When there is a wide discrepancy between results of a newer blood test for evaluating kidney function and the results of an older test, the new diagnostic accurately identifies high-risk patients, researchers found.
The new test measures a protein called cystatin C. The older and still standard method for assessing the health of the kidney's tiny blood filters, or glomeruli, involves blood tests for a waste product from muscle breakdown called creatinine.
However, creatinine levels depend in part on muscle mass, creating variability across age, sex, nutritional status, and medication use. Until recently, racially biased misconceptions about muscle mass led doctors to also consider skin color in interpreting kidney health based on creatinine levels.
New guidelines recommend consideration of cystatin C for estimating the glomerular filtration rate (GFR). Unlike creatinine, plasma levels of cystatin C are not affected by muscle mass, although they are affected by certain medical conditions.
In a new study of more than 800,000 patients in whom GFR was estimated using both cystatin C and creatinine, researchers saw wide discrepancies in some participants.
Overall, in 11% of outpatients, estimated GFR was significantly worse - at least 30% lower, indicating more advanced kidney disease – based on cystatin C measurement, researchers reported at the American Society of Nephrology Kidney Week 2025 meeting in Houston and in JAMA.
During follow-up for an average of 11 years, these patients had significantly higher rates of death, cardiovascular events, and need for dialysis or kidney transplant compared with patients without such significant discrepancies between cystatin- and creatinine-based estimates of renal function.
Similar discrepancies were also seen in 35% of hospitalized patients, but the implications in this group were not as clear as in the outpatients and more research is needed, the authors said.
"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," study leader Dr. Morgan Grams of NYU Langone Health said in a statement.
"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," Grams said.
Healthcare systems that have successfully implemented in-house cystatin C testing have seen improved clinical decision-making, experts not involved in the study wrote in a JAMA editorial.
"Given its higher cost, cystatin C cannot fully replace creatinine measurement," the editorial noted.
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