French researchers have developed and validated a creatinine-based, race-free equation for calculating estimated glomerular filtration rate (eGFR) in people who have received a kidney transplant. It performed as well, or better, than three established eGFR equations, including the 2021 race-free equation now widely used in US practice.
“The new equation provides a more accurate estimation of kidney function” in kidney transplant recipients compared with prior equations, said Marc Raynaud, PhD, lead author of the report, which was recently published in BMJ.
In transplant recipients, most clinical decision-making is partly based on eGFR, he noted. “Since eGFR will be more accurate with our equation, routine clinical decision-making will be more informed and made more precisely,” said Raynaud, a researcher at the French Institute of Health and Medical Research (INSERM) in Paris, France.
Close to Routine Use
“We’ll soon use this equation in our kidney transplant program,” added Raynaud in an interview. He also foresees “widespread uptake” of the new eGFR equation “in the near future. Ultimately, the new equation will become standard for kidney recipients,” he predicted.
Raynaud and colleagues posted an eGFR calculator based on their new equation using sex, age, and serum creatinine as the input variables.
Kidney transplant recipients are a “complex, distinct population in terms of comorbidities and determinants of kidney failure and death. Overall, this multidimensional complexity justified the need to develop an equation to estimate GFR in kidney transplant recipients,” the authors write.
“Kidney recipients do not share the exact same characteristics as patients with chronic kidney disease who are not transplanted. The current kidney function equations, developed in native kidneys, may not therefore be adapted to kidney recipients, which limits adequate kidney-recipient monitoring,” said Alexandre Loupy, MD, PhD, professor of nephrology at Necker Hospital in Paris, and senior author of the new report, in a written statement.
“Marginally but Not Substantially Better”
Based on the data in the report, performance characteristics of the new equation “are marginally but not substantially better” than existing options for patients with a kidney transplant, commented Neil R. Powe, MD, chief of medicine at Zuckerberg San Francisco General Hospital, California, who co-developed the 2021 race-free eGFR equations based on creatinine alone, cystatin C alone, and both.
The new equation for kidney transplant patients “adds another equation to the mix for clinicians to use in kidney transplant recipients,” Powe said in an interview.
The researchers used “standard methods for developing the equation,” he noted.
But Powe added that he would like to see evidence for the performance of the new equation in “a more diverse group,” and said the fact it is not based on both creatinine and cystatin C is “a limitation” of the new equation.
Serum levels of cystatin C are considered to more reliably and consistently reflect kidney function compared with serum creatinine but testing for cystatin C remains much less available and used compared with creatinine.
Raynaud explained that data on cystatin C levels had not been available because this marker is “virtually never assessed in transplant centers worldwide.”
“Applicable Anywhere in the World“
For the development phase, the French researchers used data from 3622 kidney transplant patients at three French hospitals in 2000-2021.
To validate the equation, they used data from nearly 11,000 kidney transplant patients seen at any one of 11 centers located in seven countries including the United States, Australia, and four European countries in addition to France. Validation also included data from more than 1100 patients enrolled in any of three trials, creating a total development and validation cohort of more than 15,000 patients and more than 50,000 GFR measurements. The median time from transplantation to GFR measurement was just over 2 years.
“We made sure that the equation was applicable to any transplanted population in the world,” said Raynaud.
Performance assessments showed that compared with measured GFR, results from the new race-free, kidney-recipient–specific eGFR equation were similar to those of the Modification of Diet in Renal Disease equation, available since 1999 and uses a correction factor for race.
The new equation showed significantly superior performance to the next-generation CKD-EPI equation that came out in 2009 and also uses a correction factor for race. The researchers also conclude that the new equation “showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys.”
The study received no commercial funding. Raynaud and Powe have reported no relevant financial relationships. Loupy is a stockholder in Cibiltech.
BMJ. 2023;381:e073654. Full text
Mitchel L. Zoler is a reporter for Medscape and MDedge based in the Philadelphia area. @mitchelzoler
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