title: Analysis of risk factors associated with renal function trajectory over time: a comparison of different statistical approaches.
abstract: BACKGROUND
  The most commonly used methods to investigate risk factors associated with renal function trajectory over time include linear regression on individual glomerular filtration rate (GFR) slopes, linear mixed models and generalized estimating equations (GEEs). The objective of this study was to explain the principles of these three methods and to discuss their advantages and limitations in particular when renal function trajectories are not completely observable due to dropout.
  
  
  METHODS
  We generated data from a hypothetical cohort of 200 patients with chronic kidney disease at inclusion and seven subsequent annual measurements of GFR. The data were generated such that both baseline level and slope of GFR over time were associated with baseline albuminuria status. In a second version of the dataset, we assumed that patients systematically dropped out after a GFR measurement of <15 mL/min/1.73 m(2). Each dataset was analysed with the three methods.
  
  
  RESULTS
  The estimated effects of baseline albuminuria status on GFR slope were similar among the three methods when no patient dropped out. When 32.7% dropped out, standard GEE provided biased estimates of the mean GFR slope in normo-, micro- and macroalbuminuric patients. Linear regression on individual slopes and linear mixed models provided slope estimates of the same magnitude, likely because most patients had at least three GFR measurements. However, the linear mixed model was the only method to provide effect estimates on both slope and baseline level of GFR unaffected by dropout.
  
  
  CONCLUSIONS
  This study illustrates that the linear mixed model is the preferred method to investigate risk factors associated with renal function trajectories in studies, where patients may dropout during the study period because of initiation of renal replacement therapy.
authors.affiliation: University of Bordeaux, ISPED, Centre INSERM U897-Epidemiology-Biostatistics, Bordeaux, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Leffondre
authors.affiliation: University of Bordeaux, ISPED, Centre INSERM U897-Epidemiology-Biostatistics, Bordeaux, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Boucquemont
authors.affiliation: CNR-IBIM/IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, Calabria, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.affiliation: Department of Medical Informatics, Academic Medical Center, ERA-EDTA Registry, Amsterdam, Netherlands.
authors.forename: Vianda S
authors.initials: VS
authors.lastname: Stel
authors.affiliation: Medical University of Vienna, Center for Medical Statistics, Informatics and Intelligent Systems, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Heinze
authors.affiliation: Medical University of Vienna, Center for Medical Statistics, Informatics and Intelligent Systems, Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Dunkler
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000503:physiopathology*; D012307:Risk Factors; D013997:Time Factors
keywords: chronic kidney disease; dropout; generalized estimating equations; glomerular filtration rate; linear mixed model