Shortcomings of the current standard of kidney care

The problem with eGFR equations that rely on race as a surrogate for muscle mass 

Estimated glomerular filtration rate (eGFR) is the primary diagnostic parameter used to detect and manage kidney disease. The current standard of care is to use serum concentrations of creatinine, a by-product of muscle metabolism, to calculate eGFR¹. This means that the equations that use creatinine to estimate glomerular filtration rate must be adjusted for a patient’s muscle mass².

Traditionally, this has been achieved by using race as a surrogate for muscle mass, because previous studies have claimed inherent differences in body composition between blacks and whites³. While those who have grown accustomed to using creatinine over the past few decades have suggested simply removing the race adjustment factor from the aforementioned equations, it is unclear what the implications of such a move would have on eGFR accuracy and clinical decision making.

A new chapter for kidney care in America

In the US there have recently been discussions about the race component of creatine equations. A disproportionate number of the 37 million Americans that have kidney disease are African Americans, Latinos, American Indians, Asian Americans, or Pacific Islanders⁴. The use of race in clinical algorithms used to detect and manage kidney disease in these groups have contributed to major kidney-health disparities.

In a joint statement made by the American Society of Nephrology and the National Kidney Foundation on March 9^th of this year, the groups’ leaders affirmed that⁵:

1. “Race modifiers should not be included in equations that estimate kidney function.”
2. “Current race-based equations should be replaced by a suitable approach that is accurate, inclusive, and standardized in every laboratory in the US.”

The hope is that clinical implementation of equations that provide an unbiased assessment of kidney function would allow health professionals to ensure equitable outcomes in all patients with kidney disease.

Cystatin C based eGFR is independent of muscle mass and race

Fortunately, there is an alternative biomarker that is already being used in many hospitals around the world. Cystatin C is ubiquitously expressed through all nucleated cells¹. Individuals with similar kidney function can therefore be expected to have similar serum concentrations of cystatin C. This means that equations used for calculating GFR do not depend on an individual’s muscle mass or race.

Consequently, cystatin C is also considered the preferred marker for eGFR in patient groups with significant variability in muscle mass:

• Children⁶
• Athletes⁶
• Seniors⁶
• Amputees⁷
• Patients with spinal cord injuries⁸
• Patients with conditions linked to malnutrition⁷

Clinical adoption of cystatin C may well present the opportunity to “replace current race-based equations with a suitable approach that is precise, inclusive and standardized in every laboratory in the United States.”⁴

Contact us for more information

Do you want to know more about cystatin C, our assay or how to implement cystatin C in your laboratory? Please fill out the form below or send an email to marketing@gentian.com.

References 

1. Mussap M, Plebani M. Biochemistry and clinical role of human cystatin C. Crit Rev Clin Lab Sci. 2004;41(5-6):467-550.

2. Grubb A. Cystatin C is Indispensable for Evaluation of Kidney Disease. EJIFCC. 2017;28(4):268-276. Published 2017 Dec 19.

3. Dale R Wagner, Vivian H Heyward. Measures of body composition in blacks and whites: a comparative review. The American Journal of Clinical Nutrition, Volume 71, Issue 6, June 2000, Pages 1392–1402

4. Kidney disease: The basics. (2020, May 15). Retrieved March 10, 2021, from 

5. Removing race from estimates of kidney function. (2021, March 10). Retrieved March 10, 2021, from www.kidney.org/news/removing-race-estimates-kidney-function 

6. Ebert N, Shlipak MG. Cystatin C is ready for clinical use. Curr Opin Nephrol Hypertens. 2020 Nov;29(6):591-598. 

7. Aakjær M, Houlind MB, Treldal C, et al. Differences in Kidney Function Estimates Based on Creatinine and/or Cystatin C in Non-Traumatic Amputation Patients and Their Impact on Drug Prescribing. J Clin Med. 2019;8(1):89. Published 2019 Jan 14.

8. Jenkins MA, Brown DJ, Ierino FL, Ratnaike SI. Cystatin C for estimation of glomerular filtration rate in patients with spinal cord injury. Ann Clin Biochem. 2003;40(Pt 4):364-368.