For many years, doctors have relied on a blood marker called creatinine to estimate how well the kidneys filter waste produced by muscle activity. More recent medical guidelines also recommend measuring cystatin C, a small protein produced by all cells in the body, as another way to assess kidney function. Because these two markers are affected by different biological processes, using both together can offer a clearer picture of kidney health and future risk than either test alone.

Two Tests, One Concerning Gap

Researchers from NYU Langone Health found that large differences between creatinine and cystatin C results are common, particularly among people who are already ill. In a large international analysis, more than one third of hospitalized patients had cystatin C results that suggested kidney function was at least 30% worse than what their creatinine levels indicated. This gap, the researchers say, may point to underlying disease that would otherwise go unnoticed.

“Our findings highlight the importance of measuring both creatinine and cystatin C to gain a true understanding of how well the kidneys are working, particularly among older and sicker adults,” said study co-corresponding author Morgan Grams, MD, PhD. “Evaluating both biomarkers may identify far more people with poor kidney function, and earlier in the disease process, by covering the blind spots that go with either test.”

The study was published in the Journal of the American Medical Association and was presented at the American Society of Nephrology’s annual Kidney Week conference.

Why Kidney Testing Matters Beyond Diagnosis

Accurate kidney function measurements are critical not only for detecting disease, but also for determining safe medication doses. Kidney performance helps guide dosing for cancer treatments, antibiotics, and many commonly prescribed drugs, according to Grams, who is the Susan and Morris Mark Professor of Medicine at the NYU Grossman School of Medicine.

In a separate study released the same day, the same research group reported that chronic kidney disease now affects more people worldwide than ever before and has become the ninth leading cause of death globally. Grams notes that better tools for early detection could allow patients to begin treatment sooner and reduce the need for extreme measures such as dialysis or organ transplantation. She is also a professor in the Department of Population Health at NYU Grossman School of Medicine.

A Massive Global Analysis

For the current study, investigators reviewed medical records, blood test results, and demographic information from 860,966 adults representing six different nationalities. All participants had both creatinine and cystatin C measured on the same day and were followed for an average of 11 years. The analysis accounted for factors that can influence these markers but are not directly related to kidney function, including smoking, obesity, and a history of cancer.

Conducted through the international Chronic Kidney Disease Prognosis Consortium, the research is the largest investigation so far to examine how differences between these two tests relate to long-term health outcomes. The consortium was created to improve understanding of chronic kidney disease and to support consistent global definitions of the condition and its risks.

Higher Risks Linked to Larger Differences

The study found that people whose cystatin C results showed kidney filtration at least 30% lower than their creatinine results faced significantly higher risks of death, heart disease, and heart failure. They were also more likely to develop severe chronic kidney disease that required dialysis or an organ transplant. Similar patterns were observed in 11% of outpatients and individuals who appeared healthy at the time of testing.

Grams pointed out that cystatin C testing was first recommended in 2012 by the international organization Kidney Disease — Improving Global Outcomes. Despite that guidance, a 2019 survey showed that fewer than 10% of clinical laboratories in the United States performed the test in-house. Since then, the two largest laboratory companies, Quest Diagnostics and Labcorp, have begun offering it.

“These results underscore the need for physicians to take advantage of the fact that more hospitals and health care providers are starting to offer cystatin C testing,” said study co-corresponding author Josef Coresh, MD, PhD, director of NYU Langone’s Optimal Aging Institute. “Physicians might otherwise miss out on valuable information about their patients’ well-being and future medical concerns.”

Coresh, who is also the Terry and Mel Karmazin Professor of Population Health at NYU Grossman School of Medicine, noted that among hospitalized Americans included in the study, fewer than 1% had been tested for cystatin C.

Study Support and Contributors

The research was funded by National Institutes of Health grant R01DK100446 and by the National Kidney Foundation.

Michelle Estrella, MD, MHS, of the University of California, San Francisco, served as the study’s first author, while Kai-Uwe Eckardt, MD, of Charite-Universitatsmedizin Berlin in Germany, was the senior author. Along with Grams and Coresh, co-leaders of the Chronic Kidney Disease Prognosis Consortium, NYU Langone contributors included Shoshana Ballew, PhD; Yingying Sang, MS; and Aditya Surapaneni, PhD. Additional investigators came from institutions across the United States, Europe, Asia, and Australia, reflecting the global scope of the research effort.

In a recent study published in Microbiology Spectrum, Heil and researchers at North Carolina State University in Raleigh set out to explore how flour choice affects the microbes living in sourdough starters. Their analysis showed that yeasts from the genus Kazachstania were consistently the most common across all starters. In contrast, the bacterial communities varied depending on the type of flour used.

What This Means for Bakers and Flavor

The findings suggest that changing flour types could influence the microbial makeup of a starter. “And because the microbial composition affects different traits, by altering the flour you could potentially alter how your bread tastes,” said Heil, the study’s senior author. More broadly, she explained that the results show just how responsive the sourdough microbiome is to environmental conditions.

Earlier research has shown that sourdough microbes are shaped by multiple influences, including the flour itself, the surrounding air and surfaces, and even the hands of the baker. Starters can be made with wheat, rye, barley, teff, millet, or other grains, each supplying a distinct set of nutrients that microbes depend on to grow.

A Classroom Experiment Sparks the Study

The research began with an educational project led by Enrique Schwarzkopf, Ph.D., a postdoctoral researcher in Heil’s lab and an avid sourdough baker. He created a program at a local middle school to teach students about fermentation and evolution. Schwarzkopf, who maintains a sourdough starter named Seth, encouraged students to test different flour combinations and feeding schedules to see which starter would grow the fastest.

To analyze the starters, the researchers used metabarcoding, a genetic method that quickly identifies which microbes are present in a sample. Each starter began with one of three substrates: all-purpose flour, bread flour or whole wheat flour. At the start of the experiment, the flours showed similar bacterial profiles and contained a variety of yeasts.

Unexpected Yeast Dominance

After several weeks of repeated feeding, the microbial communities shifted. The starters all ended up dominated by the same yeast, while bacteria showed greater diversity. Heil said she originally expected to find Saccharomyces cerevisiae, also known as brewer’s yeast, which is commonly used in baking and is central to much of her lab’s research.

Instead, Kazachstania emerged as the leading yeast in every starter, regardless of flour type or feeding schedule. Genetic analysis also revealed differences among bacteria. Starters made with whole wheat flour contained higher levels of Companilactobacillus, while those made with bread flour had more Levilactobacillus.

Flour as an Ecological Driver

Heil, whose work focuses on how organisms adapt to new environments and compete at the genetic level, explained that each flour type offers unique nutritional conditions. Linking those differences to the environments microbes experience, she said, can help scientists better understand how diverse microbial communities form, compete, and persist.

The project was led by Nima Rahbar, the Ralph H. White Family Distinguished Professor and head of the Department of Civil, Environmental, and Architectural Engineering. His team created ESM using an enzyme that helps turn carbon dioxide into solid mineral particles. These particles are then bonded together and cured under gentle conditions. The process allows the material to be shaped into structural components within hours.

Conventional concrete must be produced at very high temperatures and can take weeks to fully cure. In contrast, ESM forms quickly and leaves a much smaller environmental footprint.

Cutting Emissions by Capturing Carbon

“Concrete is the most widely used construction material on the planet, and its production accounts for nearly 8% of global CO₂ emissions,” said Rahbar. “What our team has developed is a practical, scalable alternative that doesn’t just reduce emissions — it actually captures carbon. Producing a single cubic meter of ESM sequesters more than 6 kilograms of CO₂, compared to the 330 kilograms emitted by conventional concrete.”

Built for Real-World Use

ESM combines fast curing with adjustable strength and full recyclability. These qualities make it well suited for practical applications such as roof decks, wall panels, and modular building systems. The material can also be repaired, which may lower long-term construction costs and significantly reduce how much waste ends up in landfills.

“If even a fraction of global construction shifts toward carbon-negative materials like ESM, the impact could be enormous,” added Rahbar.

Broad Potential Across Industries

Beyond standard construction, the material could support affordable housing, climate-resilient infrastructure, and disaster recovery efforts. Lightweight components that can be produced quickly may help speed rebuilding after extreme events. Because ESM relies on low-energy manufacturing and renewable biological inputs, it also supports broader goals tied to carbon-neutral infrastructure and circular manufacturing systems.

The discovery, made by researchers at UVA Health and Mount Sinai, could help doctors spot high-risk patients earlier and open the door to new treatments aimed at preventing or slowing heart failure in people with kidney disease.

“Kidney and heart disease can develop silently, so they are often discovered only after damage has already been done,” said researcher Uta Erdbrügger, MD, an internal medicine physician-scientist with the University of Virginia School of Medicine’s Division of Nephrology. “Our findings can help to identify patients at risk for heart failure earlier, enabling earlier treatment and improved outcomes.”

Heart Failure Risk in Chronic Kidney Disease

Chronic kidney disease affects more than 1 in 7 Americans, or roughly 35 million people in the United States, according to the National Institutes of Health. The condition is especially common among people with other health issues. About 1 in 3 patients with diabetes and around 1 in 5 people with hypertension (high blood pressure) also have kidney disease.

Doctors have long known that chronic kidney disease and cardiovascular disease are closely connected, with more severe kidney damage linked to worse heart outcomes. However, understanding exactly why this happens has been difficult. Many patients share overlapping risk factors such as obesity and high blood pressure, making it hard to determine whether the kidneys themselves play a direct role in harming the heart.

A Kidney-Specific Cause Identified

Until now, researchers had not been able to identify a kidney-specific factor that directly damages the heart. The new study led by Erdbrügger and her colleagues points to a clear culprit. Diseased kidneys release tiny particles known as “circulating extracellular vesicles” into the bloodstream.

Extracellular vesicles are produced by nearly all cells and normally act as messengers, transporting proteins and other materials between cells. In people with chronic kidney disease, however, these vesicles carry small, non-coding RNA called miRNA that the researchers found to be toxic to heart tissue.

Lab and Patient Evidence

In laboratory mice, preventing these extracellular vesicles from circulating led to noticeable improvements in heart function and reduced signs of heart failure. The research team also analyzed blood plasma samples from people with chronic kidney disease and from healthy individuals. Harmful extracellular vesicles were found in patients with kidney disease but not in healthy volunteers.

“Doctors always wondered how organs such as the kidney and heart communicate with each other. We show that EVs from the kidney can travel to the heart and be toxic,” Erdbrügger said. “We are just at the beginning to understand this communication.”

Toward Earlier Detection and New Treatments

The findings suggest that a blood test could one day be developed to identify people with chronic kidney disease who face the highest risk of serious heart problems. Researchers may also be able to design therapies that block or neutralize these circulating extracellular vesicles, reducing their damaging effects on the heart.

“Our hope is to develop novel biomarkers and treatment options for our kidney patients at risk for heart disease,” Erdbrügger said. “Potentially our work will improve precision medicine for CKD and Heart failure patients, so that each patient gets the exact treatment they need.”

Advancing Extracellular Vesicle Research

To help move this field forward, Erdbrügger is organizing a hands-on workshop for UVA scientists focused specifically on extracellular vesicle research. The five-day workshop begins Feb. 7.

Finding answers to the most pressing medical mysteries and developing new treatments for complex diseases are key goals of UVA’s new Paul and Diane Manning Institute of Biotechnology. The institute is designed to speed the transition from laboratory discoveries to real-world therapies that can save lives.

Findings Published

The research findings were published in the scientific journal Circulation. The article is open access, meaning it is available to read for free.

The research team included Xisheng Li Nikhil Raisinghani, Alex Gallinat, Carlos G. Santos-Gallego, Shihong Zhang, Sabrina La Salvia, Seonghun Yoon, Hayrettin Yavuz, Anh Phan, Alan Shao, Michael Harding, David Sachs, Carol Levy, Navneet Dogra, Rupangi Vasavada, Nicole Dubois, Erdbrügger and Susmita Sahoo. The scientists reported no financial conflicts of interest.

The study was funded by the National Institute of Health through grants HL140469, HL124187, HL148786, R01DK125856, 1-INO-2025-1704-A-N, R21AG07848, and R01DK133598.

Most available treatments focus on easing symptoms, but their benefits often fade over time. Now, researchers at Case Western Reserve University have identified a specific biological pathway that contributes to the underlying damage caused by the disease.

A Harmful Protein Chain Reaction

The study, recently published in Molecular Neurodegeneration, explains how the buildup of toxic proteins inside brain cells leads to the death of neurons responsible for movement, a hallmark of Parkinson’s disease.

“We’ve uncovered a harmful interaction between proteins that damages the brain’s cellular powerhouses, called mitochondria,” said Xin Qi, the study’s senior author and Jeanette M. and Joseph S. Silber Professor of Brain Sciences at the Case Western Reserve School of Medicine. “More importantly, we’ve developed a targeted approach that can block this interaction and restore healthy brain cell function.”

After three years of investigation, the team discovered that alpha-synuclein, a protein known to accumulate in Parkinson’s disease, abnormally binds to an enzyme called ClpP. This enzyme normally helps maintain cellular health, but the interaction disrupts its function.

Damage to the Brain’s Energy Supply

When alpha-synuclein interferes with ClpP, mitochondria begin to fail. These structures act as the cell’s energy generators, and their impairment triggers widespread neurodegeneration and brain cell loss. Experiments across several research models also showed that this molecular interaction speeds up the progression of Parkinson’s disease.

To counter this process, the researchers developed a treatment known as CS2. The compound is designed to block the damaging protein interaction and help mitochondria recover their normal function. CS2 acts as a decoy, drawing alpha-synuclein away from ClpP and preventing it from harming the cell’s energy systems.

In multiple study models, including human brain tissue, patient-derived neurons and mice models, CS2 reduced brain inflammation and led to improvements in movement and cognitive performance.

Targeting the Disease, Not Just Symptoms

“This represents a fundamentally new approach to treating Parkinson’s disease,” said Di Hu, a research scientist in the School of Medicine’s Department of Physiology and Biophysics. “Instead of just treating the symptoms, we’re targeting one of the root causes of the disease itself.”

The breakthrough builds on Case Western Reserve’s strengths in mitochondrial biology and neurodegenerative disease research, along with its collaborative environment and advanced experimental models. These resources helped translate basic biological insights into a potential therapeutic strategy.

Next Steps Toward Clinical Use

Over the next five years, the team aims to move the discovery closer to human clinical trials. Planned efforts include refining the drug for use in people, expanding safety and effectiveness testing, identifying key molecular biomarkers tied to disease progression, and advancing toward patient-focused treatments.

“One day,” Qi said, “we hope to develop mitochondria-targeted therapies that will enable people to regain normal function and quality of life, transforming Parkinson’s from a crippling, progressive condition into a manageable or resolved one.”