CKD, eGFR and Cockcroft-Gault

Chronic kidney disease (CKD) is a major public health problem in Australia and throughout the world. It is estimated that 10% of all adults presenting to a general practitioner in Australia have CKD while 80% have at least one risk factor for CKD.

This article discusses how the estimated glomerular filtration rate (eGFR) automatically reported with biochemical tests is used as an assessment tool for CKD, why creatinine clearance calculated with the Cockcroft-Gault equation is the recommended estimate of GFR for use in drug dose calculations, and the limitations of Cockcroft-Gault to be considered.

CKD is often present in the context of cardiovascular disease or diabetes but early CKD is often asymptomatic. The clinician must therefore recognise and apply the active approach required to detect CKD in high risk patients including: those who are overweight or obese, have hypertension, have a familial history of CKD, are a smoker, or are of Aboriginal or Torres Straight Islander decent and 30 years of age or older.

Several tests are used for the detection of CKD including albuminuria, albumin: creatinine ratio, haematuria, blood pressure and serum creatinine. Serum creatinine used alone as a measure of renal function is unreliable and insensitive. However serum creatinine can be used to derive a value for creatinine clearance and an estimation of GFR and renal function.

Most Australian pathology laboratories now routinely report an estimated GFR in all biochemical test results that include serum creatinine. This eGFR value is derived using the CKD-EPI formula. CKD-EPI refers to the CKD-Epidemiology Collaboration Equation. This equation does not require the patient’s actual or ideal body weight to be known.

This reported eGFR can be used as a screening tool for the early detection of CKD. An eGFR of <60mL/min/1.73m² that is present for three months or more with or without other evidence of kidney damage (such as proteinuria), is diagnostic for CKD. An eGFR of <60mL/min/1.73m² is associated with increased risk of adverse renal, cardiovascular and other clinical outcomes, irrespective of age.

While the eGFR reported with all serum creatinine test results for those aged 18 years of age or over is a tool for CKD screening, it is not recommended for routine use in calculating dose reductions required for patients with CKD.

The Australia Medicines Handbook (AMH) recommends that such reported eGFR values are not equivalent to CrCl (creatinine clearance) and should not be used for estimating drug dose reductions in renal impairment. This remains in line with most manufacturer’s dose reduction recommendations, which are largely based on data calculated using the Cockcroft-Gault equation and not eGFR values.

The Cockcroft-Gault equation (Figure 1) remains the most widely recognised equation for the calculation of creatinine clearance and its estimation of GFR.

Figure 1. Cockcroft-Gault Equation.

When using Cockcroft-Gault to estimate GFR for the purpose of dose reduction recommendations, it is important to remember the limitations of the equation and that certain clinical settings require careful interpretation of the result.

Serum creatinine, and thus the calculated estimate of GFR, can be influenced by many factors. These include:

• Patients on high protein diets, creatine or amino acid supplementation
• Extremes of age
• Extremes of weight
• Diseases or conditions affecting skeletal muscle mass
  (consider paraplegia, amputation, high muscle mass individuals)
• Dialysis
• Acutely changing renal function, and
• Populations where the equation is not validated
  (consider children, Aboriginal or Torres Strait Islander)

It is important to note that in overweight and obese patients, the ideal body weight must be used in the Cockcroft-Gault equation as using the patient’s actual weight will overestimate renal function and lead to possible overdosing.

In summary, it is important to note that the eGFR reported with biochemical test results is an important indicator and screening tool for the early detection and diagnosis of CKD. It provides an instrument for better risk management in CKD with the aim of optimal disease management and best health outcomes.

The use of the Cockcroft-Gault equation to calculate CrCl and estimate GFR is relatively simple and reliable, provided that the limitations are considered when using the calculated data. This calculation remains the most widely used and recognised for dose reduction considerations.