Creatinine Clearance

The measurement of accurate renal function is vital for the routine care of patients. Determining the renal function status can predict kidney disease progression and prevent toxic drug levels in the body. The glomerular filtration rate (GFR) describes the flow rate of filtered fluid through the kidneys. The gold standard measurement of GFR involves the injection of inulin and its clearance by the kidneys. However, the use of inulin is invasive, time-consuming, and an expensive procedure. Alternatively, the biochemical marker creatinine found in serum and urine is commonly used in the estimation of GFR. Creatinine clearance (CrCl) is the volume of blood plasma cleared of creatinine per unit time. It is a rapid and cost-effective method for the measurement of renal function. Both CrCl and GFR can be measured using the comparative values of creatinine in blood and urine.

Glomerular Filtration Rate

The GFR in the measurement of volume filtered through the glomerular capillaries and into the Bowman’s capsule per unit of time. The filtration in the kidney is dependent on the difference in high and low blood pressure created by the afferent (input) and efferent (output) arterioles, respectively. The clearance rate for a given substance equals the GFR when it is neither secreted nor reabsorbed by the kidneys. For such a given substance, the urine concentration multiplied by the urine flow equals the mass of the substance excreted during urine collection. This mass divided by the plasma concentration is equivalent to the volume of plasma from which the mass was originally filtered. Below is the equation used to determine GFR, typically recorded in volume per time (e.g., mL/min):

GFR = [UrineX (mg/mL)] * urine flow (mL/min)/ [PlasmaX (mg/mL)], where X is a substance that is completely excreted.

GFR approximation using Creatinine Clearance

Creatinine is a breakdown product of dietary meat and creatine phosphate found in skeletal muscle. Its production in the body is dependent on muscle mass. The CrCl rate approximates the calculation of GFR since the glomerulus freely filters creatinine. However, it is also secreted by the peritubular capillaries, causing CrCl to overestimate the GFR by approximately 10% to 20%. Despite the marginal error, it is an accepted method for measuring GFR due to the ease of measurement of CrCl.

Cockcroft-Gault formula: Estimated creatinine clearance rate (eCCR)

Creatinine clearance can be estimated using serum creatinine levels. The Cockcroft-Gault (C-G) formula uses a patient’s weight (kg) and gender to predict CrCl (mg/dL). The resulting CrCl is multiplied by 0.85 if the patient is female to correct for the lower CrCl in females. The C-G formula is dependent on age as its main predictor for CrCl. Below is the formula:

eCCr = (140 – Age) x Mass (kg) x [0.85 if female] / 72 x [Serum Creatinine (mg/dL)]

Formulas used in the prediction of GFR

Formulas derived using variables that influence GFR can provide varying degrees of accuracy in estimating GFR. The widely used Modification of Diet in Renal Disease Study Group (MDRD) employs four variables, including serum creatinine, age, ethnicity, and albumin levels. A further complex version of MDRD includes blood urea nitrogen and serum albumin in its formula. However, since the MDRD formula does not adjust for body size, results of eGFR are given in units of ml^-1 min^-1 1.73m^-2, 1.73m^2 due to body surface area in an adult with a mass of 63kg and height of 1.7m.

Other formulas used for GFR calculations and their employed variables to estimate GFR include Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. The CKD-EPI formulas are in categories based on patients who are black females, black males, non-black females, and non-black males. The Mayo Quadratic formula was developed to better estimate GFR in patients who have preserved renal function. Estimation of GFR in children uses the Schwartz formula, which employs serum creatinine (mg/dL) and the child’s height (cm).

In current clinical practice, the use of creatinine derived from the KDIGO clinical practice guidelines recommends the CKD-EPI formula for the estimation of GFR.