A new study led by NYU Langone Health researchers has found that a significant mismatch between two commonly used tests for kidney function may signal an increased risk of kidney failure, heart disease, and death. Traditionally, healthcare providers have measured blood creatinine levels to assess how well the kidneys filter waste from muscle breakdown. More recent guidelines recommend also using cystatin C, a protein produced by all cells in the body, as another indicator of kidney function.
The study reveals that these two tests are affected by different factors such as disease or aging. Using both markers together can provide a more accurate assessment of kidney health than relying on just one. Researchers discovered that many people—especially those who are ill—have large differences between their creatinine and cystatin C test results. In particular, over one-third of hospitalized participants had cystatin C-based measurements that were at least 30 percent lower than those 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.”
The research was published online November 7 in the Journal of the American Medical Association and presented at the American Society of Nephrology’s annual Kidney Week conference.
Dr. Grams noted that beyond identifying disease risks, assessing kidney function is important for determining correct dosages for medications like cancer drugs and antibiotics.
Another related investigation published on the same day showed chronic kidney disease is now the ninth leading cause of death globally. Early detection could help patients receive timely treatment and potentially avoid interventions such as dialysis or transplantation.
For this recent study, data from nearly 861,000 individuals across several countries were analyzed. All participants had their creatinine and cystatin C levels measured on the same day with follow-ups averaging 11 years later. The analysis took into account unrelated factors influencing test results such as smoking history, obesity, and cancer.
Conducted under the international Chronic Kidney Disease Prognosis Consortium—which works to define chronic kidney disease globally—the study is described as the largest to date exploring discrepancies between these two tests.
Findings indicate that those whose cystatin C-based readings were at least 30 percent lower than their creatinine-based ones faced higher risks for death, heart disease, heart failure, severe chronic kidney disease requiring dialysis or transplant. This pattern was also seen in outpatients and healthy volunteers.
While cystatin C testing has been recommended since 2012 by Kidney Disease—Improving Global Outcomes (KDIGO), only a small percentage of U.S. clinical laboratories performed it in-house as recently as 2019. However, major labs such as Quest Diagnostics and Labcorp now offer this 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 added that among hospitalized Americans included in this research less than 1 percent received cystatin C testing.
Funding support came from National Institutes of Health grant R01DK100446 and by the National Kidney Foundation.
Michelle Estrella at University of California San Francisco was first author; Kai-Uwe Eckardt at Charite-Universitatsmedizin Berlin served as last author; other co-leaders included Drs. Grams and Coresh along with additional NYU Langone researchers Shoshana H. Ballew; Yingying Sang; Aditya Surapaneni; Teresa Chen; Michael Shlipak; Natalia Alencar de Pinho; Johan Arnlov; Hermann Brenner; Juan-Jesus Carrero; Debbie Cohen; Mary Cushman; Ron Gansevoort; Shih-Jen Hwang; Lesley Inker; Andrew Levey; Joachim Ix; Keiko Kabasawa; Tsuneo Konta; Jennifer Lees; Kevan Polkinghorne; Robin Vernooij; David Wheeler; Ashok Kumar Yadav.
NYU Langone Health operates an integrated health system known for high patient outcomes according to Vizient rankings (https://newsroom.nyulangone.org/news/nyu-langone-health-named-no-1-comprehensive-academic-medical-center-fourth-consecutive-year) and offers services through multiple inpatient locations—including Perlmutter Cancer Center—and more than 320 outpatient sites in New York and Florida (https://nyulangone.org/locations). It includes tuition-free medical schools in Manhattan and Long Island alongside its research programs (https://med.nyu.edu/research).
