title: The impact of pre-intervention rate of kidney function change on the assessment of CKD progression.
abstract: BACKGROUND
  Without a run-in phase, chronic kidney disease (CKD) patients enrolled in clinical trials may not be identified as having progressive disease. The aim of this analysis was to quantify the effects of a run-in phase on kidney function outcome in CKD patients enrolled in the Lipid Lowering and Onset of Renal Disease (LORD) trial.
  
  
  METHODS
  The LORD trial assessed the effects of atorvastatin on the rate of change in the estimated glomerular filtration rate (eGFR) and included patients with serum creatinine 120 μmol/l. In this post hoc analysis, we assessed eGFR change during the 12-month period prior to enrolment, the 3-month run-in phase and the first 12-month period of the trial. Eighty of the original 132 patients (where retrospective data were available) were included. The rate of eGFR change during each period was compared.
  
  
  RESULTS
  Overall kidney function decreased during the 12 months prior to enrolment by (mean, SD) 0.39 ± 0.98 ml/min/1.73 m(2)/month, improved during the 3-month run-in phase by 0.48 ± 2.90 ml/min/1.73 m(2)/month and decreased during the first 12 months of the trial by 0.15 ± 0.57 ml/min/1.73 m(2)/month. However, only 39 % of patients had declining eGFR during the 12 months prior, 19 % in the 3-month run-in and 42 % during the first 12-month study phase.
  
  
  CONCLUSIONS
  Most patients (>60 %) entering this clinical trial had stable or improving kidney function. Enrolment was associated with further improved kidney function, which may have been due to 'regression to the mean' or to the Hawthorne effect. Investigators should include a run-in period to establish the presence of eGFR decline to use as an inclusion criterion in clinical trials assessing this measure of CKD progression.
authors: The University of Queensland, Brisbane, QLD, Australia, rfassett@mac.com.
authors: Robert G
authors: RG
authors: Fassett
authors: Dominic P
authors: DP
authors: Geraghty
authors: Jeff S
authors: JS
authors: Coombes
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011758:Pyrroles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012107:Research Design; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D003404:Creatinine