Clinical Information

In muscle metabolism, creatinine is synthesized endogenously from creatine and creatine phosphate. Creatinine is removed from plasma by glomerular filtration into the urine without being reabsorbed by the tubules to any significant extent. Renal tubular secretion also contributes a small quantity of creatinine to the urine. As a result, creatinine clearance often overestimates the true glomerular filtration rate (GFR) by 10% to more than 20%.

Determinations of creatinine and renal clearance of creatinine are of value in the assessment of kidney function. Serum or blood creatinine levels in kidney disease generally do not increase until kidney function is substantially impaired.

Estimated GFR (eGFR) is calculated using the 2021 Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) Cr equation:

eGFR =142 x min(standardized Scr/K,1)alpha x max(Scr/K, 1)-1.200 x 0.9938age x 1.012(if patient is female)

-where age is in years

-Scr is serum creatinine

-k is 0.7 for females and 0.9 for males

-alpha 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

Use of an estimating or prediction equation to estimate GFR from serum creatinine should be employed for people with CKD and those with risk factors for CKD (diabetes, hypertension, cardiovascular disease, and family history of kidney disease). Reasons given for routine reporting of eGFR with every serum creatinine in adult (18 and over) patients include:

-GFR and creatinine clearance are poorly inferred from serum creatinine alone. GFR and creatinine clearance are inversely and nonlinearly related to serum creatinine. The effects of age and sex further cloud interpretation.

-Creatinine is commonly measured in routine clinical practice. Albuminuria (>30 mg/24 hour or urine albumin to creatinine ratio >30 mg/g) may be a more sensitive marker of early kidney disease, especially among patients with diabetic nephropathy. However, there is poor adherence to guidelines that suggest annual urinary albumin testing of patients with known diabetes. Therefore, if a depressed eGFR is calculated from a serum creatinine measurement, it may help providers recognize early CKD and pursue appropriate follow-up testing and therapeutic intervention.

-Monitoring of kidney function (by GFR or creatinine clearance) is essential once albuminuria is discovered. Estimated GFR is a more practical means to closely follow changes in GFR over time, when compared to direct measurement using methods such as iothalamate clearance.

-The CKD-EPI equation does not require weight or height variables. From a serum creatinine measurement, it generates a GFR result normalized to a standard body surface area (1.73 m[2]) using sex and age. Unlike the Cockcroft-Gault equation, height and weight, which are often not available in the laboratory information system, are not required. The 2021 CKD-EPI Cr equation does not require race, so eGFR values for both African Americans and non-African Americans are no longer reported. The new 2021 CKD-EPI eGFR values cannot be directly compared to the previous 2009 CKD-EPI Cr eGFR values that were separately reported for African American and non-African American populations.

The Kidney Disease: Improving Global Outcomes (KDIGO) CKD work group clinical practice guideline,(2) as further defined by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) commentary,(3) provide the following recommendations for reporting and interpretation of serum creatinine and eGFR, which were revised after development of a refit CKD-EPI Creatinine eGFR equation in 2021 that does not require a mathematical adjustment based on race:

-1.4.3: Evaluation of GFR

-1.4.3.1: We recommend using serum creatinine and a GFR estimating equation for initial assessment. (1A)

1.4.3.2: We suggest using additional tests (such as cystatin C or a clearance measurement) for confirmatory testing in specific circumstances when eGFR based on serum creatinine is less accurate. (2B)

1.4.3.3: We recommend that clinicians (1B):

-Use a GFR estimating equation to derive GFR from serum creatinine (eGFRcreat) rather than relying on the serum creatinine concentration alone.

-Understand clinical settings in which eGFRcreat is less accurate.

1.4.3.4: We recommend that clinical laboratories should (1B):

-Measure serum creatinine using a specific assay with calibration traceable to the international standard reference materials and minimal bias compared to isotope-dilution mass spectrometry (IDMS) reference methodology.

-Report eGFRcreat in addition to the serum creatinine concentration in adults and specify the equation used whenever reporting eGFRcreat.

-Report eGFRcreat in adults using the 2021 CKD-EPI creatinine equation.

When reporting serum creatinine:

-We recommend that serum creatinine concentration be reported and rounded to the nearest whole number when expressed as standard international units (mmol/l) and rounded to the nearest 100th of a whole number when expressed as conventional units (mg/dL).

When reporting eGFRcreat:

-We recommend that eGFRcreat should be reported and rounded to the nearest whole number and relative to a body surface area of 1.73 m2 in adults using the units mL/min/1.73 m2.

-We recommend eGFRcreat levels less than 60 mL/min/1.73 m2 should be reported as "decreased."

1.4.3.8: We suggest measuring GFR using an exogenous filtration marker under circumstances where more accurate ascertainment of GFR will impact treatment decisions (2B)