Renal Function Estimates Journal Club – Richard C. Walls 07/16/2013
Article Title/Citation
BACKGROUND AND OVERVIEW
“Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Enrolled
in the Baltimore Longitudinal Study on Aging: Impact on Renal Drug Dosing”
Thomas C. Dowling, En-Shih Wang, Luigi Ferrucci, John D. Sorkin
PMID: 23625813
Study objectives/purpose
(and research hypothesis, if
applicable)
To evaluate the accuracy of Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD),
and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) by comparing to measured
creatinine clearance by 24-hour urine collection.
Brief background (why
issue is important, summary
of previous literature)
A great number of drugs are eliminated through the kidney and thus must have their dosages adjusted
to avoid toxicity in cases of compromised clearance, and to ensure medications are dosed to therapeutic
levels in the setting of adequate clearance. The majority of drug dosing guidelines are based on CrCl,
and the accuracy of equations estimating this value can have important implications on proper drug
dosing. Additionally, as renal function declines with age, and the number of medications tends to
increase as patients age as well, and older population is especially at risk of being misdosed due to renal
function. NKDEP recommended MDRD be used interchangeably with the CG.
Funding sources
NIH and Baltimore VA Geriatric Research Education and Clinical Center
Study design and
methodology
METHODS
Retrospective analysis of data collected from the Baltimore Longitudinal Study of Aging (BLSA)
database.
Patient selection &
enrollment [inclusion/ exclusion
criteria]
BLSA: Normal community-dwelling volunteers
Included: Age ≥ 70, mClCr < 70, participated in BLSA 01/2005—12/2010
Excluded: Overt signs of renal failure, receiving any form of dialysis
Outcome measures/
endpoints
mClCr, estimated CG CrCl, estimated r-CG CrCl (SCr ≤ 1.0 rounded to 1.0), estimated MDRD GFR,
estimated CKD-EPI GFR.
Dose discordance: reported for 10 drugs, percentage of instances in which the equation would
recommend a different dose than the CG estimate.
Statistical analyses
Enrollment & baseline
characteristics
Summary of primary and
secondary outcomes
including subgroup analysis,
etc. Be sure to include both
efficacy and safety
parameters, if appropriate
Accuracy: within-person difference between estimated value and mClcr. MDRD & CKD-EPI also
compared for their accuracy as the within-person difference between estimated value and CG. Variance
compared using Fisher F test, values reported as mean ± SD, two-tailed p<0.05 considered significant.
RESULTS
N=269: 129 men, 140 women; 85% white
Age 80.7 ± 6.0, SCr 1.12 ± 0.37, Only 28 patients with BMI>30, no patients BMI>40
103 subjects with SCr < 1.0 (8.0 ± 0.1; range 0.44—0.94).
Difference from mClCr
CG: -3.2 ± 14.2 p<0.001;
MDRD: 12.8 ± 17.5 p<0.001; CKD-EPI: 7.1 ± p<0.001
Variance greater for all estimates than for mClCr
mClcr 56.2 ± 11.5; CG 55.8 ±15; r-CG 44.1 ± 10.2
Median dose discordance relative to CG 28.6%, discordance roughly rises as renal impairment worsens
Renal Function Estimates Journal Club – Richard C. Walls 07/16/2013
Brief summary of authors’
main discussion points
Author’s conclusions
Study strengths
AUTHORS’ DISCUSSION & CONCLUSIONS
All estimations of CrCl have some degree of bias from mCl Cr. CG most closely estimates actual
clearance but with a trend toward underestimation and with greater variance. eGFR equations generally
overestimate clearance and result in approximately 25% of dose discordance with CG.
eGFR equations should not be used to determine renal dosing of medications due to their
overestimation of renal clearance. Additionally, the author argues against the practice of rounding S cr to
1.0 for elderly patients with an SCr < 1.0.
STUDENT’S DISCUSSION & CONCLUSIONS
Good comparisons: Gold standard measurement as well as the prevailing equation compared with
alternatives
Reasonable target population: Targeting an aging population makes great sense given the implications of
renal dosing as age advances
Clear difference in groups evident: Statistical significance very clear, but easy to see that there is a
clinical difference in the clearance estimates
Study limitations
Small sample size: not racially diverse, obese population not well accounted for.
Relatively healthy population: would findings be as applicable in setting of active kidney injury?
No real clinical outcomes: Dose discordance statistics interesting, but how many of those discordant
doses would have clinical implications?
Limited data for SCr <1.0 group: What sort of dose discordance?
Applicability and impact
on pharmacists/healthcare
providers
Renal dosing is an everyday element of pharmacy practice, although the limited demographics of the
study population may limit widespread applicability of this trial to multiple patient observations,
however the findings of this trial still bring many important questions to light about the equations we
use to estimate renal function, their correlation to dosage recommendations to patients, and their
ultimate impact on patient outcomes.
Student Conclusions and
recommendations
Remember that all of the equations are estimates and have high variability. Important to integrate
broader clinical picture to this single laboratory finding: trends in Cr, comparison to baseline Cr, actual
clearance of pharmacokinetically monitored drugs, response to other meds that are renally adjusted).
Would second the author’s recommendation that the eGFR equations be avoided as an estimate of CrCl
for dosing purposes, and that the CG ought to be preferred.