Routine bloodwork at your doctor’s visit usually includes an assessment of kidney function, something called the estimated glomerular filtration rate (eGFR). If you have looked at your results, you might have noticed two rows, one result for African Americans and one for non-African Americans. Here are my lab results:
Portion of author's Basic Metabolic Panel
Note that as a non-African American, my eGFR is 98, but would be 113 if I were African American. What are African American kidneys doing differently?
The eGFR is just an estimation of the actual GFR, a precise measurement of how well your kidneys are doing their primary jobs of filtering your blood and excreting waste products into the urine. Individuals with kidney failure have low GFRs. If the GFR is low enough, the person will need artificial blood filtering – also known as dialysis.
Measuring actual GFR is time consuming and cumbersome. The gold standard involves an injection of inulin, a polysaccharide not normally found in humans’ bloodstreams, with multiple blood and urine tests over several hours to quantify the rate of filtration of this substance. But most people will never have an inulin GFR test done. Instead, their kidney function will be estimated using creatinine, a much simpler test. This is what is included on your routine bloodwork panel and it is how the eGFR is calculated. Creatinine is a waste product from muscle that is excreted into the urine. We all make creatinine, and if our kidneys are functioning, they are filtering creatinine at a constant rate. Blood levels of creatinine turn out to be a relatively good measure of how well our kidneys are filtering – in general, if the creatinine is rising, kidney function is declining.
Creatinine: a muscle breakdown product used to estimate kidney function
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Creatinine levels are not a perfect approximation of kidney function, though, since individuals differ in the amount of creatinine they produce. The more creatinine someone makes, the higher her creatinine level, even if her kidneys are working fine. Creatinine comes from muscle, so more muscular individuals release more creatinine and have overall higher creatinine levels than scrawny individuals. Men, as a group, tend to have a higher muscle mass than women, so they also tend to have higher creatinine levels. Elderly individuals, who have lost muscle mass with aging, tend to have lower creatinine levels. If we want to estimate kidney function based on creatinine, we need to correct for muscle mass. Accurately measuring muscle mass is another cumbersome procedure, so instead, we use generalizations and correct for them: the formula for calculating eGFR thus uses gender and age as a gross correction for muscle mass. We assume that younger people and males will have higher creatinine levels at baseline.
The guy on the right will have higher creatinine levels - and a lower estimated GFR
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But it turns out that even when accounting for gender and age, our formula for calculating eGFR from creatinine levels is not perfect. One reason is that different geographic and ethnic groups seem to have different baseline levels of creatinine. The first estimated GFR was developed by Cockcroft and Gault in the 1970s – they showed that blood levels of creatinine could be used to estimate creatinine clearance, which correlated with GFR.[1] Unfortunately, the study included only white people (and mostly men), so it was not clear whether their model would extend to everyone. When later tested in people who self-identified as Black, creatinine levels were correlated with GFR, but at different levels than in those who self-identified as white individuals. That is, Blacks had higher creatinine levels, on average, for any given GFR. For many years this was assumed to be due to increased muscle mass in Blacks, something that has been documented in many studies, but this explanation may be inadequate.[2] Whatever the reason, it does appear that when considering self-described Blacks as a whole, Blacks do have higher creatinine levels than non-Blacks with the same renal function.
As a result of this, researchers decided to start factoring in race when calculating the estimated GFR. In 1999 the Modification of Diet in Renal Disease study proposed a new estimated GFR formula, now called the MDRD equation.[3] This equation included age and gender, like the Cockcroft-Gault formula, but also included Black ethnicity, and seemed to produce a more accurate picture of kidney function (at least in their study population). Another big update came in 2009, when the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) released their own formula, which used the same variables as the MDRD model, but with some modifications in order to make it more accurate for those with normal kidney function (MDRD had only looked at those with kidney disease).[4] The CKD-EPI and MDRD equations are now the most common methods of estimating GFR from creatinine level – these are the ones used to give you the eGFR on your lab slip.
The formulas require age and gender, which are usually included in the lab requisition, so the lab can plug those into the formula for calculating eGFR. Since ethnicity and race are usually not given to the lab, it has to give two eGFRs, one for African Americans and one for non-African Americans (what was called Black ethnicity in the studies has become African American on most lab results, ignoring the different meanings of these terms).
In the last few years physicians have started questioning the use of race in GFR estimation. One reason is that race and ethnicity are not limited to Black and non-Black. Multiple geographic and ethnic groups appear to have different normal ranges for creatinine, leading to inaccurate eGFRs unless another correction for race is made. And not all Blacks need the “Black equation”: Black African adults living in Africa seem to have a more accurate eGFR when using the “non-Black” equation. [5]
African American and non-African American kidneys look the same - and they all look surprisingly like kidney beans.
Photo by Engdao at bigstockphoto.com.
Another reason for questioning the use of race in the equation centers on treating what is essentially a social construct (race) as an objective physiologic truth. There is no gene for “Black.” And whether someone defines herself as Black (or African American) is heavily influenced by culture. Many of us have mixed genetic backgrounds. Does someone with a Black mother and white father count as Black, white, both, or something else? And which eGFR equation should he use? There are numerous ethnicities that do not fit neatly into Black vs. non-Black. And there are numerous ethnicities within the broad category of Black – why include such imprecise categorization into a medical equation?
Finally, using a race-corrected formula may lead to worse care for African Americans. Many clinical decisions rest on the eGFR. We diagnose chronic kidney disease, determine medication dosages, and decide when to refer to a specialist all based on eGFR. When using the race correction for eGFR, an African American will be assigned a higher (better) GFR than a white person with the same creatinine. In cases that are near the cutoffs for referral, it may be that the white person is referred to a specialist when the African American is not, even though they have the same creatinine levels. eGFR also determines who can be referred for a kidney transplant. Again, if the eGFR levels are close to the cutoff for referral, then the white person will be referred for a transplant before the African American. All of this is fine if the calculated eGFR is an actual representation of kidney function. But given that we see variations in creatinine ranges even within different “African American” populations, can we legitimately assume that every African American patient is best served by the African American equation?
If the answer is not a solid "yes", then we probably should not use race in our estimation of GFR.
Earlier this year, the University of Washington Department of Medicine decided to stop using race in eGFR calculations, after medical students began questioning the practice. Their solution was just to remove race from the formula, keeping age and gender, and continue to use creatinine levels. Unfortunately, the discrepancies in creatinine levels between ethnicities and geographic areas persists, compromising the accuracy of any formula using creatinine.
A better solution would use something other than creatinine. The protein cystatin C is one candidate that is already used in some circumstances. Unlike creatinine, it is not as influenced by muscle mass or ethnicity, but currently it is not widely available and is more expensive. Studies on its accuracy have been mixed, and we don’t yet have enough evidence that it works better than creatinine overall. [6] For now, creatinine may be the best we have, but with increased awareness of race issues in health, this will likely change. African Americans and non-African Americans both need a better method of tracking kidney function.
[1] Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.
[2] Hsu J, Johansen KL, Hsu CY, et al. Higher serum creatinine concentrations in black patients with chronic kidney disease: beyond nutritional status and body composition. Clin J Am Soc Nephrol. 2008;3(4):992-997.
[3] Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461-470.
[4] Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate [published correction appears in Ann Intern Med. 2011 Sep 20;155(6):408]. Ann Intern Med. 2009;150(9):604-612.
[5] Bukabau JB, Sumaili EK, Cavalier E, et al. Performance of glomerular filtration rate estimation equations in Congolese healthy adults: The inopportunity of the ethnic correction. PLoS One. 2018;13(3):e0193384. Published 2018 Mar 2.
[6] Scarr D, Bjornstad P, Lovblom LE, et al. Estimating GFR by Serum Creatinine, Cystatin C, and β2-Microglobulin in Older Adults: Results From the Canadian Study of Longevity in Type 1 Diabetes. Kidney Int Rep. 2019;4(6):786-796. Published 2019 Feb 21.
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