title: The analytical change in plasma creatinine that constitutes a biologic/physiologic change.
abstract: OBJECTIVE
  Accurate and precise measurements of creatinine are necessary to evaluate changes in kidney function related to a decreased glomerular filtration rate (GFR). When serial measurements of creatinine are monitored in an individual, it is useful to know what magnitude of an analytical change in creatinine indicates a true physiologic/biologic change in plasma creatinine that might warrant clinical intervention.
  
  
  METHODS
  We compared results between three different methods for creatinine using large chemistry analyzers, two based on alkaline picrate (AP1 and AP2), and one based on dry-slide enzymatic conversion (ENZ). On each of three different segments or days of the study spaced 1-2months apart, we selected 10 different plasma samples having creatinine concentrations ranging from about 0.5mg/dL to 4.5mg/dL (44 to 400μmol/L). Each sample was analyzed in triplicate on each of two same-model analyzers at each institution, then from this data we determined the precision of each model of analyzer. The within-instrument precision of each analyzer was evaluated from the differences between the triplicate results on each sample by each analyzer (mean and SD of the differences). The between-instrument precision was evaluated as the differences between results on the same sample (1, 2, 3, etc.) analyzed on different analyzers of the same model (A and B). This between-analyzer precision data was used to determine both the range and mean±2SD of the differences that could be used to indicate that greater changes in creatinine concentrations would represent a biologic change.
  
  
  RESULTS
  The within-instrument precision was best for the ENZ method in comparison to the two alkaline picrate rate methods. The between-instrument precision of the 90 consecutive measurements (30 samples×triplicate analyses) between the same-model analyzers were (mean and SD of differences in mg/dL): -0.018 and 0.029 (ENZ); 0.016 and 0.11 (AP1), and -0.058 and 0.071 (AP2).
  
  
  CONCLUSIONS
  While all three of the creatinine methods studied had good precision, the ENZ method had the best precision, such that a change of 0.07mg/dL (6μmol/L) in serial creatinine concentrations up to 1.5mg/dL on a patient could indicate a biologic change had occurred. For the alkaline picrate methods, a measured change of creatinine of 0.23mg/dL for AP1 or 0.11mg/dL for AP2 would indicate that a physiologic change in serum/plasma creatinine has occurred. While a definite biologic change may simply represent daily variations, detecting a biologic change in creatinine more rapidly could impact the ability of creatinine to detect early and clinically significant changes in renal function.
authors.affiliation: Dept of Pathology and Clinical Laboratories, Duke University Medical Center, Durham, NC 27710, United States. Electronic address: john.toffaletti@duke.edu.
authors.forename: John G
authors.initials: JG
authors.lastname: Toffaletti
authors.affiliation: Dept of Pathology and Laboratory Medicine, UNC, Chapel Hill, NC 27514, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Hammett-Stabler
authors.affiliation: McLendon Clinical Laboratories, UNC Healthcare, Chapel Hill, NC, United States.
authors.forename: Margaret
authors.initials: M
authors.lastname: Gearhart
authors.affiliation: Dept of Biostatistics and Bioinformatics, Duke University Medical Center, United States.
authors.forename: Kingshuk
authors.initials: K
authors.lastname: Roy Choudhury
authors.affiliation: Dept of Pathology and Clinical Laboratories, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Handel
mesh_terms: D003404:Creatinine / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests; D010851:Picrates / Q000737:chemistry
chemical_list: D010851:Picrates; C005858:picric acid; D003404:Creatinine
keywords: Creatinine; Kidney function; Method precision