title: GFR may not accurately predict aspects of proximal tubule drug handling.
abstract: OBJECTIVE
  Dose modification in renal impairment has traditionally been based on changes in estimated glomerular filtration rate (eGFR; estimated by creatinine clearance). However, many drugs are eliminated by tubular anionic and cationic transport where changes in eGFR may not necessarily reflect changes in tubular function. This study investigated the relationship between GFR and renal tubular function with reference to drug handling by using accepted drug probes.
  
  
  METHODS
  Three drug probes, (51)Cr-EDTA, fluconazole, and pindolol, were administered to patients who had varying degrees of renal impairment. Blood sampling, assays, and a pharmacokinetic analysis were performed for all drug probes and endogenous urate. Measured GFR ((51)Cr-EDTA clearance; mGFR) was compared to tubular anionic transport (urate clearance), tubular reabsorption (fluconazole clearance), and tubular cationic transport (S-pindolol clearance).
  
  
  RESULTS
  A moderately strong association was demonstrated between the measured isotopic GFR and creatinine clearance (R(2) = 0.78). A moderate positive correlation was found between mGFR and proximal tubular anion transport and reabsorption (R(2) = 0.40-0.44, p < 0.0001). In contrast, cationic secretion correlated poorly with mGFR (R(2) = 0.11, p = 0.036).
  
  
  CONCLUSIONS
  Given that drug dosing schedules utilise eGFR values as the basis for modifying drug dosing, our results would suggest that a recommendation of a dose reduction according to eGFR alone should be treated with caution.
authors.affiliation: Department of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: T L
authors.initials: TL
authors.lastname: Putt
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
authors.forename: J B W
authors.initials: JB
authors.lastname: Schollum
authors.forename: R J
authors.initials: RJ
authors.lastname: Walker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000493:pharmacokinetics; D005260:Female; D015725:Fluconazole / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests / Q000379:methods; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000493:pharmacokinetics; D051437:Renal Insufficiency / Q000503:physiopathology*
chemical_list: D015725:Fluconazole; D004492:Edetic Acid; D010869:Pindolol