Flawed Racial Assumptions in eGFR Have Care Implications in CKD

In August, the American Society of Nephrology (ASN) and the National Kidney Foundation (NKF) created a joint task force to reevaluate the long-standing use of including race in a calculation to diagnose kidney disease. The inclusion of race can affect care decisions, according to proponents of making a change.

One of those advocates, Nwamaka D. Eneanya, MD, MPH, a nephrologist and assistant professor of medicine at the Hospital of the University of Pennsylvania, walked attendees at an ASN Kidney Week session this weekend through the history, hazards, and pitfalls of using estimated glomerular filtration rate (eGFR) equations, which use a multiplier to assign higher values to Black patients.

As higher values indicate better kidney function, there has been increasing recognition that this may lead to inequitable and delayed care.

Eneanya, one of the members of the task force, also discussed how she uses alternative diagnostic approaches with her patients, ones that meet the standards of transparency and shared decision making.

Her talk, part of a wider session on race and ethnicity in chronic kidney disease (CKD), comes as more institutions have moved to stop relying on the eGFR, such as the University of Washington, Beth Israel Deaconess Medical Center, and Mass General Brigham.

GFR is the total volume of filtrate passing through the glomeruli each minute, but that is challenging to assess in real-time in a physician’s office. Using serum creatine, factoring in age, height, weight, and gender, gives an estimate.

The 1999 landmark study that proposed the eGFR and included a coefficient for Black patients did so on the basis of 3 flawed, small, poor quality studies, Eneanya said, and these faulty assumptions were carried forward through later iterations. The study said that “previous studies have shown that on average, black persons have greater muscle mass than white persons” but that assertion relied on 3 small studies published in between the 1970s and 1990s.

One looked at the body composition of roughly 240 Black and White children and said that Black children had lower body fat and different body densities; the second looked at about 40 adults and said Blacks had higher total body potassium and calcium compared with Whites; and the third, looking at 60 healthy hospital workers, said that Blacks had higher on average serum creatinine kinase levels.

However, muscle mass on a living human cannot be measured, only on a cadaver, Eneanya noted; moreover, based on human genome studies, we know that there are no biological differences between races.

Sociodemographic differences in clinical trial participation, rather than race, are a more likely factor in variation, and those factors could affect creatine levels, she said. Possible explanations for differences in serum creatinine include muscle mass, excretion, ancestral, enzymatic, and transport processes, as well as diet, especially ones that include meat. Medications can also be a factor.

Pitfalls of Using Race in eGFR Equations

Although there are several criteria for recommending when a patient should be referred to nephrology specialty care, “most clinicians take the path of least resistance and they will use what is available to them and the easiest thing is an eGFR, even though the KDIGO [Kidney Disease: Improving Global Outcomes] guidelines say GFR,” Eneanya said.

But if the multiplication factor assigns black patients as having higher kidney function, then there will be delays in referral to nephrology specialty care, as well as kidney transplantation evaluation. The dosing of drug treatments can also be affected.

Given that implicit and explicit bias factors into provider communications and decisions, this could come into play as more Americans identify as mixed race and lead to less transparency in those recommendations, she cautioned.

There is no guidance for mixed race in the eGFR and there was a roughly 30% increase of individuals identifying as mixed race in the US Census between 2000 and 2010, and that number will keep increasing, Eneanya noted.

She cited a recent study that found that removing race as a factor in recommending care resulted one-third of Black patients reclassified to a more severe stage of CKD; this has implications for CKD management, referrals for kidney transplant specialty care, and dialysis access planning.

“And that speaks to, or supports the literature, that Black patients on average progress more quickly due to social and genetic reasons to kidney failure compared to other racial groups,” she said.

She did note the counterargument that removing the race qualifier could lead to an overdiagnosis of CKD, or to a patient receiving unnecessary dialysis or transplantation or lower doses of drug therapy.

But using race in eGFR equations fails 4 criteria she and others developed about when to justify using race in clinical care:

• The use of race provides a substantial benefit
• The benefit cannot be achieved through other feasible methods
• That patients who reject race categorization can be accommodated fairly
• The use of race is transparent

Physicians should look more at these “non-GFR” determinants of serum creatinine (generation, tubular handling, extrarenal elimination, muscle mass), she said.

She also called for alternative eGFR equations or other measures of kidney function without including race, such as cystatin C and cystatin C-Cr.

“False biological beliefs will absolutely affect clinical care,” she said later.