Disagreement between two kidney function tests predicts serious health problems

A difference between two common kidney function tests may indicate a higher risk of kidney failure, heart disease and death, a new study suggests.

For decades, health care providers have measured blood levels of the molecule creatinine to track how quickly the kidneys filter waste products from muscle breakdown into the bloodstream. According to newer guidelines, levels of cystatin C, a small protein made by all cells in the body, can also be used to measure kidney function. Because these two tests are influenced by different factors, including some related to disease or aging, using both markers together may provide a better measure of kidney function and organ failure risk than either alone.

Led by researchers at NYU Langone Health, the new work reveals that many people, especially those who are sick, often have a large discrepancy between the two readings, which can be a sign of future illness. Specifically, the global study shows that more than a third of hospitalized participants had a kidney function result based on cystatin C that was at least 30% lower than that based on their creatinine levels.

“Our findings highlight the importance of measuring both creatinine and cystatin C to better understand kidney function, particularly in older, sicker adults,” said study co-corresponding author Morgan Grams, MD, Ph.D. “Assessing both biomarkers could identify many more people with poor kidney function, and earlier in the disease process, covering blind spots associated with either test.”

The study will be published online on November 7 in the JAMA and is concurrently 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 of cancer drugs, antibiotics and many other medications, says Grams, the Susan and Morris Mark Professor of Medicine at the NYU Grossman School of Medicine.

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

For the recent survey, the research team analyzed health records, blood tests and demographic data collected from 860,966 men and women of half a dozen nationalities. All participants had their creatinine and cystatin C levels measured on the same day and were followed up 11 years later on average. The team took into account factors unrelated to kidney function that influence biomarker readings, such as smoking, obesity and history of cancer.

Carried out as part of the International Chronic Kidney Disease Prognosis Consortium, the study is the largest to date to explore the differences between the two tests and determine whether they can signal potential health problems, the authors say. Created to better understand and treat this disease, the consortium provides evidence on global definitions of chronic kidney disease and its associated health risks.

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

Grams notes that although the cystatin C test was first recommended in 2012 by the international organization Kidney Disease—Improving Global Outcomes, a 2019 survey found that fewer 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 findings highlight the need for physicians to take advantage of the fact that more hospitals and health care providers are beginning to offer cystatin C testing,” said study co-corresponding author Josef Coresh, MD, Ph.D., director of the Optimal Aging Institute at NYU Langone. “Otherwise, doctors could miss 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 the NYU Grossman School of Medicine, cautions that among the Americans hospitalized in the study, less than 1% were tested for cystatin C.