Glomerular Filtration Rate (GFR)

Measured Glomerular Filtration Rate (GFR) is the most accurate measure of kidney function. It uses the clearance of an external filtration marker during a 24-hour urine collection.

This is time-consuming and difficult to do in practice.

Estimated Creatinine Clearance (CrCl)

The alternative to directly measuring GFR is estimating Creatinine Clearance (CrCl) using a single blood level of creatinine and a mathematical formula. The single creatinine level must be at steady state (stable from day to day), to provide an accurate estimate of kidney function.

Using serum creatinine to estimate kidney function has limitations. For example, serum creatinine levels are dependent on muscle mass, diet, hydration, and are not accurate in acute kidney injury (AKI).

There are various formulas, and they consider different variables to estimate kidney function, such as age, race, sex and weight.

Cockcroft and Gault formula

The MHRA outlines circumstances where the Cockcroft-Gault (CG) formula should be used to calculate (CrCl) to guide drug dosing. For example, direct-acting oral anticoagulants (DOACs) in adults. CG calculated CrCl is preferred to estimate GFR (eGFR) in these circumstances as eGFR may overestimate renal function. However, CG calculated CrCl is still only an estimate of actual GFR. The decision to implement changes to drug doses or monitoring should consider the full clinical picture and limitations of the formula.

The UK Renal Pharmacy Group provides information on the limitations of the Cockcroft and Gault formula.

Weight for calculation

Controversy exists over which weight to use in the CG formula as the calculation becomes less accurate at extremes of weight.

For, example in extremely overweight patients, actual body weight may overestimate renal function, possibly leading to excessive dosing. Conversely, in frail patients, use of actual body weight may underestimate renal function, possibly leading to subtherapeutic dosing.

The MHRA advises use of an application such as MDCALC Creatinine Clearance Calculator, which if the patient’s height is added, provides a range of CrCl results calculated using adjusted, ideal and actual body weight.

Where results cross or are close to a CrCl level that may require a dose change, follow local guidance where this exists. Alternatively, consider the full clinical picture including, but not limited to:

• estimated kidney function range
• trend in renal function
• the individual’s body composition
• consequences of under or overdosing

Estimated GFR (eGFR) formulas

The BNF and UK Renal Pharmacy Group recommend the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula for calculating eGFR. However, some laboratories may still report eGFR using the Modification of Diet in Renal Disease (MDRD) formula.

Do not use blood cystatin C levels instead of creatinine for estimating Glomerular Filtration Rate (eGFR).

Using both CrCl and eGFR calculation

It may be useful to calculate both CrCl and eGFR in the situations described below.

Where the two values for estimated kidney function are different and result in two difference renal doses for a medicine, consider the clinical impact of the dose difference.

For example, using the Cockcroft and Gault formula for a 80-year-old man weighing 60kg with a plasma creatinine of 120micromol/L will give a calculated creatinine clearance of 37mL/min. Using the CKD-EPI formula, the eGFR is 53mL/min/1.73m².

Estimated GFR calculated using CKD-EPI or MDRD is normalised to a standard body surface area of 1.73m². If using eGFR to calculate drug doses in patients at extremes of body weight or for drugs with a narrow therapeutic index first correct eGFR to actual GFR using the equation:

•  Actual GFR = (eGFR x BSA/1.73)

Overestimates of eGFR

eGFR may appear better than it actually is in the following populations:

• the elderly
• those on a low protein diet
• amputees
• those with conditions leading to muscle wasting (e.g. myasthenia gravis, late-stage muscular dystrophy, spinal cord injury)

Underestimates of eGFR

eGFR may appear worse than it actually is in the following populations:

• high muscle mass (e.g. high-level sport or body builder)
• high protein diet (e.g. taking protein supplements)
• muscle breakdown (e.g. after heavy exercise, myositis, muscular dystrophy)

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