title: Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations.
abstract: BACKGROUND
  Kidney disease alters the pharmacokinetic disposition of many medications, requiring dosage adjustment to maintain therapeutic serum concentrations. The Cockcroft-Gault (CG) equation is used for pharmacokinetic studies and drug dosage adjustments, but the Modification of Diet in Renal Disease (MDRD) Study equation is more accurate and more often reported by clinical laboratories than the CG equation.
  
  
  METHODS
  Diagnostic test study.
  
  
  METHODS
  Pooled data set for 5,504 participants from 6 research studies and 4 clinical populations with measured glomerular filtration rate (GFR).
  
  
  METHODS
  Estimated kidney function using the MDRD Study and CG equations incorporating actual (CG) or ideal body weight (CG(IBW)) and standardized serum creatinine concentrations.
  
  
  METHODS
  Measured GFR assessed by using iodine-125-iothalamate urinary clearance.
  
  
  RESULTS
  Concordance of assigned kidney function categories designated by the Food and Drug Administration (FDA) Guidance for Industry for pharmacokinetic studies and recommended dosages of 15 medications cleared by the kidneys.
  
  
  RESULTS
  Concordance of kidney function estimates with measured GFR for FDA-assigned kidney function categories was 78% for the MDRD Study equation compared with 73% for the CG equation (P < 0.001) and 66% for the CG(IBW) equation (P < 0.001). Concordance between the MDRD Study equation and CG and CG(IBW) equations was 78% and 75%, respectively (P < 0.001). Concordance of kidney function estimates with measured GFR for recommended drug dosages was 88% for MDRD Study equation compared with 85% for the CG equation (P < 0.001) and 82% for the CG(IBW) equation (P < 0.001), with lower concordance when dosing recommendations for drugs included narrow GFR ranges. Concordance rates between the CG and CG(IBW) equations and MDRD Study equation were 89% and 88%, respectively (P < 0.05).
  
  
  CONCLUSIONS
  Results based on simulation rather than pharmacokinetic studies. Outcome was drug dosage recommendations, rather than observed drug efficacy and safety.
  
  
  CONCLUSIONS
  The MDRD Study equation can also be used for pharmacokinetic studies and drug dosage adjustments. As more accurate GFR-estimating equations are developed, they should be used for these purposes.
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, MA 02111, USA. lstevens1@tuftsmedicalcenter.org
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Stevens
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Nolin
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Richardson
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.forename: Julia B
authors.initials: JB
authors.lastname: Lewis
authors.forename: Roger
authors.initials: R
authors.lastname: Rodby
authors.forename: Raymond
authors.initials: R
authors.lastname: Townsend
authors.forename: Aghogho
authors.initials: A
authors.lastname: Okparavero
authors.forename: Yaping Lucy
authors.initials: YL
authors.lastname: Zhang
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Schmid
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000097:blood; D054796:Drug Dosage Calculations; D004345:Drug Industry / Q000592:standards; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006287:Health Planning Guidelines; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D003404:Creatinine