EKFC Equation Calculator for Glomerular Filtration Rate (GFR)

EKFC Equation Development

Glomerular filtration rate (GFR) is estimated in clinical practice from equations based on the serum concentration of endogenous biomarkers and demographic data. There are several equations available, requiring diverse variables and with different limitations attached to them, from the Cockcroft-Gault, MDRD equations and the CKD-EPI₂₀₀₉ to the more recent CKD-EPI_Cr2021.

The European Kidney Function Consortium (EKFC) equation published in 2021 is a modified version of a previous FAS equation, that combines design features of the FAS and CKD-EPI equations. It was aimed at addressing the limitations of previous eGFR equations, mainly in the transition from adolescence to adulthood and overestimation of GFR in young adults.

That EKFC equation was applicable to ages 2-90 years and serum creatinine (0.45 to 5.54 mg/dL) and demonstrated fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations. It was however limited by the fact that neither the development nor validation data sets didn’t include Black patients.

Serum creatinine was measured using IDMS-traceable assays, and GFR was assessed with various established reference methods, primarily iohexol plasma clearance. This equation represents an advancement of the earlier Full Age Spectrum equation, with the aim of addressing the limitations of the bedside Schwartz and CKD-EPI equations, particularly in terms of age and race modeling.

The age variable is modelled so that it guarantees continuity at the transition between pediatric and adult nephrology care and to better match with the well-documented decline in GFR starting at 40 years.

The 2021 full age spectrum EKFC equation and the Q values (corresponding to the median SCr values for the age- and sex-specific populations) are summarised below:

eGFR by EKFC_Creat

Within more recent studies, the EKFC_Creat incorporates median normal value of serum creatinine in healthy population and overcomes the limitations of the CKD-EPI equations: it provides a continuity of eGFR at the transition between pediatric and adult care, and performs reasonably well in diverse populations, assuming dedicated scaling of serum creatinine (Q) values is used. Q_creat is the median normal value of serum creatinine in a given population.

A recent study on United States cohorts considered two strategies with population-specific Q-values in Black and non-Black men and women (EKFC_PS) or a race-free Q-value (EKFC_RF). The percentage of estimated GFR within 30% of measured GFR was similar for CKD-EPI₂₀₂₁ (79.2% [78.5%; 79.9%]) and EKFC_RF (80.1% [79.4%; 80.7%]), but improved for the EKFC_PS equation (81.1% [80.5%; 81.8%]).

The authors concluded on that occasion that their EKFC equations can be used to estimate GFR in the United States incorporating either self-reported race or unknown race.

The rescaling factors for serum creatinine (Q_Creat) are the median biomarker value among healthy populations: White and Black (Africa and Europe), summarised in the table below:

The EKFC_Creat equations are:

The EKFC_Creat was shown to perform better in young adult population (before 30 years of age) and slightly better in old people. The EKCF_Creat estimated GFR performs well in diverse populations when the dedicated Q values are used.

The absolute differences between the two equations are minimal when CKD-EPI values are below 30 mL/min/1.73 m². For nearly all patients with CKD-EPI values under 45 mL/min/1.73 m², the differences remain well under 5 mL/min/1.73 m². The largest absolute differences are seen in very young and elderly patients with well-preserved kidney function, where EKFC values are notably lower than those of CKD-EPI.

eGFR by EKFC_CC

In 2023, a version of the EKFC that replaces serum creatinine with cystatin C has been published following a validation study in cohorts of White patients and Black patients in Europe, the United States and Africa.

The EKFC_CC is based on median cystatin C value in the general population, found to be independent of sex and ethnicity, and was found to perform better than the CKD-EPI equation based on cystatin C. The Q value for cystatin C (Q_CC) was determined following a study on a large database from Sweden (227,643) where cystatin C is measured in daily practice.

Further matched analysis showed that cystatin C concentrations were not different between Black and non-Black European individuals, therefore, in contrast to the population requirement of serum creatinine, cystatin C may be employed to a formula that is sex (only slight difference between males and females, accounted for by median value) and race-free.

Whilst the EKFC_CC retains the same mathematical form as the EKFC_Creat , in contrast to the latter where the scaling factor for serum creatinine may be population and sex dependant, here the rescaling factor for cystatin C (Q_CC) was estimated at 0.83 for males and females CC has shown the same accuracy and precision as the EKFC_Creat. Please note that the above Q_CC is not available for Black US populations.

The EKFC_CC equations (that are also used in the calculator above) are:

eGFR by EKFC_cr-cys

Additionally, an EKFC equation combining cystatin C and serum creatinine (mean value of EKFC_Creat and EKFC_CC, noted as: EKFC eGFRcr-cys) demonstrated significantly better performance to estimate GFR. 90% of the estimated glomerular filtration rate were within ±30% of the measured GFR.

The EKFC eGFRcr-cys equation also had better accuracy in estimating the GFR than the recommended CKD-EPI equations and other full age range cystatin C equations, including the full-age-spectrum and CAPA equations.

eGFR EKFC Equation Calculator Functionality Explained

The above calculator was built with the aim to efficiently compile the latest EKFC equation and serum creatinine and/or cystatin C scaling values in an easy to use tool, to facilitate the clinical use of this GFR estimation method, devised in years of research and numerous studies by the European Kidney Function Consortium.

The variables required consist in:

• Patient Age: Applicable for 2 – 90 years old
• Sex: Female/Male
• Population: This is a variable that is only activated if patient age is between 18 – 90 years old and includes the choices of White Europeans, Black Europeans, White US, Black US, Black Africans and Not known.
• Serum Creatinine: expressed in mg/dL, with an option to input a µmol/L value which will then be converted to mg/dL (1 µmol/L = 0.0113 mg/dL)
• Serum Cystatin C: expressed in mg/L

Depending on the variables selected and inputted, the calculator may provide 3 eGFR values, all expressed in mL/min/1.73m²:

• eGFR EKFC_Creat
• eGFR EKFC_CC
• eGFR EKFC_cr-cys

The table below summarizes the specific equations and Q values used by the calculator to determine each of the 3 estimates:

References

Pottel H, Delanaye P, Schaeffner E, Dubourg L, Eriksen BO, Melsom T, Lamb EJ, Rule AD, Turner ST, Glassock RJ, De Souza V, Selistre L, Goffin K, Pauwels S, Mariat C, Flamant M, Ebert N. Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin C. Nephrol Dial Transplant. 2017; 32(3):497-507.

Pottel H, Delanaye P. Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate. Ann Intern Med. 2021;174(7):1038.

Pottel H, Björk J, Rule AD, Ebert N, Eriksen BO, Dubourg L, Vidal-Petiot E, Grubb A, Hansson M, Lamb EJ, Littmann K, Mariat C, Melsom T, Schaeffner E, Sundin PO, Åkesson A, Larsson A, Cavalier E, Bukabau JB, Sumaili EK, Yayo E, Monnet D, Flamant M, Nyman U, Delanaye P. Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex. N Engl J Med. 2023; 388(4):333-343.

Delanaye P, Cavalier E, Pottel H, Stehlé T. New and old GFR equations: a European perspective. Clin Kidney J. 2023; 16(9):1375-1383.

Pottel H, Delanaye P, Cavalier E. Exploring Renal Function Assessment: Creatinine, Cystatin C, and Estimated Glomerular Filtration Rate Focused on the European Kidney Function Consortium Equation. Ann Lab Med. 2024; 44(2):135-143.

Delanaye P, Vidal-Petiot E, Björk J, Ebert N, Eriksen BO, Dubourg L, Grubb A, Hansson M, Littmann K, Mariat C, Melsom T, Schaeffner E, Sundin PO, Bökenkamp A, Berg UB, Åsling-Monemi K, Åkesson A, Larsson A, Cavalier E, Dalton RN, Courbebaisse M, Couzi L, Gaillard F, Garrouste C, Jacquemont L, Kamar N, Legendre C, Rostaing L, Stehlé T, Haymann JP, Selistre LDS, Strogoff-de-Matos JP, Bukabau JB, Sumaili EK, Yayo E, Monnet D, Nyman U, Pottel H, Flamant M. Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil and Africa. Nephrol Dial Transplant. 2023; 38(1):106-118.

Delanaye P, Rule AD, Schaeffner E, Cavalier E, Shi J, Hoofnagle AN, Nyman U, Björk J, Pottel H. Performance of the European Kidney Function Consortium (EKFC) creatinine-based equation in United States cohorts. Kidney Int. 2024; 105(3):629-637.