Prof. dr. Hans Pottel

New Kidney Function Equation Works Independent of Sex and Race Interview with:

Prof. dr. Hans Pottel

Prof. dr. Pottel

Prof. dr. Hans Pottel
KU Leuven Kulak
Department of Public Health and Primary Care
Belgium What is the background for this study?

Response:  The glomerular filtration rate (GFR) is used to diagnose patients with chronic kidney disease and is also used to adjust the dose of drugs that are eliminated by the kidneys. An accurate estimation of GFR is considered of importance in the management of kidney health in patients. In 2021 we published a new serum creatinine based equation, called the European Kidney Function Consortium (EKFC) equation (Pottel H. et al, Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate : A Cross-sectional Analysis of Pooled Data. Ann Intern Med (2021) 174: 183-191):

EKFC-eGFR = 107.3 / [Biomarker/Q]a x [0.990(Age – 40) if age > 40 years]

With a = 0.322 if Biomarker/Q is less than 1, and a = 1.132 if Biomarker/Q is 1 or more.

The equation can easily be interpreted: the leading coefficient equals the glomerular filtration rate (GFR) of 107.3 mL/min/1.73m², which is the average GFR in healthy children (aged > 2 years), adolescents and young adults. The average healthy GFR remains constant until the age of 40 years, and starts decreasing beyond that age. The GFR is inversely related to the ‘rescaled’ biomarker. The rescaling factor (Q) is the average biomarker value for healthy people of a specific population (e.g. children, adult men, adult women, white people, black people, …). Biomarker/Q equals ‘1’ for the average healthy person, corresponding with eGFR = 107.3 mL/min/1.73m² (up to 40 years of age).

It should be noted that for serum creatinine, the Q-value depends on sex and race.

Our hypothesis was that the above equation is valid for any renal biomarker, on the condition that the biomarker is appropriately scaled. We showed that the same equation was able to estimate GFR from 2 years to oldest ages.

In the current study we tested and validated our hypothesis by applying the above formula for appropriately ‘rescaled’ cystatin C. What are the main findings? Is there a practical advantage to the Cystatin-C based equation over eGFR, especially since the sex and race of patients are known? 

Response: The main finding is that the above equation indeed works very well for appropriately rescaled cystatin C, with a scaling factor Q independent of sex and race. Our cystatin C based EKFC-equation can thus be used in Black and White patients, men and women, and potentially in patients of mixed ethnicity, in transgender patients, etc. Moreover, the equation can easily be extended to children by defining the scaling factor Q (which will be done soon in future research). This will make the equation applicable for all ages, avoiding implausible jumps at the transition between pediatric nephrology care and adult nephrology care. Does this equation have a cost advantage/disadvantage?

Response: Currently the cost for cystatin C is about 10 times the cost for serum creatinine. In many countries the cost for cystatin C is not reimbursed by the social security agency. We are convinced that the current study might be a game changer. Is there anything else you would like to add? Any disclosures?

Response: There is a variety in the quality of assays used to measure creatinine and cystatin C. One important requirement of our study was that serum creatinine was obtained with assays that were calibrated directly to the gold standard Isotope Dilution Mass Spectrometry method. For cystatin C all assays were calibrated against the international certified IFCC standard. Therefore, the current equation is only valid for high quality measurements of the biomarkers.

One other important remark is that we included data from Black people in Europe and Africa, but we did not have high quality measurements of the biomarkers for African Americans. Therefore, the performance of our new cystatin C based equation should still be demonstrated in African Americans.


Cystatin C–Based Equation to Estimate GFR without the Inclusion of Race and Sex

Hans Pottel, Ph.D., Jonas Björk, Ph.D., Andrew D. Rule, M.D., Natalie Ebert, M.D., M.P.H., Björn O. Eriksen, M.D., Ph.D., Laurence Dubourg, M.D., Ph.D., Emmanuelle Vidal-Petiot, M.D., Ph.D., Anders Grubb, M.D., Ph.D., Magnus Hansson, M.D., Ph.D., Edmund J. Lamb, Ph.D., Karin Littmann, M.D., Ph.D., Christophe Mariat, M.D., Ph.D., 

N Engl J Med 2023; 388:333-343
DOI: 10.1056/NEJMoa2203769
January 26 2023

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