Grant Furthers Study of Machine Learning to Predict Kidney Decline

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Generated: 10/27/2021
Grant Furthers Study of Machine Learning to Predict Kidney Decline

The National Kidney Foundation today announced U.S. Department of Health and Human Services (HHS) awards totaling $12,050,000 to fund the development of breakthrough research in kidney disease. Funded with support from the Eunice Kennedy Shriver National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Center for Advancing Translational Sciences (NCATS), the awards include one for new investigator research and others to build on existing NIH-funded research.

Since 2008, research supported by HHS and NIDDK has led to an improved understanding of how certain features in blood samples can help doctors predict with greater accuracy who in the general population may be at greater risk of developing kidney disease and who may benefit from earlier intervention to preserve kidney function.

Through funding from the NIAMS Career Development Program, the National Library of Medicine’s Big Data to Information for Patient Care and Health (BD2IC) program, the National Institute on Drug Abuse’s Clinical Trial Training Programs, and NIDDK, a total of 10 investigators were awarded with grants totaling $2,636,500. The grants will allow their respective teams to develop novel, innovative tools to help identify patients at risk of developing kidney disease and facilitate earlier diagnosis and treatment of patients that are at risk of experiencing kidney failure.

“I’m deeply grateful for the support received by the NIH, and I am proud to serve patients through research that leads to advances in treatment,” commented the NIAMS Career Development Program’s award recipient, Dr. Kala Duggirala. “The BD2IC project is truly innovative in that it uses large data warehouses to combine and mine patient information for purposes of developing novel predictive tools. Since kidney diseases are often complicated by comorbidities, it is our hope that the information gained through study might also provide more insights into how other diseases may progress in vulnerable patients.”

The NIAMS Career Development Program, which received funding from the BD2IC program, provides three-year seed research awards for new investigators. The program, which debuted in 2012, seeks to provide young investigators with the tools and resources to become future leaders in patient-oriented research.

“Research on chronic kidney diseases and their management should include studies that are relevant to patients' experience of these conditions, and in the case of the kidney disease research, that should involve patient-based research,” commented Dr. David Gifford, Deputy Director of the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). "The support provided by the NIH BD2IC program is essential for those who are dedicated to advancing patient-centered research and to improving understanding of chronic kidney disease by patients."

Two grants totaling $1,525,000 will support the development of new predictive tools in kidney disease. One project will investigate how different biomarkers in patients with diabetic kidney disease can predict which patients are more or less likely to require RRT. The others will focus on how a patient’s genes can help predict which patients are at increased risk of developing kidney diseases that affect an area of the kidney called the medulla.

“With our grant from NIAMS, we will study novel genetic-based biomarkers that will allow us to predict which patients will benefit from early RRT and which patients will not need it,” said Dr. Jennifer Taylor, who will lead the project at the University of Wisconsin Carbone Cancer Center. “The National Kidney Foundation, the NIH, and all of the sponsors for this award are truly supporting groundbreaking research in kidney disease.”

Two projects totaling $1,315,000 were awarded to enable scientists to further their work on discovering and developing new drugs to slow the progression and progression of kidney failure over the long-term. The first team will test new drugs to reduce the immune system’s response to the harmful proteins (proteins called immune complexes) that may deposit in the kidney in some patients with the most common form of kidney failure known as focal segmental glomerulonephritis.

The second NIH-funded team will test the effectiveness of potential new drugs to treat patients with a rare kidney disease called Alport syndrome, which is often complicated by kidney failure and which has limited treatment options.

The NIAMS grant will support an investigator who will examine which drugs or biologics are the most effective in preventing chronic kidney disease in the majority of patients who get the disease, which is a leading cause of morbidity and mortality in the U.S.

“NIAMS has given us the support and encouragement we need to explore the most important long-term questions surrounding chronic kidney disease -- how will it affect the health and well-being of our kidneys?” explained Dr. William Wahlsten. “By enabling us to study whether and how existing drugs would prevent kidney failure, the NIAMS grant provides great potential for positive impact.”

Several scientists at the Mayo Foundation will also receive support. Two of these projects will test new drugs and are led by Drs. Timothy St Clair and Michael Wechsler. Dr. St Clair’s project will examine new drugs that target one of two protein complexes (called the MHC II receptor and the MHC receptor), called the Toll-like receptor TLR 9, that can be present within the body’s cells and trigger the immune system to attack tissue. The first project conducted in mice will seek to identify the safest and most effective drugs to trigger the immune system’s response in ways that do not lead to severe inflammation. Dr. Wechsler's team will attempt to identify additional drugs that will prevent the formation of immune complexes that deposit in the kidneys, in a discovery approach similar to one that has already been successful in the treatment of pulmonary artery hypertension. The other four teams, including Dr. St Clair, were awarded with individual research grants from the Mayo Clinic Developmental Center.

Also awarded funding was NCATS, which received two projects totaling $900,000.

“Our grant from the National Institute of Allergy and Infectious Diseases supports investigations to use new techniques to better understand how HIV-1 affects the immune system and develop novel therapies to boost a person’s immune response to HIV,” said Dr. Eric Pinter, who will lead one of the two projects. “Through this program, we may be able to achieve long-lasting control of HIV-1.”

The other project, led by Dr. Michael Mocroft, will seek to define the most effective ways to use a new class of drugs called monoclonal antibodies in patients who are infected with HIV.

“There are very exciting new approaches to treating HIV that have come of the scientific advances from the National Institutes of Allergy and Infectious Diseases,” noted Dr. Mocroft. “NIAMS has shown strong support for these projects, making them excellent fits for our new grant.”

Other awards for new investigator research include:

Dr. Joseph Kottler, National Institute of Allergy and Infectious Disease: To study the immune system’s response to drugs that are similar to those used to suppress the immune system in HIV.

Dr. Matthew O’Neal, National Institutes of Health Clinical Center: To develop new models of blood donation so doctors can learn more about blood.

Dr. Jennifer Cepko, National Institutes of Health Clinical Center: To identify drugs that prevent or slow the progression of type 2 diabetes.

Dr. Nisha A. Raj, University of Iowa: To understand how drugs work to stop HIV viral proteins to prevent the patient’s immune system from being damaged by the virus.

Dr. T. Ryan Williams, University of Iowa: To develop new methods to use human stem cells to prevent or slow type 1 diabetes.

The first-ever NIDDK awards will support research that seeks to develop improved understanding of kidney diseases. One NIDDK-funded research project will seek to determine how to better select patients with focal segmental glomerular sclerosis, one of the two underlying causes of nephrotic syndrome, a condition characterized by protein (mostly albumin) loss in the urine. Other NIH grants also focus on patients with nephrotic syndrome.

“Our understanding of how some patients experience glomerulonephritis is evolving rapidly,” explained Dr. James Gernsheimer, the study leader for the NIDDK project. "We will use what we learn from these patients to further develop methods to help identify those most at risk for chronic kidney disease and to determine which patients benefit from early intervention with RRT to reverse their kidney disease.”

A large-scale study conducted by scientists at University of California, San Diego will seek to develop more precise methods of measuring blood-based markers for two inflammatory disorders of the kidney, FSGS and lupus nephritis. The study, known as the Research to Improve Clinical Care for Patients with Nephrotic Syndrome to Ease Their End-of-Life Decision, will investigate and validate new or better ways to measure biomarkers of kidney inflammation for patients with these diseases.

The final NIH grant is for a study that will seek to identify and use a person’s gene expression, which is all the protein-making instructions carried on a person’s cells, to predict which drugs may best treat that individual.

"NIH’s support will help us explore the complex and challenging area of predicting how drugs can work in different patients, and how individual patients can be better treated,” explained Dr. Daniel R. Waggoner, the study leader.

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