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Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Enrolled in the Baltimore Longitudinal Study on Aging: Impact on Renal Drug Dosing
Author(s) -
Dowling Thomas C.,
Wang EnShih,
Ferrucci Luigi,
Sorkin John D.
Publication year - 2013
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1282
Subject(s) - renal function , medicine , creatinine , kidney disease , dosing , urology , population , estimating equations , dose , mathematics , statistics , maximum likelihood , environmental health
Objectives To evaluate the performance of kidney function estimation equations and to determine the frequency of drug dose discordance in an older population. Design Cross‐sectional analysis of data from community‐dwelling volunteers randomly selected from the B altimore L ongitudinal S tudy of A ging from J anuary 1, 2005, to D ecember 31, 2010. Subjects A total of 269 men and women with a mean ± SD age of 81 ± 6 years, mean serum creatinine concentration ( S cr ) of 1.1 ± 0.4 mg/dl, and mean 24‐hour measured creatinine clearance (m C l cr ) of 53 ± 13 ml/minute. Measurements and Main Results Kidney function was estimated by using the following equations: C ockcroft‐ G ault ( CG ), Modification of D iet in R enal D isease ( MDRD ), and C hronic K idney D isease E pidemiology C ollaboration ( CKD ‐ EP I). The performance of each equation was assessed by measuring bias and precision relative to m C l cr . Dose calculation errors (discordance) were determined for 10 drugs requiring renal dosage adjustments to avoid toxicity when compared with the dosages approved by the Food and Drug Administration. The CG equation was the least biased estimate of mC l cr . The MDRD and CKD ‐ EPI equations were significantly positively biased compared with CG (mean ± SD 34 ± 20% and 22 ± 15%, respectively, p<0.001) and m C l cr (29 ± 47% and 18 ± 40%, respectively, p<0.001). Rounding low S cr values (less than 1.0 mg/dl) up to an arbitrary value of 1.0 mg/dl resulted in CG values (44 ± 10 ml/minute) that were significantly lower than m C l cr (56 ± 12 ml/minute, p<0.001) and CG (56 ± 15 ml/minute, p<0.001). The MDRD and CKD ‐ EPI equations had median dose discordance rates of 28.6% and 22.9%, respectively. Conclusion The MDRD and CKD ‐ EPI equations significantly overestimated creatinine clearance (m C l cr and CG ) in elderly individuals. This leads to dose calculation errors for many drugs, particularly in individuals with severe renal impairment. Thus equations estimating glomerular filtration rate should not be substituted in place of the CG equation in older adults for the purpose of renal dosage adjustments. In addition, the common practice of rounding or replacing low S cr values with an arbitrary value of 1.0 mg/dl for use in the CG equation should be avoided. Additional studies that evaluate alternative e GFR equations in the older populations that incorporate pharmacokinetic and pharmacodynamic outcomes measures are needed.