Volume 35 Number 3 | June 2021

Patient Safety Corner

Rose Hanna, DCLS, MS, MLS(ASCP)CM, ASCLS Patient Safety Committee

Rose HannaKidney function is best determined by the glomerular filtration rate (GFR); however, it is challenging to measure directly and is not practical for routine physician office visits. Consequently, equations such as Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) were developed to use measurable variables to provide an estimated glomerular filtration rate (eGFR).

The Cockcroft-Gault formula was developed in 1973 for estimating creatinine clearance and was based on age, weight, and sex. However, it is no longer recommended since the equation did not use standardized creatinine measurements. This led to inaccurate results and inappropriate medication dosing.1

The updated equations (MDRD and CKI-EPI) for estimating kidney function use standardized serum creatinine values along with three demographic variables: age, sex, and race. Race became part of the equation based on the assumption that African Americans have greater muscle mass, yielding a higher serum creatinine value. However, there is debate about the use of race and that it is not a standardized variable.

For more on this topic, see the ASCLS recorded webinar, “Controversies in Nephrology: Reconsidering Race and eGFR,” presented by Nwamaka Eneanya, MD, MPH, FASN, on March 25, 2021.

Race is now viewed as a social concept rather than biological. Race does not provide an accurate measurement since there is diversity within the African American community and in patients who self-identify as multiracial; currently, there are no set criteria for individuals of mixed race in evaluating the eGFR.2 Race is also subject to bias since it may be assigned by the physician based on skin color or self-reported by the patient.

Therefore, the question is being asked: “Is using the race coefficient contributing to patient harm?” If we take a hypothetical 67-year-old male patient with a serum creatinine level of 3.5 mg/dL, and the patient identifies as white, using the MDRD equation the eGFR will be 18 mL/min/1.73 m², compared to 21 mL/min/1.73 m² for a black patient. Referral for transplant evaluation occurs when the eGFR is less than 20 mL/min/1.73 m². Consequently, the overestimation in eGFR due to adjusting for race using the MDRD or CKI-EPI equation may contribute to delays in preventive care or referral for a kidney transplant.3 The difference in using the race coefficient may be less meaningful in healthy individuals, but it has a significant role in patients with CKD.

The use of eGFR drives important clinical decisions, such as referral to a nephrologist, medication dosing, initiation of dialysis, and candidacy for kidney transplant list. For these reasons, the most accurate information should be provided. Therefore, in order to improve patient safety, biomarkers that are independent of muscle mass, such as Cystatin C instead of serum creatinine, or directly measuring GFR to guide the critical decision of kidney transplant eligibility, should be considered.

The assumption that African Americans have higher muscle mass is a misleading statement, especially when evaluating elderly or frail black patients with CKD. So, instead of concentrating on race as a factor to adjust the equations, we should consider social factors that contribute to health outcomes and the use of race-independent measures to make important medical decisions.

References

  1. National Kidney Foundation. Cockcroft-Gault Formula. 2021. Available at: https://www.kidney.org/professionals/kdoqi/gfr_calculatorcoc
  2. National Kidney Foundation. Race and eGFR: What is the Controversy? 2021. Available at: https://www.kidney.org/atoz/content/race-and-egfr-what-controversy
  3. Zelnick LR, Leca N, Young B, Bensal N. Association of the Estimated Glomerular Filtration Rate With vs. Without a Coefficient for Race with Time to Eligibility for Kidney Transplant. JAMA Network Open. 2021; 4(1): e2034004.

Rose Hanna is a Doctor of Clinical Laboratory Science.