Glomerular Filtration Rate (GFR)

Chronic kidney disease is a worldwide problem that carries a substantial risk for cardiovascular morbidity and death.  Current guidelines define chronic kidney disease as kidney damage or glomerular filtration rate (GFR) less than 60 mL/min per 1.73 m2 for three months or more, regardless of cause.  The assay of creatinine in serum or plasma is the most commonly used test to assess renal function.

Creatinine is a break-down product of creatine phosphate in muscle and is usually produced at a fairly constant rate by the body (depending on muscle mass). It is freely filtered by the glomeruli and, under normal conditions, is not re-absorbed by the tubules to any appreciable extent. A small but significant amount is also actively secreted. Since a rise in blood creatinine is observed only with marked damage of the nephrons, it is not suited to detect early stage kidney disease.

A considerably more sensitive test and better estimation of glomerular filtration rate (GFR) is given by the creatinine clearance test based on creatinine concentration in urine and serum/plasma, and urine flow rate.  For this test a precisely timed urine collection (usually 24 hours) and a blood sample are needed.  However, since this test is prone to error due to the inconvenient collection of timed urine, mathematical attempts to estimate GFR based only on the creatinine concentration in serum or plasma have been made.

GFR estimates using creatinine have often included a race component (e.g., African-American vs. non-African-American). However, formulation of equations that do not use race have more recently gained favor and have been recommended by multiple professional societies and task forces.

On August 16, 2022, the University of Iowa Hospitals and Clinics (UIHC) switched to the 2021 CKD-EPI creatinine refit without the race variable equation for adult patients 18 years and older:

eGFR = 142 X min(Scr/k,1)α X max(Scr/k, 1)-1.200 0.9938age X 1.012 [if female]

where Scr is serum creatinine, k is 0.7 for females or 0.9 for males, α is -0.241 for females and -0.302 for males, min indicates the minimum of Scr/k or 1, max indicates the maximum of Scr/k or 1.

On August 16, 2022, UIHC also introduced two eGFR calculations based on cystatin C. The first uses the 2012 cystatin C-based CKD-EPI equation which does not contain any race-based variables. This calculation is performed for all serum/plasma cystatin C orders. This will be resulted as a separate eGFR component below the cystatin C value in Epic as "eGFRcys (CKD-EPI 2012)".

The 2012 cystatin C-based CKD-EPI equation is:

eGFR = 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].

The second cystatin C-based equation combines both creatinine and cystatin C. This uses the 2021 eGFRcr-cys(CKD-EPI) refit without race variable equation. This calculation is performed for all serum/plasma specimens for which both creatinine and cystatin C are ordered. This is resulted as a separate eGFR component below the cystatin C value in Epic as "eGFRcys-cr (CKD-EPI 2021)".

The 2021 eGFRcr-cys(CKD-EPI) refit without race variable equation is:

eGFR = 135 X min(Scr/k,1)α X max(Scr/k,1)-0.544 X min(Scys/0.8,1)-0.323 X max(Scys/0.8,1)-0.778 X 0.9961age X 0.963 [if female]

where Scr is serum creatinine Scys is serum cystatin C, k is 0.7 for females and 0.9 males, α is -0.219 for females and -0.144 for males, min indicates the minimum of Scr/k or 1, max indicates the maximum of Scr/k or 1.

Cystatin C-based equations represent an alternative to eGFR equations based on creatinine alone and may offer advantages in some clinical situations (e.g., spinal cord injury with skeletal muscle loss) that may impact creatinine-based equations.

In children, there is not a single formula recommended for all ages. However, the Schwartz formula is frequently used and appropriate for most ages, but should be used with caution or avoided in premature infants in the first several months of life. In the premature infant population, more specialized equations are often used. The pediatric Schwartz equation is

GFR (mL/min/1.73 m2) = (0.41 x Height) / Scr
were Scr is serum/plasma creatinine in mg/dL

Additional resources:
1. National Kidney Foundation

2. National Kidney Disease Education Program (NKDEP)

3. National Kidney Foundation eGFR Calculator

4. Delgado C 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. 2022 Feb;79(2):268-288.e1. doi: 10.1053/j.ajkd.2021.08.003.