Bold truth: When kidney tests don’t agree, your health risks become clear—and this matters for millions. Here’s how two standard blood tests can alter how we view kidney health, and why combining them could save lives.
Chronic kidney disease (CKD) affects over 35 million people in the United States alone. The kidneys filter toxins, electrolytes, and excess water from the blood, helping keep the body in balance. When kidney function declines, the risk of kidney failure, cardiovascular disease, and other serious health problems rises. Doctors commonly estimate kidney function with the estimated glomerular filtration rate (eGFR). A higher eGFR signals better kidney filtration.
Two different blood tests can estimate eGFR: one measures a metabolic byproduct called creatinine, and the other measures a small protein called cystatin C. Each test has its own potential confounders beyond kidney function—diet, muscle mass, age, inflammation, and more—so it’s possible for the two tests to yield notably different eGFR values for the same person. In fact, prior research has flagged that a difference of about 30% between the tests can be clinically meaningful.
A recent study led by Drs. Morgan Grams and Josef Coresh from the NYU Grossman School of Medicine delved into how often these creatinine- and cystatin C-based eGFR values diverge. They analyzed data from an NIH-supported global initiative tracking kidney function and damage since 2009. The study, published November 7, 2025 in JAMA, combined results from more than 800,000 outpatient patients who had both tests and nearly 40,000 hospitalized patients who did as well. Patients were followed for an average of 11 years after their eGFR measurements.
Key findings show a striking divergence: about 11% of outpatients and 35% of hospitalized patients had cystatin C-based eGFR values at least 30% lower than their creatinine-based eGFR. For outpatients, a larger discrepancy correlated with higher all-cause mortality over the follow-up period, and with greater risks of cardiovascular disease, heart failure, and kidney failure. In other words, the bigger the gap between the two eGFR estimates, the greater the health risk observed.
Conversely, outpatients whose cystatin C-based eGFR was at least 30% higher than their creatinine-based eGFR tended to have lower risk for several adverse outcomes compared with those with smaller differences. This contrast highlights that the direction and magnitude of discordance between tests carry meaningful prognostic information.
What does this mean in practice? Measuring both creatinine and cystatin C to estimate eGFR can provide a more complete picture of kidney function, especially in older adults or those with other health burdens. Using both biomarkers may help identify people with CKD who are at higher risk for health complications earlier in the disease process, enabling closer monitoring and timely interventions. More research is needed to uncover why these tests diverge in some individuals and what underlying factors drive the differences.
“As our findings show, relying on a single biomarker can obscure the true state of kidney function,” says Grams. “Evaluating both creatinine and cystatin C offers a clearer view of kidney health, potentially revealing risk earlier and guiding preventative care.”
— by Brandon Levy
Related links and references are provided to offer context and further reading on kidney health, disease prevention, and the CKD Prognosis Consortium’s work.
