title: Change in novel filtration markers and risk of ESRD.
abstract: BACKGROUND
  Chronic kidney disease progression is a risk factor for end-stage renal disease (ESRD). A 57% decline in creatinine-based estimated glomerular filtration rate (eGFRcr) is an established surrogate outcome for ESRD in clinical trials, and a 30% decrease recently has been proposed as a surrogate end point. However, it is unclear whether change in novel filtration marker levels provides additional information for ESRD risk to change in eGFRcr.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Atherosclerosis Risk in Communities (ARIC) Study participants from 4 US communities.
  
  
  METHODS
  Percent change in levels of filtration markers (eGFRcr, cystatin C-based eGFR [eGFRcys], the inverse of β2-microglobulin concentration [1/B2M]) over a 6-year period.
  
  
  RESULTS
  Incident ESRD.
  
  
  METHODS
  Cox proportional hazards regression with adjustment for demographics, kidney disease risk factors, and first measurement of eGFRcr.
  
  
  RESULTS
  During a median follow-up of 13 years, there were 142 incident ESRD cases. In adjusted analysis, declines > 30% in eGFRcr, eGFRcys, and 1/B2M were associated significantly with ESRD compared with stable concentrations of filtration markers (HRs of 19.96 [95% CI, 11.73-33.96], 16.67 [95% CI, 10.27-27.06], and 22.53 [95% CI, 13.20-38.43], respectively). Using the average of declines in the 3 markers, >30% decline conferred higher ESRD risk than that for eGFRcr alone (HR, 31.97 [95% CI, 19.40-52.70; P=0.03] vs eGFRcr).
  
  
  CONCLUSIONS
  Measurement error could influence estimation of change in filtration marker levels.
  
  
  CONCLUSIONS
  A >30% decline in kidney function assessed using novel filtration markers is associated strongly with ESRD, suggesting the potential utility of measuring change in cystatin C and B2M levels in settings in which improved outcome ascertainment is needed, such as clinical trials.
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. Electronic address: crebhol1@jhu.edu.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Rebholz
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Grams
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
mesh_terms: D015415:Biomarkers; D015897:Comorbidity; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000209:etiology; D007677:Kidney Function Tests / Q000379:methods*; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology; D001613:beta 2-Microglobulin / Q000032:analysis*
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D001613:beta 2-Microglobulin; D003404:Creatinine
keywords: chronic kidney disease (CKD); creatinine; cystatin C; disease progression; end-stage renal disease (ESRD); filtration marker; kidney disease outcome; surrogate endpoint; β(2)-Microglobulin (B2M)