Prescribing in renal impairment

Drug considerations

Renal impairment renders some drugs ineffective (eg frusemide) or toxic (eg methotrexate) unless an appropriate dose adjustment is made. Generally, if more than half the drug is excreted unchanged, consider a dose reduction in patients with renal impairment. If an active or toxic metabolite is formed, then clearance of the metabolite may also have to be considered.

Patient considerations

Consider the degree of renal impairment. Renal function and muscle mass both decline with age, so elderly people may have apparently normal serum creatinine. When prescribing for the elderly, assume at least a mild degree of renal impairment (see also Prescribing for the elderly).

Check renal function before prescribing any drug that requires dose modification in renal impairment, even if only mild impairment is likely. In patients with severe and chronic renal disease, prescribing should be undertaken by nephrologists or other specialist clinicians.

Degree of impairment should be estimated using weight, age, gender and serum creatinine. The Cockcroft–Gault equation estimates creatinine clearance in millilitres per minute and has been validated for use in calculation of drug doses in adults with renal impairment.

Be aware that the estimate of glomerular filtration rate (eGFR) automatically reported with electrolyte test results is not equivalent to creatinine clearance and that there is no evidence that it is suitable for adjusting drug doses in people with renal impairment. For more detailed information, see www.australianprescriber.com/magazine/30/1/17/20/

Serum creatinine–creatinine clearance relationship

The formula below should not be used to estimate creatinine clearance in severe renal insufficiency, or with rapidly changing renal function.

After starting treatment monitor the patient closely for clinical and adverse effects. Drug concentrations should be measured when possible. The dose should be adjusted to provide optimal effects and drug concentration.

Estimate of creatinine clearance

Calculate from the formula of Cockcroft and Gault, 1976:

Calculator for this formula

Clcr mL/minute (males) =	(140 – age) x (weight in kg)
	0.815 x Secr(micromol/L)

where Cl_cr is creatinine clearance, Se_cr is serum creatinine and weight is ideal or actual weight, whichever is lower (see Ideal weight).

Females, multiply the estimated value by 0.85.

Ideal weight

Calculate from the following formulae:

Females 45.5 kg + 0.9 kg/cm for each cm >152 cm.

Males 50 kg + 0.9 kg/cm for each cm >152 cm.

Add 10% for a heavy frame; subtract 10% for a light frame.

Definitions

In the AMH, dose recommendations for selected drugs are based on degree of renal impairment. We generally describe 3 categories of impairment, based on creatinine clearance:

• severe impairment, creatinine clearance <10 mL/minute
• moderate impairment, creatinine clearance 10–25 mL/minute
• mild impairment, creatinine clearance 25–50 mL/minute.

Please note, these categories are defined specifically to enable adjustment of drug dosage for patients with renal impairment. They are not designed for other purposes, such as definition and classification of chronic renal diseases. Because of this, our categories may not coincide with other guidelines or classifications.