Mismatch Between Two Kidney Function Tests Signals Future Disease

Amismatch between two common tests for kidney function may indicate a higher risk for kidney failure, heart disease, and death, a new study shows.

Healthcare providers for decades have measured blood levels of the molecule creatinine to track the rate at which kidneys filter waste from muscle breakdown in the bloodstream. According to more recent guidelines, levels of cystatin C, a small protein made by all cells in the body, can also be used to measure kidney function. Since these two tests are influenced by different factors—including some related to disease or aging—using both markers together can provide a better measure of kidney function and risk of organ failure than either one alone.

Led by NYU Langone Health researchers, the new work reveals that many people, especially those who are sick, often have a large gap between the two readings, which may be a signal of future disease. Specifically, the global study shows that more than a third of hospitalized participants had a cystatin C-based readout of kidney function that was at least 30 percent lower than one based on their creatinine levels.

“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 published online November 7 in the Journal of the American Medical Association and is simultaneously being presented at the American Society of Nephrology’s annual Kidney Week conference.

Beyond detecting signs of disease, assessing patients’ kidney function is important for calculating the appropriate dosage for cancer medicines, antibiotics, and many other drugs, says Dr. Grams, the Susan and Morris Mark Professor of Medicine at the NYU Grossman School of Medicine.

During another investigation, the results of which were published the same day, the same research team found that a record number of people worldwide have chronic kidney disease, which is now the ninth leading cause of death globally. Having new ways to spot the condition early can help ensure that patients receive swift treatment and avoid more-dramatic interventions such as dialysis and organ transplantation, says Dr. Grams, who is also a professor in the Department of Population Health at NYU Grossman School of Medicine.

For the recent investigation, the research team analyzed healthcare records, blood tests, and demographic data collected from 860,966 men and women of a half-dozen nationalities. All participants had their creatinine and cystatin C levels measured on the same day and received follow-ups 11 years later, on average. The team considered factors unrelated to kidney function that influence the biomarkers’ readings, such as smoking, obesity, and history of cancer.

Performed as part of the international Chronic Kidney Disease Prognosis Consortium, the study is the largest to date to explore differences between the two tests and whether they may signal potential health problems, the authors say. Established to better understand and treat the condition, the consortium provides evidence for global definitions of chronic kidney disease and related health risks.

According to the new findings, those whose cystatin C-based measures of kidney filtration were at least 30 percent lower than their creatinine-based measures were at higher risk for death, heart disease, and heart failure than those who had a smaller difference between the two metrics. The former group was also more likely to be diagnosed with severe chronic kidney disease that required dialysis or an organ transplant. The same was found for 11 percent of outpatients and seemingly healthy volunteers.

Dr. Grams notes that while cystatin C testing was first recommended in 2012 by the international organization Kidney Disease—Improving Global Outcomes, a 2019 survey revealed that less than 10 percent of clinical laboratories in the United States performed it in-house. The two largest laboratories, Quest Diagnostics and Labcorp, now offer the test.

“These results underscore the need for physicians to take advantage of the fact that more hospitals and healthcare 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’ wellbeing and future medical concerns.”

Dr. Coresh, who is also the Terry and Mel Karmazin Professor of Population Health at NYU Grossman School of Medicine, cautions that among the hospitalized Americans in the study, less than 1 percent were tested for cystatin C.

Reference: Estrella MM, Ballew SH, Sang Y, et al. Discordance in creatinine- and cystatin c–based eGFR and clinical outcomes: A meta-analysis. JAMA. 2025. doi: 10.1001/jama.2025.17578

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.