A Simple Blood Test Mismatch May Predict Kidney Failure, Heart Disease, and Death

Disagreement between creatinine and cystatin C kidney tests signals a much higher risk of serious disease and death, suggesting both measures should be used together.

A new study suggests that when two widely used tests of kidney function do not align, patients may face a greater risk of kidney failure, heart disease, and death.

For many years, clinicians have relied on blood levels of creatinine to estimate how effectively the kidneys remove waste produced by muscle metabolism. More recent medical guidelines also recommend measuring cystatin C, a small protein produced by all cells in the body, as another indicator of kidney function.

Because creatinine and cystatin C are affected by different biological factors, including illness and aging, evaluating both together can offer a more accurate picture of kidney health and the likelihood of organ failure than using either test on its own.

A gap that predicts future disease

Researchers from NYU Langone Health found that large differences between the two test results are common, particularly among people who are already unwell, and that these gaps may signal future health problems. In the international study, more than one-third of hospitalized participants showed cystatin C based estimates of kidney function that were at least 30 percent lower than estimates based on creatinine.

“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.”

Why accurate kidney assessment matters

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

Accurate measurement of kidney function is not only essential for detecting disease but also for determining safe and effective doses of medications, including cancer treatments, antibiotics, and many commonly prescribed drugs, said Grams, the Susan and Morris Mark Professor of Medicine at the NYU Grossman School of Medicine.

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

Global data reveal long-term risks

For the recent investigation, the research team analyzed health care 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% 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% of outpatients and seemingly healthy volunteers.

Closing the testing gap

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% 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 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, cautions that among the hospitalized Americans in the study, less than 1% were tested for cystatin C.

Reference: “Discordance in Creatinine- and Cystatin C–Based eGFR and Clinical Outcomes: A Meta-Analysis” by Michelle M. Estrella, Shoshana H. Ballew, Yingying Sang, Morgan E. Grams, Josef Coresh, Aditya Surapaneni, Natalia Alencar de Pinho, Johan Ärnlöv, Hermann Brenner, Juan-Jesus Carrero, Teresa K. Chen, Debbie L. Cohen, Mary Cushman, Ron T. Gansevoort, Shih-Jen Hwang, Lesley A. Inker, Joachim H. Ix, Keiko Kabasawa, Tsuneo Konta, Jennifer S. Lees, Kevan R. Polkinghorne, Michael G. Shlipak, Robin W. M. Vernooij, David C. Wheeler, Ashok Kumar Yadav, Andrew S. Levey, Kai-Uwe Eckardt, Chronic Kidney Disease Prognosis Consortium Investigators and Collaborators, Teresa K Chen, Yingying Sang, Morgan E Grams, Josef Coresh, Steven Chadban, Kevan Polkinghorne, Nisha Bansal, Joachim H Ix, Michael G Shlipak, Marie Metzger, Benedicte Stengel, Martin Landray, John N Townend, Jonathan Emberson, Chi-yuan Hsu, Wei Yang, Amanda Anderson, Hermann Brenner, Dietrich Rothenbacher, Ben Schöttker, Hannah Stocker, Daniel Levy, Martin Larson, Anna Kottgen, Peggy Sekula, Ulla T Schultheiss, Markus P Schneider, Vivek Kumar, Manisha Sahay, Narayan Prasad, Robin WM Vernooij, Andrew S Levey, Lesley A Inker, Mark Sarnak, Orlando M Gutierrez, Mary Cushman, Stephan JL Bakker, Lyanne M Kieneker, Marco van Londen, Katharine Cheung, Titi Ilori, Edouard L Fu, Anne-Laure Faucon, Aurora Caldinelli, Antoine Creon, Tsuneo Konta, Kazunobu Ichikawa, Satoru Nagase, Masafumi Watanabe, Jennifer S Lees, Patrick B Mark, Anders Larsson, Vilmantas Giedraitis, Keiko Kabasawa, Yumi Ito, Junta Tanaka, Ichiei Narita, Michelle Estrella, Shoshana H Ballew, Juan-Jesus Carrero, Ron T Gansevoort, Kunihiro Matsushita, Dorothea Nitsch, Angela Yee-Moon Wang, Carina M Flaherty and Aditya Surapaneni, 7 November 2025, JAMA.
DOI: 10.1001/jama.2025.17578

Meeting: ASN Kidney Week

Funding for the study was provided by National Institutes of Health grant R01DK100446 and by the National Kidney Foundation.

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