Creatinine clearance
Determination of creatinine clearance for a patient allows estimation of a patient’s renal function, and specifically the glomerular filtration rate (GFR). A patient’s GFR is a direct measure of clearance by glomerular filtration (ClGF), a major contributor to renal clearance of drugs. As such, determining GFR in a patient with renal insufficiency allows appropriate adjustment of the dosing regimen for a drug that is cleared predominantly or entirely by the kidneys.
Creatinine is a breakdown product of creatine in skeletal muscle, and is generated and released into the plasma at a relatively constant rate. Creatinine distributes throughout total body water and is cleared almost entirely by glomerular filtration. A very small fraction of creatinine may be cleared by secretion, and it is not reabsorbed from the distal tubules. The clearance rate for creatinine is therefore very similar to the ClGF, and thus offers a good estimate of GFR.
Given the relatively constant rate at which creatinine is produced across most adults, a measurement of creatinine in the serum represents the equivalent of a steady state concentration (Css) that would be determined by the rate at which creatinine is cleared. A slower rate for creatinine clearance will result in a higher Css for creatinine. Consequently, determining the concentration of creatinine in the serum and comparing it with the Css that would be expected in an individual with normal renal function provides a ratio that then allows calculation of the creatinine clearance rate that would generate that ratio. This is the patient’s GFR.
There are several methods available for calculating GFR based on a measurement of serum creatinine. The example provided below uses the CKD-EPI (chronic kidney disease – epidemiology collaboration) approach. The terms in the equation correct for patient age, weight etc.
Example
The CKD-EPI equation (revised in 2021) is the recommended approach to estimating GFR. Details of the equation, shown below, were taken from the website of the National Kidney Foundation of the United States (https://www.kidney.org/content/ckd-epi-creatinine-equation-2021).
eGFRcr = 142 x min(Scr/κ, 1)α x max(Scr/κ, 1)-1.200 x 0.9938Age x 1.012 [if female]
where:
Age (years)
The estimated GFR (eGFR) for a male patient, 56 years old, with a serum creatinine measurement of 0.94 mg/dl, would be:
142 x min(0.94/0.9, 1)-0.302 x max(0.94/0.9, 1)-1.200 x 0.993856
142 x (1)-0.302 x (1.044)-1.200 x 0.993856
= 95.2 ml/min/1.73 m2
The estimated GFR (eGFR) for a female patient, 79 years old, with a serum creatinine measurement of 1.06 mg/dl, would be:
142 x min(1.06/0.7, 1)-0.241 x max(1.06/0.7, 1)-1.200 x 0.993879 x 1.012
142 x (1)-0.241 x (1.514)-1.200 x 0.993879 x 1.012
= 53.4 ml/min/1.73 m2
Clinical Context
In clinical practice, while eGFR is the preferred measure of estimating and following CKD patients, there are also other methods for quickly estimating GFR in patients with renal dysfunction for the purpose of adjusting doses of medications that are renally cleared. Patients regularly present to hospital with an acute kidney injury, and they may also require adjustments of medications. The equations used have been validated against diagnostic imaging measures to compare estimates versus measured GFRs in differing patient populations.
One of the most commonly used equations for estimating GFR in adults for the purpose of medication adjustments is the Cockroft-Gault equation, although this approach is no longer recommended for clinical use. For children less than 18 years of age, a common approach is through use of the Bedside Schwartz equation:
Clcr = K * (height (cm)/Scr (μmol/l))
K=36.5
It is important to note that results are typically presented as a normalised value in units of ml/min/1.73m2. Automated calculators are readily available in most drug dosing software packages and in electronic health records. Clinically, it is important to balance the acuity of the kidney dysfunction and the risk of excessive doses in a patient with dysfunctional renal medication processing and the risk of under-dosing.
