Proxy markers of kidney function

Glomerular filtration rate (GFR) is the best overall measure of kidney function.1 Direct measurements of GFR require timed urine collections which can be expensive, complex and difficult to perform in routine clinical practice, so it is more practical to use proxy markers.1 These proxy markers– estimated glomerular filtration rate (eGFR) and creatinine clearance – are also used to guide dosing of medicines.2

Proxy markers

Proxy marker Where to find it Pros
Cons
eGFR
Provided in laboratory test results
  • A valid estimate of GFR3
  • Widely available on laboratory reports3

Few studies have been conducted directly linking dosing according to eGFR with pharmacokinetics or clinical outcomes3

Creatinine clearance Prescribing software
  • Accumulated clinical experience is available using creatinine clearance to guide dosing3
  • Most manufacturers’ data recommend dose adjustment is guided by creatinine clearance, estimated by the Cockcroft–Gault formula3
Primary clinical outcome studies to support use of creatinine clearance for dosing of medicines are lacking3

The Cockcroft–Gault formula4

Creatinine clearance (mL/min) = (140 – age) × (weight in kg) / 0.815 x serum creatinine (micromol/L)
Use either actual or ideal weight, whichever is lower. For females multiply the overall result by 0.85.

The Australian Medicines Handbook creatinine clearance calculator is available online.

Serum creatinine

Measurement of serum creatinine alone is not a reliable indicator of kidney function and should not be used in isolation for the purpose of prescribing medicines safely.2

When is eGFR unreliable/misleading?2

  • Acute changes in kidney function (e.g. acute kidney failure)
  • People on dialysis
  • Exceptional dietary intake (e.g. vegetarian diet, high protein diet, recent consumption of cooked meat, creatine supplements)
  • Diseases of skeletal muscle, paraplegia, or amputees (may overestimate eGFR) or high muscle mass (may underestimate eGFR)
  • Children under the age of 18 years
  • Severe liver disease present
  • eGFR values above 90 mL/min/1.73 m2
  • Medicines interacting with creatinine excretion (e.g. fenofibrate, trimethoprim)
  • Extremes of body size

eGFR and extremes of body size2

The eGFR assumes a person is of average body size (body surface area of 1.73 m2) and in very large or small patients may lead to unreliable or misleading results. In these cases it is recommended to calculate an eGFR that is not normalised to 1.73 m2 body surface area (BSA):

Uncorrected eGFR = [(the result from the CKD-EPI) X BSA] / 1.73
References
  1. Stevens LA, Coresh J, Greene T, et al. Assessing Kidney Function — Measured and Estimated Glomerular Filtration Rate. N Engl J Med 2006;354:2473–83. [Online]
  2. Kidney Health Australia. Chronic kidney disease (CKD) management in general practice. 2nd edition. 2012. http://www.kidney.org.au//LinkClick.aspx?fileticket=vfDcA4sEUMs%3d&tabid=635&mid=1584 (accessed 30 May 2013).
  3. Johnson DW, Jones GR, Mathew TH, et al. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: new developments and revised recommendations. Med J Aust 2012;197:224–5.[PubMed]
  4. Australian medicines handbook 2013. Adelaide: Australian Medicines Handbook Pty Ltd, 2013.