Being continuous between ages 2 to 100 years, the European Kidney Function Consortium (EKFC) equation also avoids the unlikely jumps in GFR seen when transitioning from the Chronic Kidney Disease in Children Study (CKiD) equation for children to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults, researchers report in Annals of Internal Medicine.
"The main clinical implication is that when a subject has a normal serum creatinine for his/her age and sex (for adults this is a stable serum creatinine), he/she will have a stable and normal estimated GFR," said lead author Dr. Hans Pottel of KU Leuven, in Belgium. "As serum creatinine (Scr) is the biomarker for kidney function, this might seem quite obvious; however, the currently recommended equations don't show that behavior."
"In children, the CKiD equation overestimates GFR at very young age (for normal Scr) and underestimates GFR at the transition age of 18 year," he explained. "CKD-EPI overestimates GFR for young adults (18-40 years) at normal Scr-values (causing implausible jumps at the transition age of 18 years). Another important feature of our new equation is that it is an age-dependent equation, also for children, allowing to report eGFR along with Scr, also for children, which is not the case now (as CKiD is height-dependent, and height is a variable that is not available in the clinical laboratory). This makes mass screening for kidney malfunction in children much easier."
KDIGO, a global non-profit organization whose guidelines recommend the CKiD and CKD-EPI equations, did not respond to a request for comment.
But Dr. Andrew S. Levey of Tufts Medical Center, in Boston, who coauthored an editorial accompanying the new findings, cautioned the new equation might not apply to populations of mixed race/ethnicity.
"It may not be generalizable (it didn't work as well in our large database), and it did not include ethnic and racial minorities in its development dataset," he told Reuters Health by email.
The EKFC equation combines features of the full-age spectrum (FAS) and the CKD-EPI equations. To develop and test it, Dr. Pottel and his colleagues used data from more than 19,000 participants in 13 studies, all of which had been conducted in Europe or North America and included only white patients.
There was little bias across the FAS of 2 to 90 years, with a median difference between estimated (e) and measured (m) GFR of -1.2 mL/min/1.73 m2 in children and -0.9 mL/min/1.73 m2 in adults.
The EKFC equation also had higher accuracy than the currently recommended models, as assessed by the percentage of eGFR within 30% of mGFR (P30).
"The difference in P30 values in the external validation data set indicates that the EKFC equation has about 6.5 fewer estimation errors exceeding 30% per 100 children and 3.1 fewer per 100 adults than the CKiD and CKD-EPI equations, respectively," the researchers write.
Dr. Pottel said the "equation is ready for use, but limited to whites." The so-called Q-values - averaged sex- and age-specific serum creatinine values from healthy people used to normalize results - have yet to be defined for Blacks or other ethnicities, he added.
"This is work in progress," Dr. Pottel said. "We will evaluate the possibility to use our equation for other ethnicities, by defining appropriate Q-values. We will then prepare a web-based tool so that physicians can estimate GFR by simply filling in patient characteristics."
In their editorial, Dr. Levey and his colleagues say strengths of the new analysis "include a large study population with a wide range of ages and mGFRs, standardized assays for SCr and acceptable methods for mGFR, and rigorous statistical evaluation."
But when they compared the performance of the EKFC against that of the CKD-EPI equation in a dataset that included Blacks, their results did not match Dr. Pottel and his colleagues' findings: Among non-Black, mostly white people, the EKFC equation had a lower P30 than the CKD-EPI equation. And among Blacks, it had greater bias.
"We agree that a single eGFR equation that can be used in children and adults and performs well in the transition from adolescence to young adulthood is a worthy goal," they write. "We conclude that the EKFC equation and variations of the (Lund-Malmoe revised) and CKD-EPI equations represent a conceptual advance over the FAS equations, but the claim of equivalent or superior performance compared with the CKD-EPI equation is not conclusive."
By Frederik Joelving
SOURCE: https://bit.ly/3kclqap and https://bit.ly/3lhly9Q Annals of Internal Medicine, online November 10, 2020.
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