Mismatch Between Two Common Kidney Function Tests Indicates Serious Health Problems

Creatinine has long been the standard for measuring kidney filtration, while cystatin C — a protein produced by all human cells — has been recommended as a complementary marker because it is influenced by different biological factors. Together, the two measurements can provide a clearer view of kidney health, especially in older or medically complex patients. Now, a global study suggests that when these two routinely used kidney function tests disagree, the mismatch itself may be a warning sign of future illness.

The new research, conducted by NYU Langone Health (New York, NY, USA) and centers worldwide, shows that people whose cystatin C-based estimate of kidney filtration is substantially lower than the value calculated from creatinine may face higher risks of kidney failure, cardiovascular disease, and death, even if one test alone appears normal. The researchers analyzed data from 860,966 adults of multiple nationalities who had both blood tests performed on the same day and were followed for an average of 11 years.

More than one-third of hospitalized participants had cystatin C-based readings that were at least 30% lower than their creatinine-based values. These individuals had a higher likelihood of death, heart disease, heart failure, and progression to severe chronic kidney disease requiring dialysis or transplantation.

A similar pattern appeared in 11% of outpatients and seemingly healthy volunteers. Because kidney function guides the safe dosing of antibiotics, cancer therapies, and other drugs, early detection of reduced filtration is crucial. However, cystatin C testing remains uncommon, with less than 10% of US clinical labs offering it just a few years ago.

“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. “Physicians might otherwise miss out on valuable information about their patients’ well-being and future medical concerns.”

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