title: The eGFR-C study: accuracy of glomerular filtration rate (GFR) estimation using creatinine and cystatin C and albuminuria for monitoring disease progression in patients with stage 3 chronic kidney disease--prospective longitudinal study in a multiethnic population.
abstract: BACKGROUND
  Uncertainty exists regarding the optimal method to estimate glomerular filtration rate (GFR) for disease detection and monitoring. Widely used GFR estimates have not been validated in British ethnic minority populations.
  
  
  METHODS
  Iohexol measured GFR will be the reference against which each estimating equation will be compared. The estimating equations will be based upon serum creatinine and/or cystatin C. The eGFR-C study has 5 components: 1) A prospective longitudinal cohort study of 1300 adults with stage 3 chronic kidney disease followed for 3 years with reference (measured) GFR and test (estimated GFR [eGFR] and urinary albumin-to-creatinine ratio) measurements at baseline and 3 years. Test measurements will also be undertaken every 6 months. The study population will include a representative sample of South-Asians and African-Caribbeans. People with diabetes and proteinuria (ACR ≥30 mg/mmol) will comprise 20-30% of the study cohort.2) A sub-study of patterns of disease progression of 375 people (125 each of Caucasian, Asian and African-Caribbean origin; in each case containing subjects at high and low risk of renal progression). Additional reference GFR measurements will be undertaken after 1 and 2 years to enable a model of disease progression and error to be built.3) A biological variability study to establish reference change values for reference and test measures.4) A modelling study of the performance of monitoring strategies on detecting progression, utilising estimates of accuracy, patterns of disease progression and estimates of measurement error from studies 1), 2) and 3).5) A comprehensive cost database for each diagnostic approach will be developed to enable cost-effectiveness modelling of the optimal strategy.The performance of the estimating equations will be evaluated by assessing bias, precision and accuracy. Data will be modelled as a linear function of time utilising all available (maximum 7) time points compared with the difference between baseline and final reference values. The percentage of participants demonstrating large error with the respective estimating equations will be compared. Predictive value of GFR estimates and albumin-to-creatinine ratio will be compared amongst subjects that do or do not show progressive kidney function decline.
  
  
  CONCLUSIONS
  The eGFR-C study will provide evidence to inform the optimal GFR estimate to be used in clinical practice.
  
  
  BACKGROUND
  ISRCTN42955626.
authors.affiliation: Clinical Biochemistry, East Kent Hospitals University NHS Foundation Trust, Canterbury, Kent CT1 3NG, UK. elamb@nhs.net.
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Lamb
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Brettell
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.forename: Neil
authors.initials: N
authors.lastname: Dalton
authors.forename: Jon J
authors.initials: JJ
authors.lastname: Deeks
authors.forename: Kevin
authors.initials: K
authors.lastname: Harris
authors.forename: Tracy
authors.initials: T
authors.lastname: Higgins
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kalra
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Khunti
authors.forename: Fiona
authors.initials: F
authors.lastname: Loud
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Ottridge
authors.forename: Claire C
authors.initials: CC
authors.lastname: Sharpe
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Sitch
authors.forename: Paul E
authors.initials: PE
authors.lastname: Stevens
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sutton
authors.forename: Maarten W
authors.initials: MW
authors.lastname: Taal
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000175:diagnosis* / Q000208:ethnology*; D015984:Causality; D015897:Comorbidity; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis* / Q000208:ethnology*; D015203:Reproducibility of Results; D012107:Research Design; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D055316:Cystatin C; D003404:Creatinine