycystic kidney disease (PKD) is characterized by the formation of large fluid-filled cysts. Here Flowers and colleagues show that loss of Lkb1, downregulated in PKD, renders kidney cells dependent on glutamine for growth, and suggest that inhibition of glutamine metabolism may prevent cyst development in PKD.

• Ebony M. Flowers
• , Jessica Sudderth
•  &  Thomas J. Carroll

Article 16 February 2017 | Open Access

microRNA-17 family promotes polycystic kidney disease progression through modulation of mitochondrial metabolism

Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening genetic disease that leads to renal failure. Here Hajarnis et al . show that miR-17 modulates cyst progression in ADPKD through metabolic reprogramming of mitochondria and its inhibition slows cyst development and improves renal functions.

• Sachin Hajarnis
• , Ronak Lakhia

Article 02 March 2016 | Open Access

mTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complex

Polycystic kidney disease (PKD) is a ciliopathy resulting from defective localization of membrane proteins such as PC-1 to the primary cilium, resulting in renal cysts, and is associated with another cystic genetic disease called tuberous sclerosis complex (TSC). Here the authors use kidney-specific Tsc1 and Pkd1 mice to show that mTORC1 signalling inhibits PC-1 biogenesis as a potential mechanism of TSC/PKD contiguous gene syndrome.

• Monika Pema
• , Luca Drusian
•  &  Alessandra Boletta

Article | 24 October 2013

Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis

Loss-of-function mutations in PKD1 , the gene encoding the plasma membrane receptor Polycystin-1, lead to renal cyst formation in polycystic kidney disease. Here, Castelli et al . show that Polycystin-1 interacts with the Par3 polarity complex and has a role in the morphogenesis of kidney tubules during mouse development.

• Maddalena Castelli
• , Manila Boca

Article | 04 December 2012

Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex

Polycystic kidney disease family proteins form heteromeric complexes with transient receptor potential channel subunits of the TRPP subfamily. Yu and colleagues find that the polycystic kidney disease protein, PKD1L3, is an ion channel pore-forming subunit in the acid-sensing PKD1L3/TRPP3 complex.

• , Maximilian H. Ulbrich
•  &  Jian Yang

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• News Releases

JAMA review highlights advances in kidney cancer research and care

University of North Carolina Health Care

“The Nobel Prize in Medicine or Physiology in 2019 was awarded for the discovery of how mammalian cells sense oxygen,” said William Kim, MD, the Rush S. Dickson Distinguished Professor of Medicine at UNC School of Medicine and co-leader of the UNC Lineberger Cancer Genetics Research Program. “One of the key components of this oxygen sensing pathway is the von Hippel-Lindau tumor suppressor gene, which is mutated in approximately 90% of kidney cancers. This deep understanding of kidney cancer biology has led to several important therapeutic advances in recent years.”

Credit: UNC Lineberger Comprehensive Cancer Center

CHAPEL HILL, North Carolina — New insights into the biology of kidney cancer, including those informed by scientific discoveries that earned a Nobel Prize, have led to advances in treatment and increased survival rates, according to a review by UNC Lineberger Comprehensive Cancer Center’s William Kim, MD , and Tracy Rose, MD, MPH .

Their observations, drawn from a meta-analysis of 89 studies published between January 2013 and January 2024, were published in JAMA Aug. 28.

“The Nobel Prize in Medicine or Physiology in 2019 was awarded for the discovery of how mammalian cells sense oxygen,” said Kim, the Rush S. Dickson Distinguished Professor of Medicine at UNC School of Medicine and co-leader of the UNC Lineberger Cancer Genetics Research Program. “One of the key components of this oxygen sensing pathway is the von Hippel-Lindau tumor suppressor gene, which is mutated in approximately 90% of kidney cancers. This deep understanding of kidney cancer biology has led to several important therapeutic advances in recent years.”

Kim trained as a post-doc with William G. Kaelin, Jr., MD, who was jointly awarded the 2019 Nobel Prize for demonstrating how the von Hippel-Lindau gene influences cellular responses to changing oxygen levels.

The American Cancer Society estimates that more than 81,500 people will be diagnosed with kidney cancer in the United States this year, and the disease will cause 14,300 deaths. While the incidence of kidney cancer has been increasing by approximately 1.5% annually in recent years, deaths have decreased by about 2% each year from 2016 to 2020.

This decline in deaths is largely due to improved treatments and early detection. “The majority of kidney cancer cases are now detected incidentally, often before symptoms appear,” said Kim. He noted that the widespread use of abdominal imaging for unrelated issues has led to the incidental diagnosis of kidney cancer. “More cases are being identified in earlier stages when the cancer is typically more responsive to treatment.”

Cigarette smoking and being overweight are major risk factors for kidney cancer and are linked to nearly half of the cases in the United States. Other risk factors include high blood pressure, a family history of kidney cancer, workplace exposure to certain chemicals, and hereditary conditions, such as von Hippel-Lindau disease.

Current treatment approaches include surgery to remove part or all of the kidney, ablation using targeted heat or cold to destroy the tumor, or active surveillance with imaging technologies to monitor the tumor. For cancers that have metastasized, or spread beyond the kidney, newer treatment options include immune checkpoint inhibitors, tyrosine kinase inhibitors, or a combination of the two approaches.

“Advanced, metastatic kidney cancer is highly treatable with targeted therapy, immunotherapy or a combination of these newer therapies,” said Rose, associate professor of medicine at UNC School of Medicine. “Understanding the science underlying the disease has allowed for the rational development of therapies that have positively affected many patients the past two decades.”

10.1001/jama.2024.12848

Method of Research

Meta-analysis

Subject of Research

Not applicable

Article Title

Renal Cell Carcinoma: A Review

Article Publication Date

28-Aug-2024

COI Statement

Rose has received grant support from Merck, Bristol Meyers Squibb and Syndax. Kim has received consulting fees from Focal Medical, OncoRev, and Janssen and owns stock in AbbVie, Amgen, Apellis, Arvinas, BeiGene, Bristol Myers Squibb, Eli Lilly, ImmunityBio, Moderna, Zentalis, Focal Medical, Natera, Novo Nordisk, Revolution Medicines, Tango Therapeutics, and Viking Therapeutics.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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