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How To Adjust Drug Doses in Chronic Kidney Disease
How To Adjust Drug Doses in Chronic Kidney Disease
ARTICLE
creatinine is an end product of muscle breakdown, filtration markers.7 It incorporates age and sex into a
each formula allows for the serum creatinine relatively complicated formula. These demographics
concentration to be adjusted for body mass based on are known at the time of blood collection so the
patient characteristics. eGFR is automatically calculated and reported by the
The Cockcroft-Gault formula estimates creatinine laboratory. The units for the automated eGFR are
clearance (eCrCl) and incorporates age, sex and body mL/min/1.73 m2 and it is now an accepted method
weight (Box 1).6 Because eCrCl was validated against for the classification and monitoring of chronic kidney
measured CrCl based on 24-hour urine collection, it disease (Table 1).8,9
overestimates the actual GFR given that creatinine The initial report describing the CKD-EPI formula
is both filtered and secreted in the nephron tubules. did not observe an effect of age or body mass index
The usual units for eCrCl are mL/minute and multiple (BMI) on the accuracy of its prediction.7 However, it
online calculators are available. However, by 2010 should be noted that the initial report was based on
most laboratories in Australia were using a newer a population who were mostly younger than 66 years
creatinine assay standardised to isotope dilution mass old with a mean body surface area of 1.90–1.93 m2
spectrometry (IDMS) which resulted in a 10–20% and a BMI of 27–28 kg/m2 (mean height 170 cm,
decrease in creatinine concentrations. This, in turn, mean weight 79–82 kg). The automated eGFR
will increase the eCrCl compared to what would have may not therefore apply to patients with different
been calculated pre-2010. demographics. Since the body surface area for most
patients is higher than 1.73 m2, the actual GFR in such
The CKD-EPI formula estimates GFR because it was
a patient will be higher than that reported by the
validated against GFR measured using exogenous
laboratory. The eGFR can be de-indexed (converted
to actual mL/min) by multiplying the automated eGFR
by the patient’s body surface area (m2) and then
Table 1 R
elationship between glomerular filtration rate and
stage of chronic kidney disease* dividing by 1.73 (see Box 1).
Measured GFR
Kidney function stage eGFR (mL/min/1.73 m2)
The mGFR is determined after giving an exogenous
1 ≥90
filtration marker, such as 51Cr-EDTA, 125I-iothalamate,
2 60–89 DTPA or MAG3. It is the most reliable method of
quantifying GFR because these markers are filtered
3a 45–59
and not substantially secreted into or reabsorbed
3b 30–44 from the nephron. The mGFR can be indexed by
4 15–29 adjusting for a standard body surface area of 1.73 m2.
ARTICLE
Reduced GFR May be less accurate May be more accurate Automated eGFR is an adequate measure of kidney
function for drug dosing in most cases, but there are
Actual BSA >1.73 m2 Depends on body Actual GFR is >30% notable exceptions requiring further consideration.
weight only, height is not higher for taller or Dose adjustment in chronic kidney disease always
incorporated heavier individuals
requires decision making on a case-by-case basis.
Older age (>70 years) Acceptable Acceptable Alternative laboratory methods for guiding drug
dosing are being researched, such as tests based on
Younger age (<40 years) May be less accurate May be more accurate cystatin C, and may have a useful role in the future.
Obesity (e.g. BMI >30 kg/m2) Overestimates GFR, use Underestimates GFR, use
Darren Roberts is the Chair of the Editorial Executive
or weight >120 kg adjusted ideal body weight de-indexed eGFR
Committee of Australian Prescriber.
BMI <18.5 kg/m2 or weight Acceptable, use actual Overestimates GFR, use
<60 kg body weight de-indexed eGFR Acknowledgement: Darren Roberts acknowledges
support of the Clinician ‘Buy-Out’ Program, St Vincent’s
eCrCl is estimated creatinine clearance as determined by the Cockcroft-Gault formula. Centre for Applied Medical Research.
The formula was validated against a 24-hour creatinine clearance and the units are
mL/min. Actual body weight is commonly used in the calculations. The eCrCl is usually
higher than the actual GFR.
eGFR is the estimated glomerular filtration rate as determined by the CKD-EPI formula.
The formula was validated against a measured glomerular filtration rate and the units
are mL/min/1.73 m2 body surface area.
BSA body surface area
BMI body mass index
GFR glomerular filtration rate
ARTICLE
REFERENCES
1. Australian Bureau of Statistics. National health survey: 10. Michels WM, Grootendorst DC, Verduijn M, Elliott EG,
first results, 2017-18. ABS Catalogue No. 4364.0.55.001. Dekker FW, Krediet RT. Performance of the Cockcroft-Gault,
https://www.abs.gov.au/AUSSTATS/[email protected]/ MDRD, and new CKD-EPI formulas in relation to GFR, age,
DetailsPage/4364.0.55.0012017-18 [cited 2019 Sep 1] and body size. Clin J Am Soc Nephrol 2010;5:1003-9.
2. Australian Bureau of Statistics. Australian health survey: https://doi.org/10.2215/CJN.06870909
biomedical results for chronic diseases, 2011-12. ABS 11. Delanaye P, Guerber F, Scheen A, Ellam T, Bouquegneau A,
Catalogue No. 4364.0.55.005. https://www.abs.gov.au/ Guergour D, et al. Discrepancies between the Cockcroft-
AUSSTATS/[email protected]/DetailsPage/4364.0.55.0052011-12 Gault and Chronic Kidney Disease Epidemiology (CKD-EPI)
[cited 2019 Sep 1] equations: implications for refining drug dosage adjustment
3. Ko S, Venkatesan S, Nand K, Levidiotis V, Nelson C, Janus E. strategies. Clin Pharmacokinet 2017;56:193-205.
International statistical classification of diseases and related https://doi.org/10.1007/s40262-016-0434-z
health problems coding underestimates the incidence and 12. Dowling TC, Wang ES, Ferrucci L, Sorkin JD. Glomerular
prevalence of acute kidney injury and chronic kidney disease filtration rate equations overestimate creatinine
in general medical patients. Intern Med J 2018;48:310-5. clearance in older individuals enrolled in the Baltimore
https://doi.org/10.1111/imj.13729 Longitudinal Study on Aging: impact on renal drug dosing.
4. Roberts DM, Sevastos J, Carland JE, Stocker SL, Lea‑Henry TN. Pharmacotherapy 2013;33:912-21. https://doi.org/10.1002/
Clinical pharmacokinetics in kidney disease: application to phar.1282
rational design of dosing regimens. Clin J Am Soc Nephrol 13. Björk J, Grubb A, Gudnason V, Indridason OS, Levey AS,
2018;13:1254-63. https://doi.org/10.2215/CJN.05150418 Palsson R, et al. Comparison of glomerular filtration rate
5. Lea-Henry TN, Carland JE, Stocker SL, Sevastos J, estimating equations derived from creatinine and cystatin C:
Roberts DM. Clinical pharmacokinetics in kidney disease: validation in the Age, Gene/Environment Susceptibility-
fundamental principles. Clin J Am Soc Nephrol Reykjavik elderly cohort. Nephrol Dial Transplant
2018;13:1085-95. https://doi.org/10.2215/CJN.00340118 2018;33:1380-8. https://doi.org/10.1093/ndt/gfx272
6. Cockcroft DW, Gault MH. Prediction of creatinine clearance 14. Chew-Harris JS, Chin PK, Florkowski CM, George P, Endre Z.
from serum creatinine. Nephron 1976;16:31-41. Removal of body surface area normalisation improves
https://doi.org/10.1159/000180580 raw-measured glomerular filtration rate estimation by
7. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, the Chronic Kidney Disease Epidemiology Collaboration
Feldman HI, et al.; CKD-EPI (Chronic Kidney Disease equation and drug dosing in the obese. Intern Med J
Epidemiology Collaboration). A new equation to estimate 2015;45:766-73. https://doi.org/10.1111/imj.12791
glomerular filtration rate. Ann Intern Med 2009;150:604-12. 15. Bouquegneau A, Vidal-Petiot E, Moranne O, Mariat C, Boffa JJ,
https://doi.org/10.7326/0003-4819-150-9-200905050-00006 Vrtovsnik F, et al. Creatinine-based equations for the adjustment
8. Ludlow M, Jesudason S, Johnson DW. Automatic reporting of drug dosage in an obese population. Br J Clin Pharmacol
of estimated glomerular filtration rate in Australia turns 13: 2016;81:349-61. https://doi.org/10.1111/bcp.12817
re-examining the impact. Med J Aust 2018;209:244-5. 16. Matzke GR, Aronoff GR, Atkinson AJ Jr, Bennett WM,
https://doi.org/10.5694/mja18.00544 Decker BS, Eckardt KU, et al. Drug dosing consideration in
9. Johnson DW, Jones GR, Mathew TH, Ludlow MJ, Doogue MP, patients with acute and chronic kidney disease-a clinical
Jose MD, et al.; Australasian Creatinine Consensus Working update from Kidney Disease: Improving Global Outcomes
Group. Chronic kidney disease and automatic reporting (KDIGO). Kidney Int 2011;80:1122-37. https://doi.org/10.1038/
of estimated glomerular filtration rate: new developments ki.2011.322
and revised recommendations. Med J Aust 2012;197:224-5.
https://doi.org/10.5694/mja11.11329