For years, the estimation of glomerular filtration rate (GFR) has been based largely on creatinine-based equations that assumed — inaccurately — better renal function in Black patients. As a result, Black adults, though at a higher risk for chronic kidney disease (CKD) progression and end-stage kidney disease (ESKD), have received less timely treatment based on a commonly used measurement that incorrectly overestimates their kidney function. To remedy this example of a health disparity, nephrologists have sought ways of estimating GFR without including a race variable. The idea is that doing so would provide a more accurate estimate of kidney function and eliminate bias between racial groups.
The primary function of the kidneys is to maintain fluid and electrolyte balance and to remove waste products from the body. Knowing how well the kidneys are functioning may affect medication dosing and other clinical decisions such as when to be evaluated for kidney transplantation. If kidney function starts to deteriorate, waste products build up and have deleterious effects on other organ systems (for example, contributing to heart disease or other chronic conditions). In some cases, reduced kidney function may progress to ESKD, requiring dialysis or a kidney transplant to stay alive.
GFR is the measure used to assess how well the kidneys function. This value is often part of a routine lab panel obtained during clinical visits. Since measuring GFR directly is complicated, clinicians estimate it using a variety of equations and then use these estimates to inform clinical decisions. CKD, for example, is diagnosed when GFR or estimated GFR is below 60 mL/min/1.73 m2.
The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, recommended by Kidney Disease Improving Global Outcomes (KDIGO), is often used by laboratories. It is based on serum creatinine level, sex, age, and race. Though it is generally considered to be an accurate estimation in most people, it is now recognized to overestimate GFR in Black people. So, if a Black patient and a patient who is not Black have the same actual kidney function (by directly measuring GFR), the CKD-EPI calculation will produce a higher estimated GFR for the Black patient. If the Black patient’s kidney function is categorized as higher/better than it actually is, they may not receive an appropriate diagnosis of CKD, leading to delayed treatments and possibly worse clinical outcomes.
For patients with moderately impaired kidney function, an inaccurately overestimated GFR may mean the difference between starting and stopping specific medications and delayed referral to a nephrologist. For patients with severely impaired kidney function, it could lead to delays in kidney transplantation and greater risk for complications of CKD.
All creatinine-based equations estimating GFR have significant variability that can lead to error. Many factors affect serum creatinine concentration, including body size, body composition, dietary intake (especially meat), physical activity, medications, and comorbidities. Therefore, alternative markers to allow estimated GFR have been developed and cystatin C is the most studied alternative. Cystatin C is a protein found in the blood that becomes elevated when GFR is reduced. Although cystatin C has its own caveats (as do all laboratory tests), it can provide another estimate of GFR. KDIGO recommends that cystatin C be used for confirmatory testing in adults with estimated GFR < 60 mL/min/1.73 m2 and recent studies indicate that equations to estimate GFR that use both creatinine and cystatin C are more accurate than those that use only one variable.
The medical community, specifically the National Kidney Foundation/American Society of Nephrology Task Force, has acknowledged inequities resulting from the use of the race-based GFR equation. They have refitted the CKD-EPI equations (both with and without cystatin C) to estimate GFR without using race as a variable, resulting in a more accurate estimate. Two recent studies using the revised equations noted greater accuracy in GFR estimates for Black patients and patients who are not Black (Inker et. Al. and Hsu et.al.). The new equations classified a greater number of Black individuals as having more severe CKD, which should, in turn, reduce racial disparities in medical care.
