Assessing renal function
The extent of accumulation of drugs in renal impairment depends on the degree of dysfunction, the normal route of excretion, and the dose. Before a drug and dose schedule can be chosen, the severity of renal function must be established. To refresh your memory about how the nephron works, watch this short video. |
| Diagram of a nephron Courtesy of Ruth Lawson, Wikimedia Commons |
Renal function is assessed by measuring or estimating glomerular filtration rate (GFR), which reflects the number of functioning glomeruli. The GFR can be estimated by looking at the rate at which the body clears one of its own waste products – creatinine. This is called the creatinine clearance (CrCl). Using serum creatinine to calculate CrCl assumes that renal function and serum creatinine are stable.
The creatinine clearance is calculated as follows, using the Cockcroft-Gault equation:
where F = 1.04 in females and 1.23 in males. Weight should be ideal body weight (IBW) particularly in oedematous patients and patients with ascites. For patients who are obese, IBW can be used but some experts have suggested that an adjustment factor of 40% be applied to the patient’s excess weight over their ideal weight.
The Cockcroft-Gault equation should not be used in children, pregnancy or rapidly changing renal function. Use in patients with low muscle mass may lead to an overestimation of renal function; conversely use in patients with high muscle mass may lead to an underestimation of renal function.
CrCl (mL/min) = F x (140 – age) x (weight in Kg)/plasma creatinine (micromol/L)
The Cockcroft-Gault equation should not be used in children, pregnancy or rapidly changing renal function. Use in patients with low muscle mass may lead to an overestimation of renal function; conversely use in patients with high muscle mass may lead to an underestimation of renal function.
Alternative methods of expressing renal function include the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or the Modification of Diet in Renal Disease (MDRD) formulae to give an estimate of GFR (known as eGFR). There are similarities with the Cockcroft-Gault equation but important differences include the assumption that patients are of average weight and build and so are of average surface area (1.73 square metres).
These equations have limitations similar to the Cockcroft-Gault equation, and should not be used for patients who are at extremes of weight, are pregnant, or for children. In addition the MHRA have advised that eGFR should not be used to calculate the dose for patients taking renally excreted drugs with a narrow therapeutic range, nephrotoxic medicines or direct-acting oral anticoagulants; a CrCl calculated using the Cockcroft-Gault equation should be used.
Actual GFR may be calculated from eGFR using the following equation:
Actual GFR = eGFR x BSA/1.73
The CKD-EPI, MDRD and Cockcroft-Gault equations may produce different estimates of renal function and are not interchangeable. Most published information on drug elimination in renal failure is usually stated in terms of CrCl using the Cockcroft-Gault equation.
In the UK, clinical laboratories should report eGFR and serum creatinine, so that you can calculate the CrCl using the Cockcroft-Gault equation if required.
It is important to remember that the normal process of ageing involves the loss of nephrons and therefore it is reasonable to assume that all elderly patients have some degree of renal impairment.
Plasma urea can be used to estimate renal function but its production is more variable than that of creatinine and is therefore not reliable.
It is important to remember that the normal process of ageing involves the loss of nephrons and therefore it is reasonable to assume that all elderly patients have some degree of renal impairment.
Plasma urea can be used to estimate renal function but its production is more variable than that of creatinine and is therefore not reliable.