Tag: Race

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What is missing from the race and eGFR discussion

The ASN and NKF have a joint task force working toward a response to the race and eGFR problem and they are now inviting people to submit oral and written testimony. I signed up. Hopefully I get an opportunity, but suspect there will be too many people for them to hear even a fraction of the applicants.

I have been thinking about race and eGFR and this is where I am at…

  • Race is a social not a biological construct
  • People identified as black (or self-identified as black) have higher measured GFR for the same serum creatinine as non-blacks
  • These higher eGFR results in black people (self-identified or not), a marginalized group and a population already at increased risk of adverse kidney outcomes, being denied transplant listing and CKD referral.

But what is not ever seem to be questioned in this discussion is the perverse use of estimated GFRs to make critical binary decisions in individual patients. The eGFR equations are amazing how well they predict GFR for groups of patients with minimal bias, but their reliability in an individual is stunningly imprecise. Accuracy in individual patients is measured by P30, the likelihood that the true value will be within 30% of the measured value. The P30 is 84% with CKD-Epi, a bit better compared to the 80% in MDRD. This means that for the critical decision of whether to list a patient for a kidney transplant, a patient with an eGFR of 21 will have an actual measured GFR somewhere between 15 and 27 in 84% of cases. This 30% spread is greater than the 16% adjustment for black race.

Though using race for eGFR should be stopped, and we can do that today by making cystatin-c the coin of the realm, this doesn’t change the problem of over indexing on eGFR for individual patient decisions. Cystatin C is no better than creatinine in providing a precise estimate in eGFR (P30 86%). Decisions like transplant listing and CKD referral should not rely on a measurement with so much uncertainty. We report eGFR on lab reports but give physicians no sense of the imprecision hidden in that number.

I think if eGFR were reported as a range (±30%), we would stop using sharp cut-off limits for critical decisions like transplant and referral.

The use of sharp cutoff for decisions like transplant and CKD referral harms all patients with CKD, not just black people. We should immediately to remove race from eGFR calculations by standardizing cystatin-C as the way to assess eGFR but at the same time we should start the process of unwinding guidelines and individual patient decisions from being wedded to inaccurate estimates of GFR.

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Is estimated GFR racist?

Update from January 2021: This is an old post and I have evolved my thoughts on this issue. I leave this here mainly as bread crumb on the trail of my evolving thoughts about this topic.

 

 

Zachery Berger published this epic tweet storm last week about estimated GFR. It starts here:

The conclusion is that using race in the MDRD formula (and by extension the  CKD-epi formula) is inherently racist.

I do not think this is the case. Trying to estimate GFR from a serum creatinine and a few demographic variables is impossible, the best we can hope for is a reasonable guess. To see how bad we are take a look at the wide variability at high GFRs with the current CKD-Epi formula:

So that GFR of 60 has a 95% CI of being between 35 ml/min and 92 ml/min. Not so reassuring.

One of the primary reasons for this imprecision is that creatinine production varies from body to body. When one person produces more creatinine than another, for a set rate of creatinine excretion his serum creatinine concentration (what we measure on a blood test) will be higher. Who produces more creatinine? People with more muscle mass.

  • Larger people produce more creatinine than smaller people
  • More muscular people produce more creatinine than less muscular people
  • People with four limbs produce more creatinine than people with 3 limbs
  • Men produce more creatinine than women, on average
  • Young people produce more creatinine than older people, on average
  • Vegetarian Indians produce less creatinine than westerners
  • Black people produce more creatinine than non-black people, on average

The data is shown in figure 1 of Levey’s 1999 study.

Even though Dr. Berger did not draw the conclusion that estimated GFR is inherently sexist, let’s look at gender first. I have recolored the two graphs and superimposed them on one another. Men are in red and women are in blue:

It is clear that for any given GFR the men tend to have a higher creatinine than the women. This is not perfect and it is not hard to pick out individuals where this generalization fails, but in general this is a fair generalization. Levey comments and quantifies this gender difference:

At any given GFR, the serum creatinine concentration is significantly higher in men than in women (P 0.001).

The figure, without any recoloring, provides the curves for black (solid line) compared to non-black (dotted line) patients. Again it is clear that the average GFR is higher for black patients at any set creatinine. Levey comments and quantifies the racial difference:

At any given GFR, the serum creatinine concentration is significantly higher in men than in women and in black persons than in white persons (P=0.001).

Dr. Berger misses this fact:

How do we know *that* to be true? BECAUSE THEY MEASURED IT!

The refernces are just there to show that this is not a new and novel finding. This was an expected finding. The study does not rest on these references. The investigators in the MDRD study measured the serum creatinine, GFR, and asked patents if they were white, black or hispanic. The data shows that black people had, on average, 18% higher GFR for any measured creatinine. The fact that the prior work on this subject was deplorable does not alter the findings.

Berger is so upset that the estimated GFR differentiates black and white people that he misses the real problem with the MDRD study, the embarrassing lack of black people in the original data set. Only 12% of that cohort was African American, less than 200 people. A group that has the greatest incidence of end-stage kidney disease should be over-represented in a study about reducing the progression of CKD, not under-represented. Remember, Levey was using the data already collected for the Modification of Diet on Renal Disease study. This was not de novo data collected for the purpose of generating this equation. This weakness was corrected in the CKD-Epi equation where there were nearly 3,000 African Americans representing 30% of the cohort. The adjustment for race went from an 18% bump in GFR for a given creatinine down to 15.9%. Not much difference.

We use race, gender, and age not because we are racists, sexists, and agists, but rather because there are physiologic differnces between the races, the genders, and the aged. We exploit those differences to improve the accuracy of our estimate. All of these adjustment are just attempts to use demographic variables to squeeze a better correlation of GFR from a serum creatinine.