title: Measurement Error as Alternative Explanation for the Observation that CrCl/GFR Ratio is Higher at Lower GFR.
abstract: Overestimation of GFR by urinary creatinine clearance (CrCl) at lower levels of GFR has long been attributed to enhanced creatinine secretion. However, this does not take into consideration the contribution of errors in measured GFR (and CrCl) due to short-term biologic variability or test imprecision.
  
  
  
  We analyzed cross-sectional data among 1342 participants from the Chronic Renal Insufficiency Cohort study with baseline measurement of GFR by iothalamate clearance (iGFR) and CrCl by 24-hour urine collection. We examined the CrCl/iGFR ratio classified by categories of iGFR and also by categories of CrCl.
  
  
  
  Overall, mean CrCl/iGFR ratio was 1.13. CrCl/iGFR ratio was higher at lower iGFR categories. In contrast, this ratio was lower at lower CrCl levels. We hypothesize these relationships could be due to measurement error, which is bolstered by replicating these trends in a simulation and modeling exercise in which there was no variation in the ratio of CrCl/iGFR with true kidney function but taking into account the effect of measurement error in both CrCl and iGFR (of magnitudes previously described in the literature). In our simulated data, the observed CrCl/iGFR ratio was higher at lower observed iGFR levels when patients were classified by categories of observed iGFR. When the same patients were classified by categories of observed CrCl, the observed CrCl/iGFR ratio was lower at lower observed CrCl levels.
  
  
  
  The combined empirical and modeling results suggest that measurement errors (in both CrCl and iGFR) should be considered as an alternative explanation for the longstanding observation that the ratio of CrCl to iGFR gets larger as iGFR decreases.
authors.affiliation: Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.|Department of Medicine, and.
authors.forename: Xuehan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCulloch
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Yen-Chung
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Isabel Elaine
authors.initials: IE
authors.lastname: Allen
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Nisha
authors.initials: N
authors.lastname: Bansal
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.|Division of Research, Kaiser Permanente Northern California, Oakland, California; and.|Department of Health Research and Policy, Stanford University, Stanford, California.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Go
authors.affiliation: Department of Medicine, and.|Division of Research, Kaiser Permanente Northern California, Oakland, California; and.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hsu
mesh_terms: D003198:Computer Simulation; D003404:Creatinine / Q000652:urine*; D003430:Cross-Sectional Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007483:Iothalamic Acid / Q000378:metabolism; D007677:Kidney Function Tests; D008954:Models, Biological; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology* / Q000652:urine; D016482:Urinalysis
chemical_list: D007483:Iothalamic Acid; D003404:Creatinine