Every day, your kidneys quietly filter toxins from your blood, balancing fluids and maintaining the body’s delicate chemistry. Most of us rarely think about these organs—until something goes wrong. For decades, doctors have relied on a simple blood test measuring creatinine, a molecule produced by muscle metabolism, to check how well the kidneys are working. But a new global study reveals that this familiar test may not always tell the full story.
Researchers at NYU Langone Health have found that when two common kidney tests—one measuring creatinine and the other measuring a different molecule called cystatin C—don’t agree, it could signal far more than a laboratory discrepancy. In fact, that mismatch might be a hidden alarm for future kidney failure, heart disease, and even early death.
The study, published in JAMA and presented at the American Society of Nephrology’s annual Kidney Week conference, highlights a discovery that could reshape how doctors evaluate one of the body’s most essential functions.
Rethinking How We Measure Kidney Health
For generations, the creatinine test has been the gold standard for estimating the kidneys’ ability to filter waste—a measure known as the glomerular filtration rate, or GFR. But creatinine has a limitation: it is influenced not only by kidney function but also by muscle mass, diet, and certain medications. A bodybuilder, for example, might have naturally higher creatinine levels that make their kidneys appear worse than they are. An older or frailer person, on the other hand, might seem to have healthy kidneys even when organ function is declining.
That’s where cystatin C comes in. Unlike creatinine, cystatin C is produced by nearly all cells in the body, making it a more consistent indicator of how well the kidneys are filtering blood. It is also less affected by factors such as age, muscle mass, or gender.
When used together, the two markers—creatinine and cystatin C—offer a clearer and more reliable picture of kidney health. But the NYU Langone team discovered that in many people, especially those who are sick or hospitalized, the two tests don’t match up. And that difference may be far more meaningful than anyone realized.
When the Numbers Don’t Agree
In the new study, researchers analyzed medical records and blood samples from nearly 861,000 people across multiple countries. Each participant had both creatinine and cystatin C levels measured on the same day, with follow-up data collected an average of 11 years later.
What they found was striking: more than one-third of hospitalized patients had a cystatin C-based estimate of kidney function that was at least 30% lower than the one based on creatinine. In other words, while one test suggested their kidneys were functioning fairly well, the other told a more alarming story.
This gap was not a trivial statistical blip. Those whose cystatin C results were significantly worse faced a much higher risk of severe chronic kidney disease, heart failure, cardiovascular events, and death. Even among outpatients and seemingly healthy individuals, about 11% showed this mismatch, and they too had elevated long-term health risks.
“Our findings highlight the importance of measuring both creatinine and cystatin C to gain a true understanding of how well the kidneys are working,” said Dr. Morgan Grams, co-corresponding author of the study and the Susan and Morris Mark Professor of Medicine at NYU Grossman School of Medicine. “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.”
Why a Mismatch Matters
At first glance, a disagreement between two lab values may not seem important. But this mismatch could reflect deeper biological realities. Creatinine levels might stay deceptively stable in a patient whose muscle mass is declining, while cystatin C could reveal the early stages of kidney deterioration.
Cystatin C has also been linked to other processes in the body, including inflammation and aging. When its levels rise disproportionately, it may indicate more widespread health concerns, not just kidney trouble. In essence, a cystatin C “red flag” could be an early sign that the body is under stress long before symptoms appear.
The researchers emphasize that this insight isn’t only about detecting disease—it’s also about saving lives. Accurate kidney assessment is critical for dosing many common medications, including antibiotics, diabetes treatments, and chemotherapy drugs. If kidney function is overestimated based on creatinine alone, patients might receive doses that their bodies can’t safely handle.
A Global Wake-Up Call
The findings arrive at a time when chronic kidney disease (CKD) is reaching alarming levels worldwide. In a related study published the same day, the same research team reported that CKD has become the ninth leading cause of death globally, affecting hundreds of millions of people.
What makes CKD especially dangerous is its stealth. It progresses quietly, often without symptoms until the kidneys are severely damaged. By then, patients may require dialysis or transplantation—treatments that are costly, invasive, and life-altering.
This is why early detection is so critical. The mismatch between cystatin C and creatinine readings may be one of the best early-warning systems medicine has ever had. It provides a chance to intervene before kidney function reaches the point of no return.
Why Isn’t Cystatin C Testing Common Yet?
Despite being first recommended by the international group Kidney Disease: Improving Global Outcomes (KDIGO) in 2012, cystatin C testing remains uncommon. A 2019 survey found that fewer than 10% of clinical laboratories in the United States performed it regularly.
This is slowly changing. The two largest U.S. diagnostic companies—Quest Diagnostics and Labcorp—now offer cystatin C testing, and more hospitals are beginning to adopt it. But according to co-author Dr. Josef Coresh, director of NYU Langone’s Optimal Aging Institute, usage is still far too low.
“Among hospitalized Americans in our study, less than 1% were tested for cystatin C,” Coresh noted. “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. Otherwise, they might miss valuable information about their patients’ well-being and future medical concerns.”
Looking Ahead: Toward Better, Earlier Detection
The message from this massive study is clear: one test alone is not enough. By combining creatinine and cystatin C, doctors can detect kidney problems earlier, understand disease risk more precisely, and tailor treatments more safely.
But the implications reach beyond nephrology. Because kidney function is so closely tied to overall health, improving its measurement could reshape preventive medicine more broadly. Early identification of kidney dysfunction may also uncover risks for heart disease, metabolic disorders, and premature aging—all interconnected through the body’s complex systems.
The NYU Langone team hopes their findings will push healthcare systems worldwide to make cystatin C testing standard practice, especially for older adults, hospitalized patients, and those with chronic illnesses. The cost of the test is small compared to the potential lives it could save.
The Kidneys’ Quiet Warning
Your kidneys are quiet organs, working tirelessly behind the scenes to keep your blood clean and your body in balance. When they begin to fail, the early signs are often too subtle to notice—until the damage is done. But science is now learning to listen more closely to their whispers.
By reading the hidden messages in our blood—through both creatinine and cystatin C—doctors may finally be able to catch kidney disease before it becomes irreversible. The hope is that one day, a simple double-check on a lab report will mean the difference between years of silent decline and a lifetime of health.
In the end, this research is not just about numbers or lab values—it’s about listening more carefully to the quiet signals our bodies send us. Sometimes, the smallest mismatch can reveal the biggest truth.
More information: Discordance In Creatinine-and Cystatin-C-Based eGRF and Clinical Outcomes, JAMA (2025). DOI: 10.1001/jama.2025.17578
