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BACKGROUND AND OVERVIEWArticle Title/Citation“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. SorkinPMID: 23625813Study 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 sourcesNIH and Baltimore VA Geriatric Research Education and Clinical CenterMETHODSStudy design and methodologyRetrospective analysis of data collected from the Baltimore Longitudinal Study of Aging (BLSA) database.Patient selection & enrollment [inclusion/ exclusion criteria]BLSA: Normal community-dwelling volunteersIncluded: Age ≥ 70, mClCr < 70, participated in BLSA 01/2005—12/2010Excluded: Overt signs of renal failure, receiving any form of dialysisOutcome measures/ endpointsmClCr, 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 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.RESULTSEnrollment & baseline characteristicsN=269: 129 men, 140 women; 85% whiteAge 80.7 ± 6.0, SCr 1.12 ± 0.37, Only 28 patients with BMI>30, no patients BMI>40103 subjects with SCr < 1.0 (8.0 ± 0.1; range 0.44—0.94). Summary of primary and secondary outcomes including subgroup analysis, etc. Be sure to include both efficacy and safety parameters, if appropriateDifference from mClCrCG: -3.2 ± 14.2 p<0.001;MDRD: 12.8 ± 17.5 p<0.001; CKD-EPI: 7.1 ± p<0.001Variance greater for all estimates than for mClCrmClcr 56.2 ± 11.5; CG 55.8 ±15; r-CG 44.1 ± 10.2Median dose discordance relative to CG 28.6%, discordance roughly rises as renal impairment worsensAUTHORS’ DISCUSSION & CONCLUSIONSBrief summary of authors’ main discussion pointsAll estimations of CrCl have some degree of bias from mClCr. 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. Author’s conclusionseGFR 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 Scr to 1.0 for elderly patients with an SCr < 1.0.STUDENT’S DISCUSSION & CONCLUSIONSStudy strengths Good comparisons: Gold standard measurement as well as the prevailing equation compared with alternativesReasonable target population: Targeting an aging population makes great sense given the implications of renal dosing as age advancesClear difference in groups evident: Statistical significance very clear, but easy to see that there is a clinical difference in the clearance estimatesStudy limitationsSmall 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. ................
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