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October 5, 2021
Test may help reduce racial disparities in kidney disease
At a Glance
- Researchers found that measuring levels of a protein called cystatin C can accurately estimate kidney function without needing to take race into account.
- A race-blind method for estimating kidney function could help reduce racial bias in classifying chronic kidney disease, which can affect the timing of treatments.
More than 37 million people in the U.S. are thought to be living with chronic kidney disease, or CKD. In this condition, the kidneys can’t filter blood the way they should. CKD may eventually lead to kidney failure, which is fatal without life-long dialysis or a kidney transplant.
CKD tends to progress slowly over time, but its speed of progress varies between people. When it first develops, it often has no symptoms. While the condition can’t be cured, steps can often be taken to prevent it from quickly growing worse.
Kidney function (also called glomerular filtration rate, or GFR) can be directly measured, but the procedure is complex and time-consuming. Simple blood tests are now routinely used to estimate kidney function and screen for CKD. The most common one measures levels of a protein called creatinine. Creatinine is a waste product normally produced by muscles cells and filtered out by the kidneys.
Formulas are used to estimate kidney function based on blood creatinine levels. However, for reasons that aren’t clear, Black people in the U.S. tend to have higher levels of creatinine in their blood. To account for this difference and provide a more accurate estimate of kidney function in Black people, kidney function estimates currently include race as a variable.
But much diversity exists among self-reported racial groups, which are not based on biology. Researchers have raised concerns that race-based equations may result in misclassification and contribute to disparities in CKD treatment and outcomes. Black Americans, for example, are at higher risk of kidney failure than white Americans.
Two research groups tested whether measuring a different protein produced by the kidneys, cystatin C, could create a race-blind estimate of kidney function. Both groups were funded primarily by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results were published on September 23, 2021, in the New England Journal of Medicine.
One team, called the Chronic Renal Insufficiency Cohort, tested whether several equations including or omitting race could more accurately estimate kidney function than standard ones based on creatinine levels. They examined records of more than 1,200 people who had their GFR directly measured.
When the team removed race from a standard equation used in the clinic, its accuracy dropped; it underestimated kidney function in Black patients and was less accurate overall. However, when they used cystatin C levels instead of creatinine, the estimates were accurate regardless of whether race was included.
The second team, the Chronic Kidney Disease Epidemiology Collaboration, examined data from more than 17,000 people to examine and test equations. They created new equations to estimate kidney function that omitted race but used combinations of creatinine and cystatin C levels. In their analysis, dropping race from the standard equations led to underestimation of kidney function in Black patients. One of the equations also overestimated it in white patients.
In contrast, a new equation that used both creatinine and cystatin C but not race was most accurate. The team estimated that the overall prevalence of CKD among Black Americans would be higher if cystatin C was regularly measured. This suggests that many Black patients with CKD are currently not receiving needed treatment.
“An accurate [kidney function] formula that does not rely on self-reported race is a huge leap forward for all people with, and at risk for, chronic kidney disease,” says NIDDK director Dr. Griffin P. Rodgers.
Cystatin C testing is currently not as widely available as creatinine testing. Efforts to increase its availability and reduce its cost will be needed before it could be widely adopted as an estimate of kidney function.
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References: 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. doi: 10.1056/NEJMoa2103753. Online ahead of print. PMID: 34554660.
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. doi: 10.1056/NEJMoa2102953. Online ahead of print. PMID: 34554658.
Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR), and National Institute of General Medical Sciences (NIGMS).