A Race-Free Approach to Diagnosing Chronic Kidney Disease
Posted on by Dr. Francis Collins
Race has a long and tortured history in America. Though great strides have been made through the work of leaders like Dr. Martin Luther King, Jr. to build an equal and just society for all, we still have more work to do, as race continues to factor into American life where it shouldn’t. A medical case in point is a common diagnostic tool for chronic kidney disease (CKD), a condition that affects one in seven American adults and causes a gradual weakening of the kidneys that, for some, will lead to renal failure.
The diagnostic tool is a medical algorithm called estimated glomerular filtration rate (eGFR). It involves getting a blood test that measures how well the kidneys filter out a common waste product from the blood and adding in other personal factors to score how well a person’s kidneys are working. Among those factors is whether a person is Black. However, race is a complicated construct that incorporates components that go well beyond biological and genetic factors to social and cultural issues. The concern is that by lumping together Black people, the algorithm lacks diagnostic precision for individuals and could contribute to racial disparities in healthcare delivery—or even runs the risk of reifying race in a way that suggests more biological significance than it deserves.
That’s why I was pleased recently to see the results of two NIH-supported studies published in The New England Journal of Medicine that suggest a way to take race out of the kidney disease equation [1, 2]. The approach involves a new equation that swaps out one blood test for another and doesn’t ask about race.
For a variety of reasons, including socioeconomic issues and access to healthcare, CKD disproportionately affects the Black community. In fact, Blacks with the condition are also almost four times more likely than whites to develop kidney failure. That’s why Blacks with CKD must visit their doctors regularly to monitor their kidney function, and often that visit involves eGFR.
The blood test used in eGFR measures creatinine, a waste product produced from muscle. For about the past 20 years, a few points have been automatically added to the score of African Americans, based on data showing that adults who identify as Black, on average, have a higher baseline level of circulating creatinine. But adjusting the score upward toward normal function runs the risk of making the kidneys seem a bit healthier than they really are and delaying life-preserving dialysis or getting on a transplant list.
A team led by Chi-yuan Hsu, University of California, San Francisco, took a closer look at the current eGFR calculations. The researchers used long-term data from the Chronic Renal Insufficiency Cohort (CRIC) Study, an NIH-supported prospective, observational study of nearly 4,000 racially and ethnically diverse patients with CKD in the U.S. The study design specified that about 40 percent of its participants should identify as Black.
To look for race-free ways to measure kidney function, the researchers randomly selected more than 1,400 of the study’s participants to undergo a procedure that allows kidney function to be measured directly instead of being estimated based on blood tests. The goal was to develop an accurate approach to estimating GFR, the rate of fluid flow through the kidneys, from blood test results that didn’t rely on race.
Their studies showed that simply omitting race from the equation would underestimate GFR in Black study participants. The best solution, they found, was to calculate eGFR based on cystatin C, a small protein that the kidneys filter from the blood, in place of the standard creatinine. Estimation of GFR using cystatin C generated similarly accurate results but without the need to factor in race.
The second NIH-supported study led by Lesley Inker, Tufts Medical Center, Boston, MA, came to similar conclusions. They set out to develop new equations without race using data from several prior studies. They then compared the accuracy of their new eGFR equations to measured GFR in a validation set of 12 other studies, including about 4,000 participants.
Their findings show that currently used equations that include race, sex, and age overestimated measured GFR in Black Americans. However, taking race out of the equation without other adjustments underestimated measured GFR in Black people. Equations including both creatinine and cystatin C, but omitting race, were more accurate. The new equations also led to smaller estimated differences between Black and non-Black study participants.
The hope is that these findings will build momentum toward widespread adoption of cystatin C for estimating GFR. Already, a national task force has recommended immediate implementation of a new diagnostic equation that eliminates race and called for national efforts to increase the routine and timely measurement of cystatin C [3]. This will require a sea change in the standard measurements of blood chemistries in clinical and hospital labs—where creatinine is routinely measured, but cystatin C is not. As these findings are implemented into routine clinical care, let’s hope they’ll reduce health disparities by leading to more accurate and timely diagnosis, supporting the goals of precision health and encouraging treatment of CKD for all people, regardless of their race.
References:
[1] Race, genetic ancestry, and estimating kidney function in CKD. Hsu CY, Yang W, Parikh RV, Anderson AH, Chen TK, Cohen DL, He J, Mohanty MJ, Lash JP, Mills KT, Muiru AN, Parsa A, Saunders MR, Shafi T, Townsend RR, Waikar SS, Wang J, Wolf M, Tan TC, Feldman HI, Go AS; CRIC Study Investigators. N Engl J Med. 2021 Sep 23.
[2] New creatinine- and cystatin C-based equations to estimate GFR without race. Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y, Crews DC, Doria A, Estrella MM, Froissart M, Grams ME, Greene T, Grubb A, Gudnason V, Gutiérrez OM, Kalil R, Karger AB, Mauer M, Navis G, Nelson RG, Poggio ED, Rodby R, Rossing P, Rule AD, Selvin E, Seegmiller JC, Shlipak MG, Torres VE, Yang W, Ballew SH,Couture SJ, Powe NR, Levey AS; Chronic Kidney Disease Epidemiology Collaboration. N Engl J Med. 2021 Sep 23.
[3] A unifying approach for GFR estimation: recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. Delgado C, Baweja M, Crews DC, Eneanya ND, Gadegbeku CA, Inker LA, Mendu ML, Miller WG, Moxey-Mims MM, Roberts GV, St Peter WL, Warfield C, Powe NR. Am J Kidney Dis. 2021 Sep 22:S0272-6386(21)00828-3.
Links:
Chronic Kidney Disease (National Institute of Diabetes and Digestive and Kidney Diseases/NIH)
Explaining Your Kidney Test Results: A Tool for Clinical Use (NIDDK)
Chronic Renal Insufficiency Cohort Study
Chi-yuan Hsu (University of California, San Francisco)
Lesley Inker (Tufts Medical Center, Boston)
NIH Support: National Institute of Diabetes and Digestive and Kidney Diseases
So! Words matter. When I saw this blog post title come up in my email, it was sort of click bait, bc honestly ‘Race-free’ anything is imagination. Racism is deeply embedded in healthcare. A ‘simple switch’ of a blood test or algorithmic equation is naive and harmful to suggest. Especially since kidney disease incidence specifically is a result of social determinants of health, and other historical exclusion and marginalization, not to mention mistrust of doctors and healthcare. So taken together, this title and the content of this post are even more egregious to that end. Not to mention, the bias inherent and built into artificial intelligence and algorithms is also harmful. This has to be better.
I have for a long time assumed that coming from a the tropics African kidneys are more avid in their reclamation of sodium and water. When exposed to the hypernatremic diet of the West, especially the US, they are at greater risk to develop HTN and renal-related pathology. They’ve only been here for 3-400 years which from an evolutionary perspective is no time at all — certainly not enough for their kidneys to adjust to a diet that is also becoming increasingly toxic for non-blacks. In the past 50 years the amount of sodium and sugars we put in the processed foods that people of lower socioeconomic status heavily rely on has more than doubled in a quest to create an artificial ugami called ‘the sweet spot’.
While improved access to healthcare is certainly part of the solution here, what is really needed is a complete shakedown of American Agrobusiness, which produces 3,600 cal/day — twice what any person needs!
If anything, the Africans who survived in this country had to be more avid in their reclamation of sodium and water because the White people who owned them often deprived them of both vital nutrients. It is not necessarily the Western diet but hundreds of years of abuse at the hands of Whites exerting evolutionary pressure and an unnatural selection.
Thanks for explaining in simple words how to diagnose Kidney Disease.
Thanks to Dr. Collins for this important update
Measurement of cystatin C instead of creatinine:
not to be overlooked also for us doctors who do not treat the nephrological field and sporadically we may encounter situations with incorrect evaluation.
I would like to express a reflection on the enzymatic diversity between individuals, both genetic and epigenetic.
I am also referring to differences within the same ethnic group, up to differences in the same parental group. An example, always in the topic of kidney pathology, is nephrolithiasis. problem that sometimes affects more than one person in the same family.
The expression of the disease in someone is mitigated by adequate nutrition and hydration.
Returning to the final result (CKD), enzyme systems have evolved over the millennia in relation to food availability and climatic conditions. Unfortunately today the overabundant and generalized supply of foods that overload the renal purification function, especially sodium chloride, produce daily disasters for health.
At first unaware, up to the irreparable damage over the years.
The simple quota limitation of the amount of sodium chloride in food productions would avoid a lot of health damage, with enormous savings in economic resources.
Less savory foods would not only be less palatable (so you eat less!) but, by causing less thirst, also reduce the intake of soft drinks (related to blood sugar: fewer people with diabetes).
Arterial hypertension, diabetic disease, renal insufficiency with relative transplant and related drugs, constitute a terrible danger to eye health: other heavy costs of human suffering and exponential economic impact.
– What we eat can be our luck or our misfortune-
CKD is frequently correlated to harmful dietary factors: in addition to the excess of sodium chloride, the overabundant presence of glutamate in foods is at stake.
Neurotoxic and ocular ( eg..in glaucoma ) damage from glutamate is know, as described in many studies, e.g.:
Inhibition of VDAC1 Protects Against Glutamate-Induced Oxytosis and Mitochondrial Fragmentation in Hippocampal HT22 Cells
“..The involvement of glutamate in neuronal cell death in neurodegenerative diseases and neurotrauma is mediated through excitotoxicity or oxytosis. The latter process induces oxidative stress via glutamate-mediated inhibition of cysteine transporter xCT, leading to depletion of the cellular glutathione pool. Mitochondrial damage, loss of mitochondrial membrane potential (MMP), and depletion of energy metabolites have been shown in this process. The Voltage-Dependent Anion Channel-1 (VDAC1)..”
Not only neuronal toxicity, renal damage from monosodium glutamate (MSG) has also been highlighted in several studies, e.g.:
https://pubmed.ncbi.nlm.nih.gov/32267892/
” A combination of monosodium glutamate and high-fat and high-fructose diets increases the risk of kidney injury, gut dysbiosis and host-microbial co-metabolism”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120859/
Worldwide flavor enhancer monosodium glutamate combined with high lipid diet provokes metabolic alterations and systemic anomalies: An overview
Few and healthy dietary rules would lead to better health and a large economic savings on a planetary scale, as the problem has no borders, especially in industrialized countries.
The kidney and the Covid19
In relation to the territorial context in which I work, the person who has Covid19 symptoms or who learns to be positive for a screening of tracking, for home cases the patient is advised to have a thermometer and oximeter for monitoring the
clinical picture, possibly also check blood pressure and blood sugar (if previously connected ).
It does not seem to me that even the simple urinalysis is recommended, which is cheap and can be performed at home.
In fact, through a strip that is immersed in urine, after 1-2 minutes we can obtain, for example, about 10 parameters.
They indicate not only kidney damage (presence of proteins, red blood cells, white blood cells, nitrites for urinary infections) but also important systemic metabolic indices: pH, urinary density, glycosuria and ketonuria indicate whether metabolic decompensations are in progress; finally also bilirubin and urobilinogen, for what concerns the liver or eventual haemolytic anemia.
I say this because unfortunately Covid19 can also compromise the kidney system, as well as a series of complications with a sneaky onset, not always quickly diagnosed.
Thank you for your attention and … I apologize if I took up too much space.
Thank you, Dr. Collins, for this article. This work will help the kidney patient to diagnose his/her problem better.