Creatinine clearance

D. W. Cockcroft and M. H. Gault developed the Cockcroft-Gault method named after them in 1976 for estimating creatinine clearance (Cockcroft 1974). The method, also known as the "CG formula", is still used today to determine the dosage of medication in cases of known renal insufficiency (Geberth 2014).

The MDRD formula for estimating the GFR was developed at the end of the 1990s and was used for a long time (Geberth 2014).

In 2013, a group of researchers from the NIDDKD and the CKD-EPI developed the CKD-EPI formula, which provides a better estimate of the GFR (Geberth 2014).

Creatinine clearance is the plasma volume that can be cleared of creatinine within a certain unit of time through urine formation (Herold 2025).

Indication

Creatinine clearance is determined for:

• Checking renal function
• Monitoring the progress of impaired kidney function
• Checking kidney function after prolonged treatment with drugs that damage the kidneys (Schaenzler 2016)

Standard values:

The standard values for creatinine clearance up to the age of 30 are:

• Women: 71-121 ml/min
• Men: 74-120 ml/min.

After the age of 30, the values fall by approx. 10 ml/min. per decade of life (Schaenzler 2016)

Increased creatinine clearance value:

• In the early stages of diabetes mellitus
• At the beginning of pregnancy (Schaenzler 2016)

Decreased creatinine clearance value:

• Acute or chronic kidney failure
• Long-term therapy with nephrotoxic substances such as cimetidine, gentamicin, indomethacin, various diuretics (Schaenzler 2016)

Creatinine clearance indicates pathological values at a very early stage, i.e. when serum creatinine is still within the normal range.

It can be determined in two different ways, firstly by calculation and secondly by estimation (Herold 2025)

I. Procedure by calculation:

The patient collects his 24-hour urine for this purpose. The creatinine concentration in the serum and in the 24-hour urine is determined and then the creatinine clearance is calculated using the following formula:

• C (ml/min) = UxUV / Sxt

U= creatinine concentration in urine

UV= urine volume within 24 h

S= Creatinine concentration in serum

T= Collection time in minutes (24x60= 1440)

(Herold 2025)

Disadvantage:

This method not only requires good patient instruction, but also involves numerous potential sources of error. In addition, this method overestimates the GFR, as creatinine is not only exclusively filtered glomerularly (80% [Guder 2017]), but is also secreted tubularly to a lesser extent (20% [Guder 2017]). For this reason, this method is now rarely used in practice (Herold 2025).

II Procedure by estimation:

When estimating creatinine clearance, the GFR is estimated using various equations. These equations are based on simultaneous determination of serum creatinine and cystatin C (Herold 2025).

• The KDIGO guidelines:

The creatinine-based CKD-EPI eGFRcr and cystatin C-based CKD-EPI eGFRcys equations are recommended according to the KDIGO guidelines. In 2021, however, the CKD-EPI research group developed a new CKD-EPI eGFRcr formula that has a gender-specific variable but is independent of age and skin color (Herold 2025).

It should be noted that the glomerular filtrate shows a physiological decrease with increasing age (Herold 2025).

• EKFC estimation formula:

Developed by the European Kidney Function Consortium (EKFC), this formula consists of a creatinine-based estimation formula that can be used to determine GF independent of gender and skin color using rescaled serum creatinine values (Herold 2025).

• Cockcroft-Gault estimation:

This method takes into account age as well as gender, body weight and serum creatinine. However, this formula has now been largely replaced by the MDRD formula or others, as it has since become known that creatinine is also secreted and is therefore measured too high in plasma. The formula is:

Clearance (ml/min) = 140 - age in years x body weight in kg/ 72 x creatinine in plasma/serum (mg/dl). For women, the result is multiplied by 0.85 (Guder 2017).

• MDRD formula:

This formula is considered a cost-effective variant. The formula was developed at the end of the 1990s. It is also recommended by the European Guidelines. The disadvantage is that this formula cannot be used for patients with normal kidney function or slightly impaired kidney function, as the GFR above 60 ml/min is overestimated by approx. 10 ml/min (Geberth 2011).

• CKD-EPI:

The CKD-EPI formula is the most commonly used formula today, as it is more accurate than the MDRD formula for borderline renal function 8ab approx. > 60 ml/min/1.73m2). It has also been validated for older people (Schwenger 2024).

Creatinine is a breakdown product of muscle metabolism, but creatinine is also absorbed through food. As it is excreted almost entirely via the kidneys, it is used as a parameter for monitoring kidney function. Creatinine can be determined in blood serum as well as in blood plasma and in collected urine (Schaenzler 2016).

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