NIH-funded Study Finds More Precise Way to Estimate Kidney Function

Measuring creatinine and cystatin C—two markers for chronic kidney disease (CKD)—more precisely estimates kidney function than either marker alone, according to a study funded by the National Institutes of Health. Results appear in the July 5 issue of the New England Journal of Medicine.

“Glomerular filtration rate, or GFR, estimates based on creatinine in the blood are routinely used to measure kidney function and diagnose chronic kidney disease. However, estimating GFR using creatinine alone is imprecise and may lead to over-diagnosis in some patients,” said Dr. Lesley Inker, a nephrologist at Tufts Medical Center in Boston and lead study author.

According to Dr. John Kusek, study co-author and senior scientific advisor, Division of Kidney, Urologic, and Hematologic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of NIH, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study illustrates the importance of research to more accurately estimate kidney function in order to improve the certainty of CKD diagnosis. “The findings in this most recent work represent an important step in that direction,” he said.

Creatinine is a waste product from protein in the diet and the normal breakdown of muscle tissue. Cystatin C is released by cells throughout the body. The kidneys remove both creatinine and cystatin from the blood. As kidney function worsens, the creatinine and cystatin levels in the blood increase.

“The new creatinine-cystatin equation is more accurate over a broader range of kidney function and body size, and less altered by other medical conditions,” said Inker. “Estimating kidney function based on creatinine and cystatin C could be used as a confirmatory test for chronic kidney disease in patients with an estimated GFR near 60—the usual threshold for diagnosing chronic kidney disease—although it will need to be standardized before the equation can be used widely.”

Testing kidney function is often part of routine medical care for adults, according to Inker. More than 80 percent of clinical laboratories currently estimate GFR from serum creatinine. Despite efforts to standardize serum creatinine measurement across all labs, GFR estimates remain relatively imprecise due to variation in creatinine levels that are not related to GFR, such as those affected by differences in muscle mass, malnutrition, and other chronic illnesses. This imprecision can potentially misclassify patients as having CKD when they may not, or conversely, miss the diagnosis in patients who do have CKD. Over-diagnosis can lead to unnecessary treatment such as medication and dietary changes.

The CKD-EPI study estimated kidney function based on creatinine alone and with cystatin C, developed in a diverse group of 5,352 people from 13 studies that measured kidney function.

The creatinine-cystatin C equation performed better than equations using only creatinine or cystatin C. In people whose estimated kidney function was between 45 and 74 based on creatinine, the combined equation improved classification for measured GFR below 60, correctly reclassifying 16.8 percent of those with estimated GFR of 45 to 59 to 60 or greater.

Based on projections from the National Health and Nutrition Examination Survey, using the creatinine-only equation, an estimated 23 million American adults may have CKD, and nearly 400,000 people in the United States and 2 million worldwide depend on dialysis to treat kidney failure.