Recommendations for Implementing the CKD-EPI 2021 Race-Free eGFR Calculation: Guidelines for Clinical Laboratories

Table of Contents

When introducing the new eGFR equations for eGFRcr and eGFRcr-cys and the testing is not reported by the laboratory

This text can be used or modified to meet the needs of the laboratory, health care professionals and patients.

Effective <DATE>, our laboratory is changing the calculation of estimated glomerular filtration rate (eGFR) from creatinine to the new CKD-EPI 2021 equation that does not include a race coefficient.  The new equation is recommended by the National Kidney Foundation and the American Society of Nephrology’s Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. The new eGFRcr equation has similar overall performance characteristics to the older equations and has been assessed to not have potential consequences that disproportionately affect any one group of individuals. For most patients the eGFRcr result will be similar, however, for some, the values may differ by more than 10% particularly at higher values of eGFRcr and for younger adult ages. Please go to eGFR Calculator | National Kidney Foundation to compare the new CKD-EPI 2021 eGFRcr result with a previously calculated eGFR based on older equations.

The eGFRcr values using the new equation will only report one value and will use nomenclature to distinguish results from the older equations. Results will not trend with those using the older equations. The new report name is eGFRcr (calculated using only creatinine)

<INCLUDE THE NEXT SENTENCE IF APPLICABLE FOR A LABORATORY.> We are also introducing the Kidney Profile order that includes both creatinine with calculated eGFRcr and urine albumin-creatinine ratio (uACR). Clinical practice recommendations suggest ordering uACR with serum creatinine to facilitate appropriate classification of patients with chronic kidney disease, to assess risk for progression and to monitor patients at risk to develop CKD.  

When evaluating a patient’s GFR, it is important to remember that eGFR is an estimate of the patient’s GFR. For eGFRcr and eGFRcys (calculated from cystatin C), 80-90% of values are within 30% of measured GFR. eGFRcr-cys (calculated using both creatinine and cystatin C) is more accurate than either eGFRcr or eGFRcys alone.

eGFRcr values need to be interpreted based on clinical context. Clinical practice recommendations suggest ordering cystatin C as a confirmatory test for patients with eGFRcr of 45-59 mL/min/1.73m2 with uACR <30 mg/g, and in patients for whom the creatinine may be a less reliable indicator of GFR near decision points. eGFRcr-cys provides a more accurate estimate of GFR. In addition, eGFRcys may be more accurate in conditions when creatinine is a less reliable test for estimating the GFR. Situations in which non-GFR factors may have a large affect on serum creatinine include alterations in creatinine generation (muscle wasting diseases, amputees, body builders, vegan diet), drugs that affect tubular secretion of creatinine (cimetidine, cobicistat, dolutegravir, fenofibrate, ritonovir, trimethoprim and others), and conditions with extra-renal elimination of creatinine (gastrointestinal and “third-space” losses).  Clinicians must also consider non-GFR factors affecting cystatin C, including smoking, obesity, inflammation and disorders of thyroid or adrenal hormones.

References

Delgado C, Baweja M, Crews DC, et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. Am J Kidney Dis. 2021 DOI: 10.1053/j.ajkd.2021.08.003

Inker LA, Eneanya ND, MCorsh J, et al. New Creatinine- and Cystatin C–Based Equations to Estimate GFR without Race. New England J Med. 2021: DOI: 10.1056/NEJMoa2102953

When introducing the new eGFR equations for eGFRcr and for eGFRcr-cys

This text can be used or modified to meet the needs of the laboratory, health care professionals and patient.

Effective <DATE>, our laboratory is changing the calculation of estimated glomerular filtration rate (eGFR) from creatinine and from combined creatinine-cystatin C to the new CKD-EPI 2021 equations that do not include a race coefficient.  The new equations are recommended by the National Kidney Foundation and the American Society of Nephrology’s Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. The new eGFRcr equation has similar overall performance characteristics to the older equations and has been assessed to not have potential consequences that disproportionately affect any one group of individuals. For most patients the eGFRcr result will be similar, however, for some, the values may differ by more than 10% particularly at higher values of eGFRcr and for younger adult ages. Please go to eGFR Calculator | National Kidney Foundation to compare the new CKD-EPI 2021 eGFRcr result with a previously calculated eGFR based on older equations.

The eGFR values using the new equations will only report one value and will use nomenclature to distinguish results from the older equations. Results will not trend with those using the older equations. The new report names are:

  • eGFRcr (calculated using only creatinine)
  • eGFRcr-cys (calculated using both creatinine and cystatin C)
  • eGFRcys (calculated using only cystatin C)

<INCLUDE THE NEXT SENTENCE IF APPLICABLE FOR A LABORATORY.> We are also introducing the Kidney Profile order that includes both creatinine with calculated eGFRcr and urine albumin-creatinine ratio (uACR). Clinical practice recommendations suggest ordering uACR with serum creatinine to facilitate appropriate classification of patients with chronic kidney disease, to assess risk for progression and to monitor patients at risk to develop CKD.  

When evaluating a patient’s GFR, it is important to remember that eGFR is an estimate of the patient’s GFR. For eGFRcr and eGFRcys, 80-90% of values are within 30% of measured GFR. eGFRcr-cys is more accurate than either eGFRcr or eGFRcys alone.

eGFRcr values need to be interpreted based on clinical context. Clinical practice recommendations suggest ordering cystatin C as a confirmatory test for patients with eGFRcr of 45-59 mL/min/1.73m2 with uACR <30 mg/g, and in patients for whom the creatinine may be a less reliable indicator of GFR near decision points. eGFRcr-cys provides a more accurate estimate of GFR. In addition, eGFRcys may be more accurate in conditions when creatinine is a less reliable test for estimating the GFR. Situations in which non-GFR factors may have a large affect on serum creatinine include alterations in creatinine generation (muscle wasting diseases, amputees, body builders, vegan diet), drugs that affect tubular secretion of creatinine (cimetidine, cobicistat, dolutegravir, fenofibrate, ritonovir, trimethoprim and others), and conditions with extra-renal elimination of creatinine (gastrointestinal and “third-space” losses).  Clinicians must also consider non-GFR factors affecting cystatin C, including smoking, obesity, inflammation and disorders of thyroid or adrenal hormones.

References

Delgado C, Baweja M, Crews DC, et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. Am J Kidney Dis. 2021 DOI: 10.1053/j.ajkd.2021.08.003

Inker LA, Eneanya ND, MCorsh J, et al. New Creatinine- and Cystatin C–Based Equations to Estimate GFR without Race. New England J Med. 2021: DOI: 10.1056/NEJMoa2102953

Suggested laboratory report comment messages

CircumstanceMessage
Laboratory report, prior to change (with implementation date not determined)Reported eGFR is based the [ADD CURRENT] equation. The laboratory is working to implement the new CKD-EPI 2021 equation that does not use a race coefficient. In the interim, to calculate eGFR based on the CKD-EPI 2021 equation, go to CKD-EPI Creatinine Equation (2021) | National Kidney Foundation.
Laboratory report, prior to change (perhaps one month prior to change)Reported eGFR is based the [ADD CURRENT] equation. Effective DATE, the laboratory will implement the new CKD-EPI 2021 equation. In the interim, to calculate eGFR based on the CKD-EPI:2021 equation, go to CKD-EPI Creatinine Equation (2021) | National Kidney Foundation.
Laboratory report, after implementing the changeReported eGFR is based the CKD-EPI 2021 equation that does not use a race coefficient.
Laboratory report reported eGFR of 45-59 mL/min/1.73m2. Laboratories need to identify a referral laboratory or offer eGFRcr-cys  prior to listing this commentNKF KDOQI and KDIGO guidelines recommend confirming eGFR of 45-59 mL/min/1.73m2 with uACR <30 mg/g based on eGFR calculated using both creatinine and cystatin C.

Table S1: Values to verify appropriate calculation of eGFRcr

AGE (years)Sex Serum Creatinine
mg/dL		 eGFRcr
(CKD-EPI 2021)
mL/min/1.73m2
<18Male do not calculate
<18Female do not calculate
18Male0.90127
18Male0.91125
18Female0.70128
18Female0.71126
90Male0.5097
90Male1.5044
90Female0.5089
90Female1.5033
not available  do not calculate
 not available do not calculate
Creatinine below or above the measuring interval
(analytical measurement range)		 do not calculate
(see notes)

NOTES

The creatinine values for age 18 years will confirm the correct equation is used at the splice or knot value in the equations. The creatinine values at other ages recheck the calculation both below and above the splice or knot value in the equations.

Table S1 is based on non-SI units (mg/dL). To convert serum creatinine values to SI units (μmol/L) multiply by 88.4.

When creatinine is below or above the measuring interval (analytical measurement range), a laboratory may choose to report eGFRcr as less than or greater than the eGFRcr value that is calculated for concentrations at the respective limits of the measuring interval.

Table S2: Values to verify appropriate calculation of eGFRcr-cys

AGE (years)Sex Serum Creatinine
mg/dL		 Serum Cystatin C
mg/L		 eGFRcr-cys
(CKD-EPI:2021)
mL/min/1.73m2
<18Male  do not calculate
<18Female  do not calculate
18Male0.900.80126
18Male0.900.81125
18Female0.700.80121
18Female0.700.81120
18Male0.910.80125
18Male0.910.81124
18Female0.710.80120
18Female0.710.81119
30Male1.500.8091
30Male1.500.8190
30Female1.500.8076
30Female1.600.8173
not available   do not calculate
 not available  do not calculate
Creatinine below or above the measuring interval
(analytical measurement range)		do not calculate
(see notes)

NOTES

The creatinine values for age 18 years will confirm the correct equation is used at the splice or knot value in the equations.  The creatinine values at other ages recheck the calculation both below and above the splice or knot value in the equations.

Table S2 is based on non-SI units (mg/dL). To convert serum creatinine values to SI units (μmol/L) multiply by 88.4.

When creatinine and/or cystatin C is below or above the measuring interval (analytical measurement range), a laboratory may choose to report eGFRcr-cys as less than or greater than the eGFRcr-cys value that is calculated for concentrations at the respective limits of the measuring intervals.

Table S3. Equations to calculate eGFRcr with creatinine in SI units

Logica 
AgeSexSCrb (µmol/L)eGFR Equation
>=18Female<=61.9= 142 x (Scr /61.88)-0.241 x 0.9938Age x 1.012
>61.9= 142 x (Scr /61.88)-1.200 x 0.9938Age x 1.012
Male<=79.6= 142 x (Scr /79.56)-0.302 x 0.9938Age
>79.6= 142 x (Scr /79.56)-1.200 x 0.9938Age

a Programming logic for “If” statements to select the correct equation for each set of parameters.

a Scr = serum creatinine in µmol/L

Table S4. Equations to calculate eGFRcr-cys with creatinine in SI units

Logica 
AgeSexSCrb (µmol/L)SCys (mg/L)eGFRCr-Cys
>=18Female≤61.9≤0.80135 x (Scr/61.88)-0.219 x (Scys/0.8)-0.323 x 0.9961Age x 0.963
>0.80135 x (Scr/61.88)-0.219 x (Scys/0.8)-0.778 x 0.9961Age x 0.963
>61.9≤0.80135 x (Scr/61.88)-0.544 x (Scys/0.8)-0.323 x 0.9961Age x 0.963
>0.80135 x (Scr/61.88)-0.544 x (Scys/0.8)-0.778 x 0.9961Age x 0.963
Male≤79.6≤0.80135 x (Scr/79.56)-0.144 x (Scys/0.8)-0.323 x 0.9961Age
>0.80135 x (Scr/79.56)-0.144 x (Scys/0.8)-0.778 x 0.9961Age
>79.6≤0.80135 x (Scr/79.56)-0.544 x (Scys/0.8)-0.323 x 0.9961Age
>0.80135 x (Scr/79.56)-0.544 x (Scys/0.8)-0.778 x 0.9961Age

a Programming logic for “If” statements to select the correct equation for each set of parameters.

b Scr = serum creatinine in µmol/L

Programming the eGFR cystatin C equation

From reference 14, the equation for ages <=18 years in a single expression for eGFRcys is:

eGFRcys = 133 x min(Scys/0.8, 1)-0.499 x max(Scys/0.8, 1)-1.328 x 0.996Age x 0.932 [if female]

where             Scys = serum cystatin C in mg/L

Age (years)

 

The coding for implementing the single equation is nuanced.  The “min(Scys/0.8, 1)” factor indicates the minimum of Scys/0.8 or 1.0 and “max(Scys/0.8, 1)” indicates the maximum of Scys/0.8 or 1.0. 

Coding may be simpler if the single equation is expressed as four equations applicable to four logical conditions as in Table S5.

Table S5. Equations to calculate eGFRcys

Logica 
AgeSexSCysb (mg/L)eGFR Equation
>=18Female<=0.8= 133 x (Scys/0.8)-0.499 x 0.996Age x 0.932
>0.8= 133 x (Scys/0.8)-1.328 x 0.996Age x 0.932
Male<=0.8= 133 x (Scys/0.8)-0.499 x 0.996Age
>0.8= 133 x (Scys/0.8)-1.328 x 0.996Age

a Programming logic for “If” statements to select the correct equation for each set of parameters.

b Scys = serum cystatin C